Academic Membership

Research Description:

Polymeric biomaterials, drug delivery, targeted diagnostics

Keywords:

intracranial drug delivery, neurosurgery, neuroscience

Recent Publications:

Abdullah KG, Lubelski D, Miller J, Steinmetz MP, Shin JH, Krishnaney A, Mroz TE, Benzel EC. Progression free survival and functional outcome after surgical resection of intramedullary ependymomas. J Clin Neurosci. 2015 Dec;22(12):1933-7

Abdullah KG, Rammayya A, Thawani JP, Macyszyn L, O’Rourke DM, Brem S. Factors associated with increased survival after surgical resection of glioblastoma in octogenarians. PLOS One, PLoS One. 2015 May 15;10(5):e0127202. doi: 10.1371/journal.pone.0127202. eCollection 2015

Abdullah KG, Lubelski D, Nucifora P, Brem. The use of diffusion tensor imaging in glioma resection. Neurosurgical Focus. 2013 Apr;34(4):E1

Xiao R, Abdullah KG, Miller JA, Lubelski D, Steinmetz MP, Shin JH, Krishnaney AA, Mroz TE, Benzel EC. Molecular and clinical prognostic factors for favorable outcome following surgical resection of adult intramedullary spinal cord astrocytomas.. Clin Neurol Neurosurg. 2016 Mar 14;144:82-87

Goel N, Abdullah KG, Chen SS. Outcomes and prognostic factors in pediatric oligodendroglioma: a population based study. Pediatric Neurosurgery. 2017 Nov 2.

Chan NK, Abdullah KG, Lubelski D, Steinmetz MP, Benzel EC, Shin JH, Mroz TE. Stereotactic Radiosurgery for Metastatic Spine Tumors. Journal of Neurosurgical Sciences. 2014 Mar;58(1):37-44.

Thawani JP, Singh N, Pisapia JM, Abdullah KG, Parker D, Pukenas BA, Zager E,Verma R, Brem S. Three-Dimensional Printed Modeling of Diffuse Low-Grade Gliomas and Associated White Matter Tract Anatomy. Neurosurgery. 2017. Mar 16

Thawani JP, Ramayya AG, Pisapia JM, Abdullah KG, Lee JY, Grady MS. Operative Strategies to Minimize Complications Following Resection of Pituitary Macroadenomas. J Neurol Surg B Skull Base. 2017 Apr;78(2):184-190.

Lubelski D, Abdullah KG, Weil RJ, Marko NF. Bevacizumab for Radiation Necrosis Following Treatment of High Grade Glioma: A Systematic Review of the Literature. Journal of Neuro-Oncology. 2013 Dec;115(3):317-22.

Keywords:

Targeted Therapy, Antibody and Protein-Based Therapeutics, Intracellular delivery

Research Description:

The Alvarez Research group is working on several drug delivery technologies that align very well with the CT3N mission. At present, we are collaborating with Cesar de la Fuente (a member and UPenn faculty) on the adaptation of one of our technologies, namely foam drug delivery, to target bacterial cells in the body. Our group has recently published several papers on foam technology for treating pleural effusion that might be of interest to the CT3N community. Furthermore, we are developing some novel hydrogels for hydrophobic drug delivery. Overall, the Alvarez Research group would benefit greatly from the symposium series sponsored by CT3N and discussions with its members on current research problems.

Keywords:

Complex fluid rheology, intravenous drug delivery, pleural effusion, pleurodesis, transport phenomena, interfacial transport and rheology, hydrophobic drug delivery, associating polymers, self-assembly

Recent Publications:

TN Beck, AY Deneka, L Chai, C Kanach, P Johal, NJ Alvarez, Y Boumber, EA Golemis, GW Laub: An improved method of delivering a sclerosing agent for the treatment of malignant pleural effusion, BMC Cancer, 2019, (1), 614

J Baxter, TA Lima, R Huneke, CJ Kanach, P Johal, E Reimold, NJ Alvarez, GW Laub: The efficacy of hydrogel foams in talc Pleurodesis, Journal of Cardiothoracic Surgery 15, 1-8

Lavenia J Thursch, David DiGuiseppi, Todd R Lewis, Reinhard Schweitzer-Stenner, Nicolas J Alvarez: Exploring the gel phase of cationic glycylalanylglycine in ethanol/water. I. Rheology and microscopy studies. Journal of Colloid and Interface Science, Volume 564, 22 March 2020, Pages 499-509

David M DiGuiseppi, Lavenia Thursch, Nicolas J Alvarez, Reinhard Schweitzer-Stenner: Exploring the gel phase of cationic glycylalanylglycine in ethanol/water. II. Spectroscopic, kinetic and thermodynamic studies. Journal of Colloid and Interface Science, Volume 573, 1 August 2020, Pages 123-134

S. Farrell, D DiGuiseppi, N Alvarez, R Schweitzer-Stenner: The interplay of aggregation, fibrillization and gelation of an unexpected low molecular weight gelator: glycylalanylglycine in ethanol/water, Soft Matter 12 (28), 6096-6110, 2016

D. DiGuiseppi, J. Kraus, S.E. Toal, NJ Alvarez, R. Schweitzer-Stenner, Investigating the Formation of a Repulsive Hydrogel of a Cationic 16mer Peptide at Low Ionic Strength in Water by Vibrational Spectroscopy and Rheology, The Journal of Physical Chemistry B 120, 10079-10090, 2016

Research Description:

drug delivery, immunotherapy, cellular therapy

Keywords:

CD47, checkpoint blockade, macrophage, immunotherapy

Research Description:

CHOP link: https://www.chop.edu/doctors/bernt-kathrin-m

I am interested in understanding molecular mechanisms of leukemogenesis and drug development in the transcription/epigenetics space. I have recently developed an interest into intrinsically disordered domains, which are playing a key role in transcription control and malignant transformation, but will be very challenging to target. Th CT3N community will be a fantastic community for me to learn more about current cutting edge approaches in drug design and delivery, and to hopefully find collaborators for translational projects.

Keywords:

leukemia, transcription, epigenetics, drug delivery

Recent Publications:

Bernt KM*, Zhu N*, Sinha AU*, Vempati S, Faber J, Krivtsov AV, Feng Z, Punt N, Daigle A, Bullinger L, Pollock R, Richon V, Kung AL*, Armstrong SA*. MLL-rearranged leukemia is dependent on aberrant H3K79 methylation by Dot1l. Cancer Cell. 2011; 20(1):66-78. PMCID: PMC3329803

Daigle SR, Olhava EJ, Therkelsen CA, Majer CR, Sneering CJ, Song J, Johnston D, Porter Scott M, Smith JJ, Xiao Y, Jin L, Kuntz KW, Chesworth R, Moyer MP, Bernt KM, Armstrong SA, Copeland RA, Richon VM, Pollock RM. Selective killing of mixed lineage leukemia cells by a potent small-molecule DOT1L inhibitor. Cancer Cell. 2011; 20(1):53-65. PMCID: PMC4046888

Riedel SS, Haladyna J, Bezzant M, Stevens B, Pollyea DA, Sinha AU, Armstrong SA, Wei Q, Pollock RM, Daigle SR, Jordan CT, Ernst P, Neff T* and Bernt KM*. The histone methyltransferases MLL and DOT1L cooperate with Meningioma-1 to induce AML. J Clin Invest. 2016 Apr 1;126(4):1438-50. PMCID: PMC4811120

Lee S, Liu H, Hong X, Liu X, Crawford F, Zhang Q, Kingsley M, Chen Z, Lengeling A, Bernt K, Marrack P, Kappler J, Hansen K, Zhou Q, Li QY, Zhang G. JMJD6 cleaves MePCE to Release pTEFb. eLife 2020; 9:e53930. PMCID: PMC7064345

Kingsley MC, Xie HM, Riedel SS, Pastuer T, Shank T, Bollig M, Stabler S, Libbrecht C, Deshpande A, Intlekofer A, and Bernt KM. Specific patterns of H3K79 methylation influence genetic interaction of oncogenes in AML. In press, Blood Advances 2020

Danis E, Yamauchi T, Echanique K, Zhang X, Haladyna J, Riedel SS, Zhu N, Xie H, Orkin SH, Armstrong SA, Bernt KM* and Neff T*. Ezh2 controls an early hematopoietic program and growth and survival signaling in early T-Cell precursor acute lymphoblastic leukemia. Cell Reports 2016, Mar 1;14(8):1953-65. PMCID PMC4790111

Lenard A, Xie HM, Riedel S, Yuan ZF, Zhu N, Neff T, Bernt KM. Epigenetic regulation of protein translation in KMT2A-rearranged AML. BioRxiv 2019 DOI: 10.1101/790287, in press in Experimental Hematology, 2020

Research Description:

Development of targeted therapeutics in epigenetics and cancer biology

Keywords:

Chemical Biology, Protein Degradation, Cancer Therapeutics

Recent Publications:

1. Lead-Oriented Synthesis of Epigenetic Relevant Scaffolds, T. Maujean, P. Kannaboina, A.I. Green and G.M. Burslem, Chemical Communications, 2023, DOI: 10.1039/D3CC04317G

2. Regulation of eDHFR-tagged proteins with trimethoprim PROTACs, J.M. Etersque, I.K. Lee, N. Sharma, K.Xu, A. Ruff, J.D. Northrup, S.Sarkar, T Nguyen, R. Lauman, G.M. Burslem and M.A. Sellmyer, Nature Communications, 2023, DOI: 10.1038/s41467-023-42820-3

3. RAB27B Controls Palmitoylation Dependent NRAS Trafficking and Signaling in Leukemia, J. Ren, B.Xing, R.A. O’Keefe, K. Lv, R.Wang, K.M. Bauer, A.Ghazaryan, G.M. Burslem, J. Zhang, R.M. O’Connell, V. Pillai, E.O. Hexner, Mark R. Philips, and W.Tong, Journal of Clinical Investigation, 2023, DOI: 10.1172/JCI165510

4. Photochemical Synthesis of an Epigenetic Focused Tetrahydroquinoline Library, A.I. Green and G.M. Burslem, RSC Medicinal Chemistry, 2021, DOI: 10.1039/D1MD00193K

5. Focused Libraries for Epigenetic Drug Discovery: The Importance of Isosteres, A.I. Green and G.M. Burslem, J. Med. Chem, 2021, 64, 7231-7240

6. Scaffold hopping enables direct access to more potent PROTACs with in vivo activity, G.M. Burslem*, D.P. Bondeson and C.M. Crews*, Chem.Commun., 2020, 56, 6890 (*Co-corresponding authors)

7. Proteolysis Targeting Chimeras as Therapeutics and Tools for Biological Discovery, G.M. Burslem and C.M. Crews, Cell, 2020, 181, 102

8. Targeting BCR-ABL1 in Chronic Myeloid Leukemia by PROTAC-mediated Targeted Protein Degradation, G.M. Burslem, A. Reister-Schultz, D.P. Bondeson, C. Eide, S. Savage, B. Druker and C.M. Crews, Cancer Research, 2019, 79. 4744

9. Enhancing Antiproliferative Activity and Selectivity of a FLT-3 Inhibitor by Proteolysis Targeting Chimera Conversion, G.M. Burslem, J. Song, X. Chen, J. Hines and C.M. Crews, J. Am. Chem. Soc., 2018, 140, 16428

10. Efficient Synthesis of Immunomodulatory Drug Analogues Enables Exploration of Structure Degradation Relationships. G.M. Burslem*, P. Ottis, S. Jaime-Figueroa, A. Morgan, P.M. Cromm, M. Toure and C.M. Crews*, ChemMedChem, 2018, 12, 1508 (*Co-corresponding authors)

Research Description:

Nanoscience, nanotribology (friction, adhesion, lubrication, wear of materials), nanomechanics, scanning probe microscopy. All with relevance to human tissues, cells, orthopedic implants, and soft materials including hydrogels.

Keywords:

Nanotribology, friction, adhesion, lubrication, wear, surfaces, interfaces, nanomechanics, scanning probe microscopy, cell nanomechanics, orthopedic implants, biotribology, soft matter, hydrogels

Recent Publications:

Nanomechanics of pH-Responsive, Drug-Loaded, Bilayered Polymer Grafts. PC Nalam, HS Lee, N Bhatt, RW Carpick, DM Eckmann, RJ Composto. ACS applied materials & interfaces 9 (15), 12936-12948

Nano-rheology of hydrogels using direct drive force modulation atomic force microscopy. PC Nalam, NN Gosvami, MA Caporizzo, RJ Composto, RW Carpick. Soft Matter 11 (41), 8165-8178

Direct torsional actuation of microcantilevers using magnetic excitation. NN Gosvami, PC Nalam, AL Exarhos, Q Tam, JM Kikkawa, RW Carpick. Applied Physics Letters 105 (9), 093101

Transformations in wrinkle patterns: cooperation between nanoscale cross-linked surface layers and the submicrometer bulk in wafer-spun, plasma-treated polydimethylsiloxane. HT Evensen, H Jiang, KW Gotrik, F Denes, RW Carpick. Nano letters 9 (8), 2884-2890

Polydiacetylene films: a review of recent investigations into chromogenic transitions and nanomechanical properties. RW Carpick, DY Sasaki, MS Marcus, MA Eriksson, AR Burns. Journal of Physics: condensed matter 16 (23), R679

Research Description:

The Cheng lab focuses on the fundamental studies of nanomaterial-cell interactions and the development of new biomaterials for cancer immunotherapy and antigen-specific immune tolerance.

Keywords:

Protein adsorption, long circulation, tumor penetration, drug delivery, immunoengineering

Research Description:

Design of drug, gene, protein and cell delivery systems: Magnetically targeted therapy of arterial restenosis. Nanocarrier-based site-specific gene delivery methods. Prodrug and codrug design. Nanocarrier/prodrug combinations for treating solid tumors

Research Description:

autoimmunity/inflammation/thrombosis and other immunohematologic disorders

Research Description:

pulmonary delivery, formulation, nanoparticle, preclinical models, liposomes, imaging

Keywords:

pulmonary delivery, formulation, nanoparticle, preclinical models, liposomes, imaging

Comments:

David is currently the VP of Research at Insmed, Inc, where he is part of a team developing novel, targeted therapies to help serve the critical unmet needs of patients battling serious rare diseases. Prior to joining Insmed in 2018, David worked at Aradigm (1996 to 2018) covering all phases of product development and led the development of preclinical research, CMC activities and intellectual property. Prior to joining Aradigm, David worked at Genentech, Inc. (1988 to 1996) developing and characterizing the delivery of protein aerosols to the airways, culminating with the approval of Pulmozyme® rhDNase for the management of cystic fibrosis in 1993. David holds a chemical engineering degree from MIT (SB) and UC Davis (MS) and a pharmacy degree from the University of Sydney (PhD).

Research Description:

Nanoparticle drug delivery, interactions between nanoparticle and biomaterial surfaces, functionalization of nanoparticles, nanoparticle kinetics.

Keywords:

polymer, nanoparticles, biofilm

Recent Publications:

“Single-particle tracking of nonsticky and sticky nanoparticles in polymer melts.” Jinseok Park, E. J. Bailey, R. J. Composto, K. I. Winey*, Macromolecules, published online 2020.

“Nanoparticle diffusion during gelation of tetra poly(ethylene glycol) provides insight into nanoscale structural evolution” E. Parrish, K. A. Rose, M. Cargnello, C. B. Murray, D. Lee, R. J. Composto*, Soft Matter, 16, 2256-2265, 2020.

“Particle tracking of nanoparticles in soft matter,” K. A. Rose, M. Molaei, MJ, Boyle, D Lee*, JC, Crocker* and RJ Composto*, Journal of Applied Physics, doi: 10.1063/5.0003322

“Polymer blend systems with an added solvent,” S.M. Maguire, H-J, Chung and Russell J. Composto*, Chapter 4. Soft Matter Series # 10, Bijels: Bicontinuous Particle-stabilized Emulsions, P.S. Clegg, Royal Society of Chemistry, 2020.

“Nanorod position and orientation in vertical cylinder block copolymer films”

B.Rasin, BJ Lindsay, X Ye, JS Meth, CB Murray, RA Riggleman, RJ Composto

Soft Matter 16 (12) 3005-3014.

Kinetic Monitoring of Block Copolymer Self-Assembly Using In Situ Spectroscopic Ellipsometry

CR Bilchak, S Govind, G Contreas, B Rasin, SM Maguire, RJ Composto, ...

ACS Macro Letters 9 (8), 1095-1101

pH-Mediated nanoparticle dynamics in hydrogel nanocomposites, KA Rose, D Lee and RJ Composto, Soft Matter, DOI:10.1039/d0sm02213f

“Interfacial Compatibilization in Ternary Polymer Nanocomposites: Comparing Theory and Experiments S. M. Maguire, N. Krook, A. Kulshreshtha, C. Bilchak, R. Brosnan, A. Pana, P. Rannou, M. Maréchal, K. Ohno, A. Jayaraman, R. Composto.” Macromolecules 54, 797-811, 2021 DOI: 10.1021/acs.macromol.0c02345.

Research Description:

Dr. Cormode's research focuses on the development of novel and multifunctional nanoparticle contrast agents for medical imaging applications. A current major area is the development of gold and bismuth nanoparticles as contrast agents for computed tomography (CT). The nanoparticles can be further modified to have a variety of additional functional properties, such as fluorescence, MRI contrast or therapeutic effects. Related areas of interest are novel computed tomography-based imaging methods, such as dual energy CT, spectral CT and iterative image reconstruction. These technologies are being applied for structural imaging and molecular imaging of the levels of specific cell types and proteins in vivo. These approaches provide enhanced characterization of cardiovascular diseases and cancers, which should allow improved selection of therapies and monitoring of response to treatments.

An additional area of interest is catalytic nanoparticles for biomedical applications.

Keywords:

Gold nanoparticles, silver nanoparticles, catalytic nanoparticles, computed tomography, contrast agents

Recent Publications:

Nieves, Lenitza M.; Hsu, Jessica, C.; Lau, Kristen C.; Maidment, Andrew D. A.; Cormode, David P.: Silver telluride nanoparticles as biocompatible and enhanced contrast agents for x-ray imaging: an in vivo breast cancer screening study. Nanoscale 13(1): 163-174, January 2021.

Huang, Yue; Liu, Yuan; Shah, Shrey; Kim, Dongyeop; Simon-Soro, Aurea; Ito, Tatsuro; Hajfathalian, Maryam; Li, Yong; Alawi, Faizon; Cormode, David P.; Koo, Hyun. : Bacterial pathogen targeting via bi-functional hybrid nanozyme triggered by biofilm microenvironment. Biomaterials 268: 120581, January 2021.

Naha, Pratap C.; Hsu, Jessica C.; Kim, Johoon; Shah, Shrey; Bouché, Mathilde; Si-Mohamed, Salim; Rosario-Berrios, Derick N.; Douek, Philippe; Hajfathalian, Maryam; Yasini, Parisa; Singh, Sanjay; Rosen, Mark A.; Morgan, Matthew A.; Cormode, David P. .: Dextran Coated Cerium Oxide Nanoparticles: A Computed Tomography Contrast Agent for Imaging the Gastrointestinal Tract and Inflammatory Bowel Disease. ACS Nano 14(8): 10187–10197, August 2020.

Hsu, Jessica; Nieves, Lenitza M.; Betzer, Oshra; Sadan, Tamar; Noël, Peter B.; Popovtzer, Rachela; Cormode, David P.: Nanoparticle contrast agents for X-ray imaging applications. WIREs Nanomedicine & Nanobiotechnology 12(6): e1642, May 2020 Notes: Highlighted in Advanced Science News: https://www.advancedsciencenews.com/combining-nanoparticles-with-new-x-ray-technologies-could-revolutionize-imaging-diagnosis/

Kim, Johoon; Silva, Alex B.; Hsu, Jessica C.; Maidment, Portia S. N.; Shapira, Nadav; Noël, Peter B.; Cormode, David P.: Radioprotective garment inspired biodegradable polymetal nanoparticles for enhanced CT contrast production. Chemistry of Materials 32(1): 381-391, January 2020.

Hsu, Jessica, C.; Cruz, Emma D.;Lau, Kristen C.; Bouché, Mathilde; Maidment, Andrew D. A.; Cormode, David P. : Renally-excretable and size-tunable silver sulfide nanoparticles for dual energy mammography or computed tomography. Chemistry of Materials 31(19): 7845-7854, October 2019.

Dong, Yuxi C.; Hajfathalian, Maryam; Maidment, Portia S. N.; Hsu, Jessica C.; Naha, Pratap C.; Si-Mohamed, Salim; Breuilly, Marine; Kim, Johoon; Chhour, Peter; Douek, Philippe; Litt, Harold I.; Cormode, David P.: Effect of gold nanoparticle size on their properties as contrast agents for computed tomography. Scientific Reports September 2019.

Bouché, Mathilde; Pühringer, Manuel; Iturmendi, Aitziber; Amirshaghaghi, Ahmad; Tsourkas, Andrew; Teasdale, Ian; Cormode, David P.: Activatable hybrid polyphosphazene-AuNP nanoprobe for ROS detection by bimodal PA/CT imaging. ACS Applied Materials and Interfaces 11(32): 28648-28656, August 2019.

Naha, Pratap C.; Liu, Yuan; Hwang, Geelsu; Huang, Yue; Gubara, Sarah; Jonnakuti, Venkata; Simon-Soro, Aurea; Kim, Dongyeop; Gao, Lizeng; Koo, Hyun.; Cormode, David P.: Dextran coated iron oxide nanoparticles as biomimetic catalysts for localized and pH-activated biofilm disruption. ACS Nano 13(5): 4960-4971, May 2019 Notes: Topic of a perspective article ‘Benoit, Danielle S. W.; Sims Jr., Kenneth R.; Fraser, David Nanoparticles for Oral Biofilm Treatments. ACS Nano, 2019, 13, 5, 4869-4875’

Hajfathalian, Maryam; Amirshaghaghi, Ahmad; Naha, Pratap C.; Chhour, Peter; Hsu, Jessica, C.; Douglas, Keely; Dong, Yuxi; Sehgal, Chandra M.; Tsourkas, Andrew; Neretina, Svetlana; Cormode, David P. : Wulff in a cage gold nanoparticles as contrast agents for computed tomography and photoacoustic imaging. Nanoscale 10: 18749 – 18757, October 2018.

Research Description:

Microencapsulation of enzymes

Research Description:

My research expertise is on fabrication of nanocomposite-based scaffolds for neural tissue engineering applications whereas my current research focus is on developing functional nanofiber-based scaffolds for cardiac and skeletal muscle regeneration.

In this context, my research aligns with a couple of themes in the center: a) Targeted Biological Agents (Biologics) and b) Polymeric and Synthetic Nano-platforms.

Keywords:

nanofiber, electrospinning, nerve regeneration, nanoparticles, muscle repair.

Recent Publications:

J.C Burrell, S. Das, F.A. Laimo, K.S. Katiyar, K.D. Browne, R.B. Shultz, V.J. Tien, P.T. Vu, D. Petrov, Z.S. Ali, J. M. Rosen, D.K. Cullen: Engineered neuronal microtissue provides exogenous axons for delayed nerve fusion and rapid neuromuscular recovery in rats. Bioactive Materials, 18 (2022), 339-353. https://doi.org/10.1016/j.bioactmat.2022.03.01.

S. Das, K.D. Browne, F.A. Laimo, J.C. Maggiore, M.C. Hilman, H. Kaisaier, C.A. Aguilar, Z.S. Ali, F. Mourkioti, D.K. Cullen: Preinnervated tissue-engineered muscle promotes a pro-regenerative microenvironment following volumetric muscle loss. Communications Biology, 3 (2020) 330. https://doi.org/10.1038/s42003-020-1056-4.

S. Das, W.J. Gordián-Vélez (cfa), H.C. Ledebur, F. Mourkioti, P. Rompolas, H.I. Chen, M.D. Serruya, D.K. Cullen: Innervation: the missing link for biofabricated tissues and organs. NPJ Regen Med. 5 (2020) 11. https://doi.org/10.1038/s41536-020-0096-1.

K.S. Katiyar, L.A. Struzyna, S. Das, D.K. Cullen: Stretch growth of motor axons in custom mechanobioreactors to generate longprojecting axonal constructs. J. Tissue Eng. Regen. Med. 13 (2019) 2040–2054. https://doi.org/10.1002/term.2955.

K.S. Katiyar, S. Das, J.C. Burrell, D.K. Cullen: Scaffolds for bridging sciatic nerve gaps, in: M. Mozafari, F. Sefat, A. Atala (Eds.), Handbook of Tissue Engineering Scaffolds: Volume Two, Woodhead Publishing, 2019: pp. 67–93. https://doi.org/10.1016/B978-0-08-102561-1.00003-8.

D.O. Adewole, S. Das, D. Petrov, D.K. Cullen: Scaffolds for brain tissue reconstruction, in: M. Mozafari, F. Sefat, A. Atala (Eds.), Handbook of Tissue Engineering Scaffolds: Volume Two, Woodhead Publishing, 2019: pp. 3–29. https://doi.org/10.1016/B978-0-08-102561-1.00001-4.

W. Shen, S. Das, F. Vitale, A. Richardson, A. Ananthakrishnan, L.A. Struzyna, D.P. Brown, N. Song, M. Ramkumar, T. Lucas, D.K. Cullen, B. Litt, M.G. Allen: Microfabricated intracortical extracellular matrix-microelectrodes for improving neural interfaces. Microsyst Nanoeng. 4 (2018) 30. https://doi.org/10.1038/s41378-018-0030-5.

S. Das, M. Sharma, D. Saharia, K.K. Sarma, E.M. Muir, U. Bora: Electrospun silk-polyaniline conduits for functional nerve regeneration in rat sciatic nerve injury model. Biomed. Mater. 12 (2017) 045025. https://doi.org/10.1088/1748-605X/aa7802.

S. Das, A. Carnicer-Lombarte, J.W. Fawcett, U. Bora: Bio-inspired nano tools for neuroscience. Prog. Neurobiol. 142 (2016) 1–22. https://doi.org/10.1016/j.pneurobio.2016.04.008.

S. Das, M. Sharma, D. Saharia, K.K. Sarma, M.G. Sarma, B.B. Borthakur, U. Bora: In vivo studies of silk based gold nano-composite conduits for functional peripheral nerve regeneration. Biomaterials, 62 (2015) 66–75.

Research Description:

The Day Lab's mission is to transform the study, detection, and treatment of cancer and other diseases with engineered nanomaterials

Keywords:

Nanomedicine, photothermal therapy, gene regulation, signal cascade interference, biomimicry, translational research

Recent Publications:

1. Dang MN, Gomez Casas C, Day ES. Photoresponsive miR-34a/nanoshell conjugates enable light-triggered gene regulation to impair the function of triple-negative breast cancer cells. Nano Letters. 2020; doi: 10.1021/acs.nanolett.0c03152.

2. Valcourt DM, Day ES. Dual regulation of miR-34a and Notch signaling in triple-negative breast cancer by antibody/miRNA nanocarriers. Molecular Therapy-Nucleic Acids. 2020; 21: 290-298

3. Valcourt DM, Dang MN, Scully MA, Day ES. Nanoparticle-mediated co-delivery of Notch-1 antibodies and ABT-737 as a potent treatment strategy for triple-negative breast cancer. ACS Nano. 2020; 14(3): 3378-3388.

4. Wang J, Dang MN, Day ES. Inhibition of Wnt signaling by Frizzled7 antibody-coated nanoshells sensitizes triple-negative breast cancer cells to the autophagy regulator chloroquine. Nano Research. 2020; 13: 1693–1703.

5. Wang J*, Potocny AM*, Rosenthal J#, Day ES#. Gold nanoshell-linear tetrapyrrole conjugates for near infrared-activated dual photodynamic and photothermal therapies. ACS Omega. 2020; 5(1): 926-940.*equal contribution #co-corresponding authors

6. Kapadia CH, Ioele SA, Day ES. Layer-by-layer assembled PLGA nanoparticles carrying miR-34a cargo inhibit the proliferation and cell cycle progression of triple-negative breast cancer cells. Journal of Biomedical Materials Research Part A. 2019; doi: 10.1002/jbm.a.36840.

7. Melamed JR, Ioele SA, Hannum AJ, Ullman VM, Day ES. Polyethylenimine-spherical nucleic acid nanoparticles against Gli1 reduce the chemoresistance and stemness of glioblastoma cells. Molecular Pharmaceutics. 2018; 15(11): 5135-5145.

8. Melamed JR, Kreuzberger NL, Goyal R, Day ES. Spherical nucleic acid architecture can improve the efficacy of polycation-mediated siRNA delivery. Molecular Therapy-Nucleic Acids. 2018; 12: 207-219.

9. Riley RS, Dang MN, Billingsley MM, Abraham B, Gundlach L, Day ES. Evaluating the mechanisms of light-triggered siRNA release from nanoshells for temporal control over gene regulation. Nano Letters. 2018; 18(6): 3565-3570.

10. Riley RS, Day ES. Frizzled 7 antibody-functionalized nanoshells enable multivalent binding for Wnt signaling inhibition in triple negative breast cancer cells. Small. 2017; 13(26): 1700544.

Recent Publications:

https://scholar.google.com/citations?user=Wyggy_QAAAAJ&hl=en

Research Description:

Polymersomes and filomicelles were invented and first applied to drug delivery in the Discher lab. These block copolymer based assemblies, like many (all) nanoparticles, can improve efficacy/safety but they are also taken up by phagocytic cells, especially when compared to 'self' cells such as platelets and red cells. As we realized these limitations, an immunology group elsewhere had proposed a ubiquitous protein, CD47, signals against phagocytic uptake. We followed up and were the first to show inhibition at a 'phagocytic synapse' when CD47 is displayed on nanoparticles, viruses, and other surfaces. We now use this pathway to make macrophages eat cancer.

Research Description:

Nanoparticle drug delivery

Keywords:

single cell, transcriptomics, genomics, neurobiology, RNA biology, RNA translation, subcellular organelles

Research Description:

Animals models of brain disorders in which to test promising targeted therapeutics

Keywords:

Neurobiology of motivated behavior, depression, stress, addiction, sepsis, brain-bladder communication, hippocampus, dentate gyrus, neurogenesis, stem cells

Recent Publications:

1) Zanni G, DeSalle MJ, Deutsch HM, Barr GA^ Eisch AJ^. Female and male rats readily consume and prefer oxycodone to water in a chronic, continuous access, two-bottle oral voluntary paradigm. Neuropharmacology. 167:107978. doi: 10.1016/j.neuropharm.2020.107978 (2020). PMID 32001238.

^co-senior and co-corresponding authors

2) Ortega SB*, Torres VO*, Latchney SE, Whoolery CW, Noorbhai IZ, Poinsatte K, Selvaraj UM, Benson MA, Meeuwissen AJM, Plautz EJ, Kong X, Ramirez DM, Ajay AD, Meeks JP, Goldberg MP, Monson NL, Eisch AJ, Stowe AM. B cells migrate into remote brain areas and support neurogenesis and functional recovery after focal stroke in mice. Proceedings of the National Academy of Sciences USA. Feb 12:201913292. doi: 10.1073/pnas.1913292117. Epub ahead of print. (2020) PMID 32051245, PMC 7060723.

*equal contribution

3) Tran FH*, Spears SL*, Ahn KJ, Eisch AJ, Yun S. Does chronic systemic injection of the DREADD agonists clozapine-N-oxide or compound 21 change behavior relevant to locomotion, exploration, anxiety, and depression in male non-DREADD-expressing mice? Nov (2020). 739:135432. Neuroscience Letters. doi: 10.1016/j.neulet.2020.135432. PMID 33080350.

*equal contribution

4) Clark LR, Yun S, Acquah NK, Kumar PL, Metheny HE, Paixao RCC, Cohen AS, Eisch AJ. Mild traumatic brain injury induces transient, sequential increases in proliferation, neurogenesis, and cell survival: a time course study in the male mouse dentate gyrus. (2021) Frontiers in Neuroscience. Part of special issue “New Insights into Adult Neurogenesis and Neurodegeneration: Challenges for Brain Repair”. 07 January. doi: org/10.1101/2020.10.07.330118. PMID 33488351, PMC 7817782

5) Zanni G*, Robinson-Drummer PA*, Dougher AA, Deutsch HM, DeSalle MJ, Teplitsky D, Vemulapalli A, Sullivan RM, Eisch AJ^, Barr GA^. Maternal Continuous Oral Oxycodone Self-Administration Alters Pup Affective/Social Communication but not Spatial Learning or Sensory-Motor Function. (2021) Drug Addiction and Dependence. Apr 1;221:108628. doi: 10.1016/j.drugalcdep.2021.108628. Epub 2021 Feb 17. PMID 33761428.

*equal contribution

^co-corresponding and senior authors

6) Soler I^, Yun S^*, Reynolds RP^^, Whoolery CW^^, Tran FH, Kumar PL, Rong Y, DeSalle MJ, Gibson AD, Stowe AM, Kiffer FC, Eisch AJ*. Multi-Domain Touchscreen-Based Cognitive Assessment of C57BL/6J Female Mice Shows Whole-Body Exposure to 56Fe Particle Space Radiation in Maturity Improves Discrimination Learning Yet Impairs Stimulus-Response Rule-Based Habit Learning. (2021) Frontiers in Behavioral Neuroscience. Oct; 15:1-25. doi: 10.3389/fnbeh.2021.722780. PMID 34707486, PMC 8543003.

^equal contribution co-first authors

^^equal contribution co-second authors

*co-corresponding author

7) Kiffer FC, Luitel K, Tran FH, Patel RA, Guzman CS, Soler I, Xiao R, Shay JW, Yun S, Eisch AJ. Effects of a 33-ion sequential beam galactic cosmic ray analog on male mouse behavior and evaluation of CDDO-EA as a radiation countermeasure. (2022) Behavioural Brain Research Feb 15;419:113677. doi: 10.1016/j.bbr.2021.113677. Epub 2021 Nov 21. PMID 34818568 PMCID 9755463.

8) Antila A, Kwak I, Choi A, Pisiotti A, Covarrubias I, Baik J, Eisch AJ, Beier KT, Thomas SA, Weber F, Chung S. A noradrenergic-hypothalamic neural substrate for stress-induced sleep disturbances. (2022) Proceedings of the National Academy of Sciences, USA. Nov 8;119(45):e2123528119. doi: 10.1073/pnas.2123528119. Epub 2022 Nov 4. PMID 36331996, PMCID 9659376.

9) Guez Barber D*, Colón LM*, Raphael D, Wragan MA, Yun S, Eisch AJ. Microglia cell number, density, and morphology classification at postnatal day 10 in dentate gyrus of female and male C57BL/6J mice. (2023) Neuroscience Letters. Apr 23;803:137171. doi: 10.1016/j.neulet.2023.137171. Epub 2023 Mar 8. PMID 36898652. PMC in progress.

*equal contribution

10) Yun S, Soler I, Fionya T, Haas HA, Shi R, Bancroft GL, Suarez M, de Santis CR, Reynolds RP, Eisch AJ. Behavioral pattern separation and cognitive flexibility are enhanced in a mouse model of increased lateral entorhinal cortex-dentate gyrus circuit activity. Frontiers in Behavioral Neuroscience. (2023) Jun 1;17:1151877. doi: 10.3389/fnbeh.2023.1151877. eCollection 2023. PMID 37324519. PMC in progress.

Keywords:

Nanoparticles, drug delivery, biomaterials

Research Description:

Immunotherapy, glioma treatment, angiogenesis

Keywords:

angiogenesis, immunotherapy, glioma stem cells

Recent Publications:

Huang M, T Liu, Ma P, Mitteer RA, Zhang Z, Kim HJ, Yeo E, Zhang D, Cai P, Li C, Zhang L, Zhao B, Roccograndi L, O’Rourke DM, Dahmane N, Gong Y, Koumenis C, Fan Y.: c-Met-mediated endothelial plasticity drives aberrant vascularization and chemoresistance in glioblastoma. J Clin Invest. 126(5): 1801-14, May 2016.

Zhang Y, He Q, Hu Z, Feng Y, Fan L, Tang Z, Yuan J, Shan W, Li C, Hu X, Tanyi JL, Fan Y, Huang Q, Montone K, Dang CV, Zhang L.: Long noncoding RNA LINP1 regulates repair of DNA double-strand breaks in triple-negative breast cancer. Nat Struct Mol Biol 23(6): 522-30. April 2016.

Yan X, Hu Z, Feng Y, Hu X, Yuan J, Zhao SD, Zhang Y, Yang L, Shan W, He Q, Fan L, Kandalaft LE, Tanyi JL, Li C, Yuan CX, Zhang D, Yuan H, Hua K, Lu Y, Katsaros D, Huang Q, Montone K, Fan Y, Coukos G, Boyd J, Sood AK, Rebbeck T, Mills GB, Dang CV, Zhang L. : Comprehensive Genomic Characterization of Long Non-coding RNAs across Human Cancers. Cancer Cell 28(4): 529-40, October 2015.

Mitteer RA, Wang YL, Shah J, Gordon S, Fager M, Guardiola-Salmeron C, Carabe-Fernandez A*, and Fan Y* : Proton beam radiation induces DNA damage and cell apoptosis in glioma stem cells through reactive oxygen species. Sci Rep 5: 13961, September 2015 Notes: *co-corresponding author.

Research Description:

In-silico Systems Biomedicine, Physical Biology

Keywords:

Targeted Drug delivery, Engineered nanomaterials, chronic infection, biofilm

Recent Publications:

https://www.ncbi.nlm.nih.gov/myncbi/1NIUjh9mgkcA9n/bibliography/public/

Comments:

Dr. Samaneh Farokhirad is an Assistant Professor in the Department of Mechanical and Industrial Engineering at New Jersey Institute of Technology (NJIT). Prior to joining NJIT, she was a Postdoctoral Research Associate in the Department of Chemical and Biomolecular Engineering and Penn Institute for computational science at University of Pennsylvania and a Postdoctoral Research Fellow in the Computational Multiphase Flow Dynamics Group at City College of New York (CCNY). She received her Ph.D. and M.Phil. degrees in Mechanical Engineering from CCNY, and B.S. degree in Mechanical Engineering from Sharif University of Technology

The central aim of her research program is the development of multiscale modeling and novel simulation methods to study the mechanics and physics of soft matter, biological flows, and transport of particles and cells. Additionally, she explores interfacial transport processes in heterogeneous materials, which have applications in many fields ranging from targeted drug delivery to petroleum exploration.

Research Description:

Lung cancer translational research

Keywords:

Mouse models, lung cancer

Recent Publications:

Walter DM, Yates TJ, Ruiz-Torres M, Kim-Kiselak C, Gudiel AA, Deshpande C, Wang WZ, Cicchini M, Stokes KL, Tobias JW, Buza E, Feldser DM. RB constrains lineage fidelity and multiple stages of tumour progression and metastasis. Nature. 2019 May;569(7756):423-427. doi: 10.1038/s41586-019-1172-9. Epub 2019 May 1. PMID: 31043741

Stokes, K, Acosta, J, Lauderback, B, Robles-Oteiza, C, Cicchini, M and Feldser, D.M. Natural killer cells limit the clearance of senescent lung adenocarcinoma cells. Oncogenesis. 2019 Apr 1;8(4):24. doi:10.1038/s41389-019-0133-3. PMID: 30936429

Acosta J, Wang W, and Feldser DM (2018). Off and Back-On Again: A Tumor Suppressor’s Tale. Oncogene. 2018 Mar 15. doi: 10.1038/s41388-018-0186-3. [Epub ahead of print] Review. PMID: 29540833

Walter DM, Venancio OS, Buza EL, Tobias JW, Deshpande C, Gudiel AA, Kim-Kiselak C, Cicchini M, Yates TJ, and Feldser DM (2017). Systematic in vivo inactivation of chromatin regulating enzymes identifies Setd2 as a potent tumor suppressor in lung adenocarcinoma. Cancer Research. 2017 Feb 15. pii: canres.2159.2016. doi: 10.1158/0008-5472.CAN-16-2159. [Epub ahead of print]. PMID: 28202515

Cicchini M, Buza E.L., Sagal K.M., Gudiel A.A., Durham A.C., and Feldser DM (2017). Context dependent effects of amplified MAPK signaling during lung adenocarcinoma initiation and progression. Cell Reports. 2017 Cell Reports 2017 Feb 21;18(8):1958-1969. PMID: 28228261

Robles-Oteiza C, Taylor SE, Yates T, Cicchini M, Lauderback B, Cashman C, Burds AA, Winslow M, Jacks T, Feldser DM (2015). XTR: A recombinase-based system for regulating gene function in a conditional and reversible manner. Nat Commun. 2015 Nov 5;6:8783. PMID: 26537451

Keywords:

Cardiovascular Medicine, Aortic Valve Disease, Mitral Valve Disease, Aortic Aneurysm, Angiogenesis, Tissue Engineering, Biomaterials, Cell Biology, Molecular Biology

Research Description:

gene therapy, atherosclerosis, restenosis

Research Description:

Personalized therapeutics for pediatric sepsis

Keywords:

Pediatric

Sepsis

Acute kidney injury

Research Description:

Targeted drug delivery, computational modeling, protein therapeutics

Keywords:

Pharmacokinetics, Protein engineering, Drug delivery

Research Description:

Immunology, Cancer immunotherapy,, diabetics, imaging spectrometry,

Research Description:

Controlled Drug Delivery System

Synthetic materials to direct cell fate

Keywords:

drug delivery, polymers, synthetic materials, stem cells

Research Description:

Microcirculation, endothelial injury, circulatory shock

Recent Publications:

Greenwood JC, Jang DH, Spelde AE, et al. Low microcirculatory perfused vessel density and high heterogeneity are associated with increased intensity and duration of lactic acidosis after cardiac surgery with cardiopulmonary bypass. Shock. 2021;56(2):245-254.

Greenwood JC, Jang DH, Hallisey SD, et al. Severe impairment of microcirculatory perfused vessel density is associated with postoperative lactate and acute organ injury after cardiac surgery. J Cardiothorac Vasc Anesth. 2021;35(1):106-115.

Keywords:

Microfluidics, drug delivery systems

Keywords:

Drug delivery, gene therapy, biomaterials, nanotechnology

Research Description:

Fluorescence, Glioma, amino acid transporters, small molecules, liposomes

Keywords:

near-infrared fluorescence, targeted dyes, low grade glioma, image-guidance

Recent Publications:

Rogalla S, Flisikowski K, Gorpas D, Mayer AT, Flisikowska T, Mandella MJ, Ma X, Casey KM, Felt SA, Saur D, Ntziachristos V, Schnieke A, Contag CH, Gambhir SS, Harmsen S.: Biodegradable fluorescent nanoparticles for early endoscopic detection of colorectal carcinogenesis. Advanced Functional Materials Oct 2019 Notes: DOI: 10.1002/adfm.201904992

Harmsen S, Rogalla S, Huang R, Spaliviero M, Neuschmelting V, Hayakawa Y, Lee Y, Tailor Y, Toledo-Crow R, Kang JW, Samii JM, Karabeber H, Davis RM, White JR, van de Rijn M, Gambhir SS, Contag CH, Wang TC, Kircher MF.: Detection of Premalignant Gastrointestinal Lesions Using Surface-Enhanced Resonance Raman Scattering-Nanoparticle Endoscopy. ACS Nano. 13(2): 1354-1364, Feb 2019.

Neuschmelting V*, Harmsen S*, Beziere N, Lockau H, Hsu HT, Huang R, Razansky D, Ntziachristos V, Kircher MF.: Dual-modality surface-enhanced resonance Raman scattering (SERRS)- and multispectral optoacoustic tomography nanoparticle approach for brain tumor delineation. Small 14(23), May 2018 Notes: doi: 10.1002/smll.201800740.

Jurgieleiwcz P, Harmsen S, Wei E, Bachmann M.H., Ting R, Aras O.: New imaging probes to track cell fate: reporter genes in stem cell research. Cellular and Molecular Life Sciences 74(24): 4455-69, Dec 2017.

Keywords:

Medicinal chemistry, drug delivery, prodrug design, and pharmaceutics.

Research Description:

Ligand-targeted delivery of macromolecular therapeutics against intracellular targets, including oligonucleotides, peptides and proteins. Conjugates and nanoparticle formulations for enhancing uptake and endosomal release of membrane-impermeable drugs.

Keywords:

Targeted delivery, endosomal escape, oligonucleotide therapeutics, drug conjugates, LNP

Keywords:

immunoengineering, cardiac pathologies, cytokine traps

Research Description:

Design and synthesis of dendritic macromolecules and nanoparticle dendrimer hybrids suitable for targeted drug delivery and imaging.

Keywords:

Nanochemistry, Nanoparticles, Dendrimers, Hybrid materials, Organic Synthesis

Recent Publications:

1. Zhao, T.; Oh, N.; Jishkariani, D.; Zhang, M.; Wang, H.; Li, N.; Lee, J. D.; Zeng, C.; Muduli, M.; Choi, H-J.; Su, D.; Murray. C. B.; Kagan, C. R. General Synthetic Route to High-Quality Colloidal III–V Semiconductor Quantum Dots Based on Pnictogen Chlorides, J. Am. Chem. Soc. 2019, 141, 15145.

2. Jishkariani, D.; Elbert, K. C.; Wu, Y.; Lee. J. D.; Hermes, M.; Wang, D.; Blaaderen, A. V.; Murray, C. B. Nanocrystal Core Size and Shape Substitutional Doping and Underlying Crystalline Order in Nanocrystal Superlattices ACS Nano, 2019, 13, 5712.

3. Lee. J. D.; Jishkariani, D.; Yingrui, z.; Najmr. S.; Rosen, D.; Kikkawa, J.; Stach, E. Murray, C. B. Tuning the Electrocatalytic Oxygen Reduction Reaction Activity of PtCo Nanocrystals by Cobalt Concentration with Atomic-Scale Understanding, ACS Applied Materials & Interfaces, 2019, 11, 26789.

4. Jishkariani, D.; MacDermaid, C. M.; Timsina, Y. N.; Grama, S.; Gillani, S. S.; Divar, M.; Yadavali, S. S.; Moussodia, R-O.; Leonawarat, P.; Berrios Camacho, A. M.; Walter, R.; Goulian, M.; Klein, M. L.; Percec, V. Self-interrupted Synthesis of Sterically Hindered Aliphatic Polyamide Dendrimers Proc. Nat. Acad. Sci. 2017, 114, E2275.

5. Jishkariani, D.; Wu, Y.; Wang, D.; Liu, Y.; Blaaderen, A. V.; Murray, C. B. Preparation and Self-Assembly of Dendronized Janus Heterodimers ACS Nano, 2017, 11, 7958.

6. Jishkariani, D.; Lee, J. D.; Yun, H.; Paik, T.; Kikkawa, J. M.; Kagan, C. R.; Donnio, B.; Murray, C. B. Dendritic effect and Magnetic Permeability in Dendronized Magnetic Nanoparticles Nanoscale, 2017, 9, 13922-13928.

7. Diroll, B. T.; Jishkariani, D.; Cargnello, M.; Murray, C. B.; Donnio, B. Polycatenar Ligand Control of the Synthesis and Self-Assembly of Colloidal Nanocrystals J. Am. Chem. Soc. 2016, 10508.

8. Malassis, L.; Jishkariani, D.; Murray, C. B.; Donnio, B. Dendronization-induced phase-transfer, stabilization and self-assembly of large colloidal Au nanoparticles Nanoscale, 2016, 8, 13192.

9. Jishkariani, D.; Diroll, B. T.; Cargnello, M.; Klein, D. R.; Hough, L. A.; Murray, C. B.; Donnio, B. Dendron-Mediated Engineering of Interparticle Separation and Self-Assembly in Dendronized Gold Nanoparticles Superlattices. J. Am. Chem. Soc. 2015, 137, 10728.

10. Diroll, B. T.; Weigandt K. M.; Jishkariani, D.; Cargnello, M.; Murphy R. J.; Hough, L. A.; Murray, C. B.; Donnio, B. Quantifying “Softness” of Organic Coatings on Gold Nanoparticles using Correlated Small-Angle X-Ray and Neutron Scattering. Nano Lett, 2015, 15, 8008.

Research Description:

Drug Delivery, Immunology

Research Description:

Thermal properties of nanoparticles, heat transfer between nanoparticles and surrounding media, nanoparticle heating mechanisms

Research Description:

II am interested in using high-density lipoprotein (HDL)-inspired nanodevices to increase cholesterol efflux from macrophages and to manipulate plasma lipid levels. In one project I collaborated with a medical nanotechnology group at the Northwestern University to produce and test a gold-based mimic of HDL. Presently, I collaborate with Dr. Yinghui Zhong from the Drexel University on dextran sulfate/chitosan-based nanoparticles for removing triglyceride (TG)-rich lipoprotein from plasma. TG is an independent risk factor in cardiovascular disease. Dextran sulfate nanoparticles can bind apolipoprotein B in TG-rich lipoprotein and promote TG-lipoprotein removal by the Kupffer cells of the liver. Recently, I also become interested in protein and DNA deliver to the brain.

Keywords:

gold nanoparticles, dextran sulfate/chitosan-based nanoparticles

Recent Publications:

Robust passive and active efflux of cellular cholesterol to a designer functional mimic of high density lipoprotein. Luthi AJ, Lyssenko NN, Quach D, McMahon KM, Millar JS, Vickers KC, Rader DJ, Phillips MC, Mirkin CA, Thaxton CS.

Keywords:

Immune engineering, vaccines, protein engineering, cell therapy

Recent Publications:

1. E Dane, A Belessiotis-Richards, C Backlund, J Wang, K Hidaka, L Milling, S Bhagchandani, M Melo, NA Li, N Donahue, K Ni, L Ma, M Okaniwa, M Stevens, A Alexander-Katz, D. J. Irvine. Delivery of STING agonists using tumor-penetrating PEGylated lipid nanodiscs primes sustained anti-cancer immunity. Nat Materials, accepted, (2022)

2. L. Ma, T. Dichwalkar, J. Y. H. Chang, B. Cossette, D. Garafola, A. Q. Zhang, M. Fichter, C. Wang, S. Liang, M. Silva, S. Kumari, N. K. Mehta, W. Abraham, N. Thai, N. Li, K. D. Wittrup, D. J. Irvine: Enhanced CAR–T cell activity against solid tumors by vaccine boosting through the chimeric receptor, Science 365, 162–168 (2019).

3. N. Momin, N. K. Mehta *, N. R. Bennett *, L. Ma *, J. R. Palmeri, M. M. Chinn, E. A. Lutz, B. Kang, D. J. Irvine, S. Spranger, K. D. Wittrup: Anchoring of intratumorally administered cytokines to collagen safely potentiates systemic cancer immunotherapy, Sci Transl Med 11, eaaw2614 (2019). [* Equal contribution]

Research Description:

Nanoparticle imaging agents.

Research Description:

Our research team develops nanotechnology tools to better understand cardiometabolic diseases such as atherosclerosis, type 2 diabetes, and obesity. We engineer, make, and test new imaging probes, drug delivery vehicles, and sensors that help diagnose and treat these conditions. In addition to imaging and drug delivery projects, our laboratory investigates lipoproteins and their function and metabolic biology of immune cells. We also have a long-standing interest in toxicology of synthetic and environmental nano-/microparticles and their effects on cardiometabolic health.

Cardiovascular drug and gene delivery, immunotherapies for inflammation

Keywords:

MRI, atherosclerosis, thrombosis, HFpEF

Recent Publications:

- Nanotheranostics. 2019 Nov 1;3(4):342-355; PMID: 31723548

- Sci Rep. 2016 Feb 11;6:20646; PMID: 26865459

- J Control Release. 2015 Nov 10;217:243-55; PMID: 26386437

Research Description:

Drug targeting, red cells, endothelial targeting, drug delivery, neurovascular inflammation, brain injury, brain delivery, gene therapy, thrombosis and hemostasis, vascular biology, molecular imaging...

Recent Publications:

1. Red blood cell-hitchhiking boosts delivery of nanocarriers to chosen organs by orders of magnitude. Brenner JS, Pan DC, Myerson JW, Marcos-Contreras OA, Villa CH, Patel P, Hekierski H, Chatterjee S, Tao JQ, Parhiz H, Bhamidipati K, Uhler TG, Hood ED, Kiseleva RY, Shuvaev VS, Shuvaeva T, Khoshnejad M, Johnston I, Gregory JV, Lahann J, Wang T, Cantu E, Armstead WM, Mitragotri S, Muzykantov V. Nat Commun. 2018 Jul 11;9(1):2684. doi: 10.1038/s41467-018-05079-7.

2. Flexible Nanoparticles Reach Sterically Obscured Endothelial Targets Inaccessible to Rigid Nanoparticles. Myerson JW, Braender B, Mcpherson O, Glassman PM, Kiseleva RY, Shuvaev VV, Marcos-Contreras O, Grady ME, Lee HS, Greineder CF, Stan RV, Composto RJ, Eckmann DM, Muzykantov VR. Adv Mater. 2018 Aug;30(32):e1802373. doi: 10.1002/adma.201802373. Epub 2018 Jun 28.

3. Molecular engineering of antibodies for site-specific covalent conjugation using CRISPR/Cas9. Khoshnejad M, Brenner JS, Motley W, Parhiz H, Greineder CF, Villa CH, Marcos-Contreras OA, Tsourkas A, Muzykantov VR. Sci Rep. 2018 Jan 29;8(1):1760. doi: 10.1038/s41598-018-19784-2.

4. Vascular endothelial effects of collaborative binding to platelet/endothelial cell adhesion molecule-1 (PECAM-1). Kiseleva RY, Greineder CF, Villa CH, Marcos-Contreras OA, Hood ED, Shuvaev VV, DeLisser HM, Muzykantov VR. Sci Rep. 2018 Jan 24;8(1):1510. doi: 10.1038/s41598-018-20027-7.

5. Hyperfibrinolysis increases blood-brain barrier permeability by a plasmin- and bradykinin-dependent mechanism. Marcos-Contreras OA, Martinez de Lizarrondo S, Bardou I, Orset C, Pruvost M, Anfray A, Frigout Y, Hommet Y, Lebouvier L, Montaner J, Vivien D, Gauberti M. Blood. 2016 Nov 17;128(20):2423-2434. Epub 2016 Aug 16.

6. Sustained correction of FVII deficiency in dogs using AAV-mediated expression of zymogen FVII. Marcos-Contreras OA, Smith SM, Bellinger DA, Raymer RA, Merricks E, Faella A, Pavani G, Zhou S, Nichols TC, High KA, Margaritis P. Blood. 2016 Feb 4;127(5):565-71. doi: 10.1182/blood-2015-09-671420. Epub 2015 Dec 23.

7. The endothelial protein C receptor enhances hemostasis of FVIIa administration in hemophilic mice in vivo. Pavani G, Ivanciu L, Faella A, Marcos-Contreras OA, Margaritis P. Blood. 2014 Aug 14;124(7):1157-65. doi: 10.1182/blood-2014-04-567297. Epub 2014 Jun 23.

8. Ultra-sensitive molecular MRI of vascular cell adhesion molecule-1 reveals a dynamic inflammatory penumbra after strokes. Gauberti M, Montagne A, Marcos-Contreras OA, Le Béhot A, Maubert E, Vivien D. Stroke. 2013 Jul;44(7):1988-96. doi: 10.1161/STROKEAHA.111.000544. Epub 2013 Jun 6.

9. Clot penetration and retention by plasminogen activators promote fibrinolysis. Marcos-Contreras OA, Ganguly K, Yamamoto A, Shlansky-Goldberg R, Cines DB, Muzykantov VR, Murciano JC. Biochem Pharmacol. 2013 Jan 15;85(2):216-22. doi: 10.1016/j.bcp.2012.10.011. Epub 2012 Oct 23.

10. Sustained thromboprophylaxis mediated by an RBC-targeted pro-urokinase zymogen activated at the site of clot formation. Zaitsev S, Spitzer D, Murciano JC, Ding BS, Tliba S, Kowalska MA, Marcos-Contreras OA, Kuo A, Stepanova V, Atkinson JP, Poncz M, Cines DB, Muzykantov VR. Blood. 2010 Jun 24;115(25):5241-8. doi: 10.1182/blood-2010-01-261610. Epub 2010 Apr 21.

Research Description:

Targeted delivery of novel analgesics, mPGES-1 inhibitors, to macrophages

Research Description:

The Mitchell Lab works at the interface of biomaterials science, drug delivery, and cellular and molecular bioengineering to fundamentally understand and therapeutically target biological barriers. The lab applies research findings and the technologies developed to a range of human health applications, including cancer metastasis, immunotherapy, diabetes, cardiovascular disease, and regenerative medicine. Current research projects include: synthesis of novel biomaterials and nanoparticles for the delivery of nucleic acids (siRNA, miRNA, mRNA, CRISPR-Cas9) for cancer therapy; engineering of innate immune cells for immunotherapy and vaccines; investigating the influence of biomaterial chemical structure on in vivo transport to target cells and tissues using high-throughput screening platforms; and novel drug delivery technologies for tissue engineering and regenerative medicine. Mike has received a National Research Service Award from the NIH and a Career Award at the Scientific Interface from the Burroughs Wellcome Fund, recognizing interdisciplinary researchers who are "bridging science fiction with reality."

Keywords:

Drug Delivery, Gene Therapy, Biomaterials, Cellular Engineering, Molecular Engineering, Immunoengineering, Immunotherapy, Oncology, Nanotechnology

Recent Publications:

[1] Guimaraes PPG, Gaglione S, Sewastianik T, Carrasco RD, Langer R, Mitchell MJ. Nanoparticles for Immune Cytokine TRAIL-Based Cancer Therapy. ACS Nano. 2018 Jan 29. doi: 10.1021/acsnano.7b05876;

[2] Mitchell MJ, Webster J, Chung A, Guimarães PP, Khan OF, Langer R. Polymeric mechanical amplifiers of immune cytokine-mediated apoptosis. Nat Commun. 2017 Mar 20;8:14179. doi: 10.1038/ncomms14179;

[3] Oberli MA, Reichmuth AM, Dorkin JR, Mitchell MJ, Fenton OS, Jaklenec A, Anderson DG, Langer R, Blankschtein D. Lipid Nanoparticle Assisted mRNA Delivery for Potent Cancer Immunotherapy. Nano Lett. 2017 Mar 8;17(3):1326-1335. doi: 10.1021/acs.nanolett.6b03329;

[4] Mitchell MJ, Jain RK, Langer R. Engineering and physical sciences in oncology: challenges and opportunities. Nat Rev Cancer. 2017 Nov;17(11):659-675. doi: 10.1038/nrc.2017.83;

[5] Nasajpour A, Mandla S, Shree S, Mostafavi E, Sharifi R, Khalilpour A, Saghazadeh S, Hassan S, Mitchell MJ, Leijten J, Hou X, Moshaverinia A, Annabi N, Adelung R, Mishra YK, Shin SR, Tamayol A, Khademhosseini A. Nanostructured Fibrous Membranes with Rose Spike-Like Architecture. Nano Lett. 2017 Oct 11;17(10):6235-6240;

[6] Wayne EC, Chandrasekaran S, Mitchell MJ, Chan MF, Lee RE, Schaffer CB, King MR. TRAIL-coated leukocytes that prevent the bloodborne metastasis of prostate cancer. J Control Release. 2016 Feb 10;223:215-223. doi: 10.1016/j.jconrel.2015.12.048;

[7] Mitchell MJ, Castellanos CA, King MR. Surfactant functionalization induces robust, differential adhesion of tumor cells and blood cells to charged nanotube-coated biomaterials under flow. Biomaterials. 2015 Jul;56:179-86. doi: 10.1016/j.biomaterials.2015.03.045;

[8] Mitchell MJ, King MR. Leukocytes as carriers for targeted cancer drug delivery. Expert Opin Drug Deliv. 2015 Mar;12(3):375-92. doi: 10.1517/17425247.2015.966684;

[9] Mitchell MJ, Castellanos CA, King MR. Immobilized surfactant-nanotube complexes support selectin-mediated capture of viable circulating tumor cells in the absence of capture antibodies. J Biomed Mater Res A. 2015 Oct;103(10):3407-18. doi: 10.1002/jbm.a.35445;

[10] Mitchell MJ, Wayne E, Rana K, Schaffer CB, King MR. TRAIL-coated leukocytes that kill cancer cells in the circulation. Proc Natl Acad Sci U S A. 2014 Jan 21;111(3):930-5. doi: 10.1073/pnas.1316312111.

Research Description:

Developing acid nanoparticles to restore an low pH to compromised lysosomes in aging diseases. Future interest in the inclusion of lipases and other lysosomal enzymes to enhance clearance of the lipofuscin.

Keywords:

acid nanoparticle, lysosome, neurodegeneration, lipofuscin, autophagy, Alzheimer's disease, Age-related macular degeneration, poly-DL-lactide

Recent Publications:

1. Baltazar, G. C., Guha, S., Boesze-Battaglia, K., Laties, A. M., Tyagi, P., Kompella, U. B., and Mitchell, C. H. (2012) Acidic nanoparticles restore lysosomal pH and degradative function in compromised RPE cells. PloS One 7, e49635.

2. Lee, J. H., McBrayer, M. K., Wolfe, D. M., Haslett, L. J., Kumar, A., Sato, Y., Lie, P. P., Mohan, P., Coffey, E. E., Kompella, U., Mitchell, C. H., Lloyd-Evans, E., and Nixon, R. A. (2015) Presenilin 1 maintains lysosomal Ca2+ homeostasis via TRPML1 by regulating vATPase-mediated lysosome acidification. Cell Rep 12, 1430-1444

Research Description:

Targeted drug delivery, treatments and diagnostics for cardiovascular diseases

Keywords:

protein engineering, pharmacokinetic modeling, cardiovascular immunology

Research Description:

The Vascular Kinetics Laboratory studies endothelial mechanobiology and treatments that address mechanobiology pathways.

Keywords:

endothelial, mechanobiology, diabetes, shear stress, substrate stiffness, growth factors, extracellular matrix, glucose metabolism

Recent Publications:

Urbano R, Furia C, Basehore S, Morss Clyne A. (2017) Stiff substrates increase inflammation-induced tension and permeability in endothelial monolayers. Biophysical Journal, 113(3): p. 645-655.

Swaminathan S, Ngo O, Basehore S, Morss Clyne A. (2017) A vascular endothelial – breast epithelial cell co-culture model created from 3D cell structures. ACS Biomaterials Science and Engineering, 3(11): p 2999-3006.

Mathew J, Basehore S, Morss Clyne A. (2017) Fluid shear stress and fibroblast growth factor-2 increase endothelial cell-associated vitronectin. Applied Bionics and Biomechanics, Article ID 9040161.

Canver A, Morss Clyne A. (2017) Quantification of multicellular organization, junction integrity, and substrate features in collective cell migration. Microscopy and Microanalysis, 23(1), p. 22-33.

Canver A, Ngo O, Urbano R, Morss Clyne A. (2016) Endothelial cell collective migration depends on substrate stiffness via localized myosin contractility and cell-matrix interactions. Journal of Biomechanics, 49(8): p. 1369-80.

Urbano R, Morss Clyne A. (2016) An inverted dielectrophoretic device for analysis of attached single cell stiffness. Lab on a Chip, 16: p. 561-573.

Mathew J, Morss Clyne A. (2015) Fibroblast growth factor-2 does not rescue plasminogen system activity or capillary-like tube formation in endothelial cells on glycated collagen. Biochemistry and Biophysics Reports, 4: p. 104-110.

Figueroa D, Kemeny S, Morss Clyne A. (2014) Glycated collagen decreased extracellular matrix fibronectin alignment in response to cyclic stretch via interruption of actin alignment. Journal of Biomechanical Engineering, 136(10).

Research Description:

biomaterials, imaging

Recent Publications:

Publications: Roberts, EG, Kleptsyn, VF, Roberts, GD, et al. Development of a bio‐MEMS Device for Electrical and Mechanical Conditioning and Characterization of Cell Sheets for Myocardial Repair. Biotechnology and Bioengineering. 2019; 116: 3098– 3111. https://doi.org/10.1002/bit.27123

Research Description:

Nanoscale Materials Chemistry

Keywords:

Nanoparticles, Nanocrystals, Self-Assembly, Colloids, Quantum Dots, Magnetic Particles

Recent Publications:

Christopher B. Murray‬ - ‪Google Scholar‬

Recent Publications:

1) Targeting drug delivery in the vascular system: Focus on endothelium. Glassman, Patrick M; Myerson, Jacob W; Ferguson, Laura T; Kiseleva, Raisa Y; Shuvaev, Vladimir V; Brenner, Jacob S; Muzykantov, Vladimir R. ADVANCED DRUG DELIVERY REVIEWS 2020.

2) Supramolecular Organization Predicts Protein Nanoparticle Delivery to Neutrophils for Acute Lung Inflammation Diagnosis and Treatment. Myerson, Jacob W; Patel, Priyal N; Habibi, Nahal; Walsh, Landis R; Lee, Yi-Wei; Luther, David C; Ferguson, Laura T; Zaleski, Michael H; Zamora, Marco E; Marcos-Contreras, Oscar A; Glassman, Patrick M; Johnston, Ian; Hood, Elizabeth D; Shuvaeva, Tea; Gregory, Jason V; Kiseleva, Raisa Y; Nong, Jia; Rubey, Kathryn M; Greineder, Colin F; Mitragotri, Samir; Worthen, George S; Rotello, Vincent M; Lahann, Joerg; Muzykantov, Vladimir R; Brenner, Jacob S. BIORXIV 2020.

3) Selective targeting of nanomedicine to inflamed cerebral vasculature to enhance the blood–brain barrier. Marcos-Contreras, Oscar A; Greineder, Colin F; Kiseleva, Raisa Yu; Parhiz, Hamideh; Walsh, Landis R; Zuluaga-Ramirez, Viviana; Myerson, Jacob W; Hood, Elizabeth D; Villa, Carlos H; Tombacz, Istvan; Pardi, Norbert; Seliga, Alecia; Mui, Barbara L; Tam, Ying K; Glassman, Patrick M; Shuvaev, Vladimir V; Nong, Jia; Brenner, Jacob S; Khoshnejad, Makan; Madden, Tom; Weissmann, Drew; Persidsky, Yuri; Muzykantov, Vladimir R. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES 2020.

4) Cross-linker-modulated nanogel flexibility correlates with tunable targeting to a sterically impeded endothelial marker. Myerson, Jacob Wheatley; McPherson, Olivia; DeFrates, Kelsey G; Towslee, Jenna H; Marcos-Contreras, Oscar A; Shuvaev, Vladimir V; Braender, Bruce; Composto, Russell J; Muzykantov, Vladimir R; Eckmann, David M; ACS NANO 2019.

5) Stiffness can mediate balance between hydrodynamic forces and avidity to impact the targeting of flexible polymeric nanoparticles in flow. Farokhirad, Samaneh; Ranganathan, Abhay; Myerson, Jacob; Muzykantov, Vladimir R; Ayyaswamy, Portonovo S; Eckmann, David M; Radhakrishnan, Ravi; NANOSCALE 2019.

6) Red blood cell-hitchhiking boosts delivery of nanocarriers to chosen organs by orders of magnitude. Brenner, Jacob S; Pan, Daniel C; Myerson, Jacob W; Marcos-Contreras, Oscar A; Villa, Carlos H; Patel, Priyal; Hekierski, Hugh; Chatterjee, Shampa; Tao, Jian-Qin; Parhiz, Hamideh; Bhamidipati, Kartik; Uhler, Thomas G; Hood, Elizabeth D; Kiseleva, Raisa Yu; Shuvaev, Vladimir S; Shuvaeva, Tea; Khoshnejad, Makan; Johnston, Ian; Gregory, Jason V; Lahann, Joerg; Wang, Tao; Cantu, Edward; Armstead, William M; Mitragotri, Samir; Muzykantov, Vladimir. NATURE COMMUNICATIONS 2018.

7) Flexible nanoparticles reach sterically obscured endothelial targets inaccessible to rigid nanoparticles. Myerson, Jacob W; Braender, Bruce; Mcpherson, Olivia; Glassman, Patrick M; Kiseleva, Raisa Y; Shuvaev, Vladimir V; Marcos‐Contreras, Oscar; Grady, Martha E; Lee, Hyun‐Su; Greineder, Colin F; Stan, Radu V; Composto, Russell J; Eckmann, David M; Muzykantov, Vladimir R. ADVANCED MATERIALS 2018.

8) Nanoparticle properties modulate their attachment and effect on carrier red blood cells. Pan, Daniel C; Myerson, Jacob W; Brenner, Jacob S; Patel, Priyal N; Anselmo, Aaron C; Mitragotri, Samir; Muzykantov, Vladimir. SCIENTIFIC REPORTS 2018.

9) Mechanisms that determine nanocarrier targeting to healthy versus inflamed lung regions. Brenner, Jacob S; Bhamidipati, Kartik; Glassman, Patrick M; Ramakrishnan, N; Jiang, Depeng; Paris, Andrew J; Myerson, Jacob W; Pan, Daniel C; Shuvaev, Vladimir V; Villa, Carlos H; Hood, Elizabeth D; Kiseleva, Raisa; Greineder, Colin F; Radhakrishnan, Ravi; Muzykantov, Vladimir R. NANOMEDICINE: NANOTECHNOLOGY, BIOLOGY AND MEDICINE 2017.

10) Non-affinity factors modulating vascular targeting of nano-and microcarriers. Myerson, Jacob W; Anselmo, Aaron C; Liu, Yaling; Mitragotri, Samir; Eckmann, David M; Muzykantov, Vladimir R. ADVANCED DRUG DELIVERY REVIEWS 2016.

Keywords:

Nucleic acid-based therapeutics, nano-engineering, targeted delivery of nanomedicine, mRNA therapeutics

Recent Publications:

1. Parhiz H, Brenner JS, Patel PN, Papp TE, Shahnawaz H, Li Q, Shi R, Zamora ME, Yadegari A, Marcos-Contreras OA, Natesan A, Pardi N, Shuvaev VV, Kiseleva R, Myerson JW, Uhler T, Riley RS, Han X, Mitchell MJ, Lam K, Heyes J, Weissman D, Muzykantov VR.: Added to pre-existing inflammation, mRNA-lipid nanoparticles induce inflammation exacerbation (IE). J Control Release April 2022.

2. Rurik JG, Tombácz I , Yadegari A, Fernández P.O.M, Shewale S.V, Li L , Kimura T , Soliman O.U, Papp T.E, Tam Y.K, Mui B.L, Albelda S.M, Puré E , June C.H, AghajanianH , Weissman D., Parhiz H., and Epstein J.A: CAR T cells produced in vivo to treat cardiac injury. Science January 2022.

3. Tombácz I, Laczkó D, Shahnawaz H, Muramatsu H, Natesan A, Yadegari A, Papp T.E., Alameh MG, Shuvaev V, Mui B.L., Tam Y.K., Muzykantov V, Pardi N, Weissman D, Parhiz H: Highly efficient CD4+ T cell targeting and genetic recombination using engineered CD4+ cell-homing mRNA-LNP. Molecular Therapy June 2021.

Research Description:

Organic Chemistry; Polymer Chemistry; Supramolecular Chemistry; Self-Assembly; Self-Organization; Synthetic Biology; Biological Membrane Mimics; Self-Assembling Dendrimers and Dendronized Polymers; Amphiphilic Janus Dendrimers, Glycodendrimers, and Ionizable Dendrimers, Dendrimersomes, Glycodendrimersomes, Dendrimersome Nanoparticles for mRNA Delivery; Ni-Catalyzed Cross-Coupling; Living Chain and Condensation Polymerizations including SET-LRP; Deracemization in Crystal State; Helical Stereoisomers of Poly(arylacetylene)s; Chiral Helical Self-Organizations; Liquid Crystals; Frank-Kasper Phases and Quasicrystals in Soft and Living Matter

Keywords:

Dendrimers; cross-coupling; helical chirality; SET-LRP; Frank-Kasper and quasicrystal phases

Recent Publications:

800 peer reviewed publications; 20 edited books and 1,266 endowed, plenary and invited lectures

Research Description:

Nanoparticles, modified therapeutic drugs/proteins, targeted delivery

Research Description:

Targeted drug delivery

Keywords:

Anti-sense oligonucleotides, neurodegeneration

Recent Publications:

1. Sase S., Almad AA., Boecker CA., Guedes-Dias P., Li JJ., Takanohashi A., Patel A., McCaffrey T., Patel H., Sirdeshpande D., Curiel J., Liu JS., Padiath Q., Holzbaur ELF., Scherer SS., Vanderver A. (2020) TUBB4A mutations result in both glial and neuronal degeneration in an H-ABC leukodystrophy mouse model eLife 9:e52986 https://doi.org/10.7554/eLife.52986

2. Sase, S., Takanohashi, A., Vanderver, A. and Almad, A. (2018), Astrocytes, an active player in Aicardi–Goutières syndrome. Brain Pathology, 28: 399-407. https://doi.org/10.1111/bpa.12600

3. Sase, S., Sase, A., Sialana, F.J., Jr, Gröger, M., Bennett, K.L., Stork, O., Lubec, G. and Li, L. (2015), Individual phases of contextual fear conditioning differentially modulate dorsal and ventral hippocampal GluA1-3, GluN1-containing receptor complexes and subunits. Hippocampus, 25: 1501-1516. https://doi.org/10.1002/hipo.22470

Research Description:

Dr. Sawicki’s laboratory is developing new therapeutic strategies that hold great promise for improving the treatment of metastatic cancer. These strategies are based on the delivery of genetic material, specifically, DNA and siRNA, exclusively to tumor cells, thus protecting healthy cells from damage. Indeed, she was among the first to explore the use of non-viral vectors for the in vivo delivery of DNA.

Recent Publications:

Elevated HuR in Pancreas Promotes a Pancreatitis-like Inflammatory Microenvironment that Facilitates Tumor Development. Peng W, Furuuchi N, Aslanukova L, Huang YH, Brown SZ, Jiang W, Addya S, Vishwakarma V, Peters E, Brody JR, Dixon DA, Sawicki JA. Mol Cell Biol. 2017 Nov 13. doi: 10.1128/MCB.00427-17.

Insights from HuR biology point to potential improvement for second-line ovarian cancer therapy. Huang YH, Peng W, Furuuchi N, DuHadaway JB, Jimbo M, Pirritano A, Dunton CJ, Daum GS, Leiby BE, Brody JR, Sawicki JA. Oncotarget. 2016 Mar 2.

Delivery of Therapeutics Targeting the mRNA-Binding Protein HuR Using 3DNA Nanocarriers Suppresses Ovarian Tumor Growth. Huang YH, Peng W, Furuuchi N, Gerhart J, Rhodes K, Mukherjee N, Jimbo M, Gonye GE, Brody JR, Getts RC, Sawicki JA. Cancer Res. 2016 Mar 15;76(6):1549-59. Epub 2016 Feb 26.

The mRNA-binding protein HuR promotes hypoxia-induced chemoresistance through posttranscriptional regulation of the proto-oncogene PIM1 in pancreatic cancer cells. Blanco FF, Jimbo M, Wulfkuhle J, Gallagher I, Deng J, Enyenihi L, Meisner-Kober N, Londin E, Rigoutsos I, Sawicki JA, Risbud MV, Witkiewicz AK, McCue PA, Jiang W, Rui H, Yeo CJ, Petricoin E, Winter JM, Brody JR. Oncogene. 2015 35(19):2529-41.

HuR Contributes to TRAIL Resistance by Restricting Death Receptor 4 Expression in Pancreatic Cancer Cells. Romeo C, Weber MC, Zarei M, DeCicco D, Chand SN, Lobo AD, Winter JM, Sawicki JA, Sachs JN, Meisner-Kober N, Yeo CJ, Vadigepalli R, Tykocinski ML, Brody JR. Mol Cancer Res. 2016 14(7):599-611.

Research Description:

Drug delivery by therapeutic ultrasound

Keywords:

Therapeutic ultrasound, enhanced vascular permeability, drug delivery, ultrasound and photoacoustic imaging

Recent Publications:

DeOre BJ, Galie PA, Sehgal CM. Fluid flow rate dictates the efficacy of low-intensity anti-vascular ultrasound therapy in a microfluidic model. Microcirculation. 2019 Oct;26(7):e12576. doi: 10.1111/micc.12576. Epub 2019 Aug 4. PubMed PMID: 31140665; PubMed Central PMCID: PMC6819214.

D'Souza JC, Sultan LR, Hunt SJ, Gade TP, Karmacharya MB, Schultz SM, Brice AK, Wood AKW, Sehgal CM. Microbubble-enhanced ultrasound for the antivascular treatment and monitoring of hepatocellular carcinoma. Nanotheranostics. 2019;3(4):331-341. doi: 10.7150/ntno.39514. eCollection 2019. PubMed PMID: 31687321; PubMed Central PMCID: PMC6821993.

Chen Z, Pulsipher KW, Chattaraj R, Hammer DA, Sehgal CM, Lee D. Engineering the Echogenic Properties of Microfluidic Microbubbles Using Mixtures of Recombinant Protein and Amphiphilic Copolymers. Langmuir. 2019 Aug 6;35(31):10079-10086. doi: 10.1021/acs.langmuir.8b03882. Epub 2019 Feb 27. PubMed PMID: 30768278; PubMed Central PMCID: PMC6698903.

D'Souza JC, Sultan LR, Hunt SJ, Schultz SM, Brice AK, Wood AKW, Sehgal CM. B-mode ultrasound for the assessment of hepatic fibrosis: a quantitative multiparametric analysis for a radiomics approach. Sci Rep. 2019 Jun 18;9(1):8708. doi: 10.1038/s41598-019-45043-z. PubMed PMID: 31213661; PubMed Central PMCID: PMC6581954.

Gaffey AC, Chen MH, Trubelja A, Venkataraman CM, Chen CW, Chung JJ, Schultz S, Sehgal CM, Burdick JA, Atluri P. Delivery of progenitor cells with injectable shear-thinning hydrogel maintains geometry and normalizes strain to stabilize cardiac function after ischemia. J Thorac Cardiovasc Surg. 2019 Apr;157(4):1479-1490. doi: 10

Schwartz N, Siegal J, Rourke A, Sehgal CM. Placental Pulsatility: Quantitative Assessment of Placental Bed Vasculature by 2-Dimensional Doppler Cine Imaging. J Ultrasound Med. 2019 Feb;38(2):471-479. doi: 10.1002/jum.14720. Epub 2018 Aug 19. PubMed PMID: 30121962; PubMed Central PMCID: PMC6347511.

Wu T, Sultan LR, Tian J, Cary TW, Sehgal CM. Machine learning for diagnostic ultrasound of triple-negative breast cancer. Breast Cancer Res Treat. 2019 Jan;173(2):365-373. doi: 10.1007/s10549-018-4984-7. Epub 2018 Oct 20. PubMed PMID: 30343454.

Pulsipher KW, Hammer DA, Lee D, Sehgal CM. Engineering Theranostic Microbubbles Using Microfluidics for Ultrasound Imaging and Therapy: A Review. Ultrasound Med Biol. 2018 Dec;44(12):2441-2460. doi: 10.1016/j.ultrasmedbio.2018.07.026. Epub 2018 Sep 19. Review. PubMed PMID: 30241729; PubMed Central PMCID: PMC6643280.

Hajfathalian M, Amirshaghaghi A, Naha PC, Chhour P, Hsu JC, Douglas K, Dong Y, Sehgal CM, Tsourkas A, Neretina S, Cormode DP. Wulff in a cage gold nanoparticles as contrast agents for computed tomography and photoacoustic imaging. Nanoscale. 2018 Oct 21;10(39):18749-18757. doi: 10.1039/c8nr05203d. Epub 2018 Oct 2. PubMed PMID: 30276391; PubMed Central PMCID: PMC6190607.

Sehgal CM, Pulsipher KW, Meng W, Gao C, Hammer DA, Lee D. On-chip generation of monodisperse microbubbles using recombinant protein for ultrasound therapy. American Institute of Ultrasound Annual Conference. 2018 March

Research Description:

We develop molecular and cellular diagnostics and therapeutics. Some of these tools are geared for basic biologic research, while others are clearly translational taking advantage of my groups expertise in nuclear radiology and molecular imaging.

Keywords:

Imaging, PET, Chemical Biology, Synthetic Biology, Nuclear Medicine, Radiotherapeutics

Recent Publications:

Sellmyer MA, Richman SA, Lohith K, Hou C, Weng CC, Mach RH, O'Connor RS, Milone MC, Farwell MD. Imaging CAR T Cell Trafficking with eDHFR as a PET Reporter Gene. Mol Ther. 2020 Jan 8;28(1):42-51. doi: 10.1016/j.ymthe.2019.10.007. Epub 2019 Oct 15. PubMed PMID: 31668558; PubMed Central PMCID: PMC6953896.

Ordonez AA, Sellmyer MA, Gowrishankar G, Ruiz-Bedoya CA, Tucker EW, Palestro CJ, Hammoud DA, Jain SK. Molecular imaging of bacterial infections: Overcoming the barriers to clinical translation. Sci Transl Med. 2019 Sep 4;11(508). doi: 10.1126/scitranslmed.aax8251. Review. PubMed PMID: 31484790; PubMed Central PMCID: PMC6743081.

Sellmyer MA, Lee I, Hou C, Weng CC, Li S, Lieberman BP, Zeng C, Mankoff DA, Mach RH. Bacterial infection imaging with [18F]fluoropropyl-trimethoprim. Proc Natl Acad Sci U S A. 2017 Aug 1;114(31):8372-8377. doi: 10.1073/pnas.1703109114. Epub 2017 Jul 17. PubMed PMID: 28716936; PubMed Central PMCID: PMC5547613.

Sellmyer MA, Lee I, Hou C, Lieberman BP, Zeng C, Mankoff DA, Mach RH. Quantitative PET Reporter Gene Imaging with [11C]Trimethoprim. Mol Ther. 2017 Jan 4;25(1):120-126. doi: 10.1016/j.ymthe.2016.10.018. Epub 2017 Jan 4. PubMed PMID: 28129108; PubMed Central PMCID: PMC5363299.

Sellmyer MA, Bronsart L, Imoto H, Contag CH, Wandless TJ, Prescher JA. Visualizing cellular interactions with a generalized proximity reporter. Proc Natl Acad Sci U S A. 2013 May 21;110(21):8567-72. doi: 10.1073/pnas.1218336110. Epub 2013 May 6. PubMed PMID: 23650381; PubMed Central PMCID: PMC3666728.

Banaszynski LA, Sellmyer MA, Contag CH, Wandless TJ, Thorne SH. Chemical control of protein stability and function in living mice. Nat Med. 2008 Oct;14(10):1123-7. doi: 10.1038/nm.1754. Epub 2008 Sep 28. PubMed PMID: 18836461; PubMed Central PMCID: PMC2605277.

Research Description:

My research is focused on treating developmental and degenerative conditions of the spine and synovial joints. Specifically, we work on targeted therapeutics (protein, small molecules, gene therapy) to treat skeletal disease in lysosomal storage disorders, and age-related intervertebral disc degeneration. This includes the use of biomaterials, microparticles and nanoparticles for sustained and targeted drug delivery. Out research is primarily in the translational space and we make extensive use of preclinical large animal models.

Keywords:

Intervertebral disc, back pain, synovial joint, bone, lysosomal storage disorder, mucopolysaccharidosis

Recent Publications:

1. Lau YK, Peck SH, Arginteanu T, Wu M, Lin M, Shore EM, Klein PS, Casal ML, Smith LJ (2022) Effects of Lithium Administration on Vertebral Bone Disease in Mucopolysaccharidosis I Dogs. Bone. In press. PMID:34695616

2. Zhang C, Gullbrand SE, Schaer TP, Boorman S, Chen W, Elliott DM, Dodge GR, Mauck RL, Malhotra NR, Smith LJ. (2021) Combined Hydrogel and Mesenchymal Stem Cell Therapy for Moderate Severity Disc Degeneration in Goats. Tissue Engineering: Part A. 27:117-128. PMID:32546053

3. Peck SH, Bendigo JR, Tobias JW, Dodge GR, Malhotra NR, Mauck RL, Smith LJ. (2021) Hypoxic preconditioning enhances bone marrow-derived mesenchymal stem cell survival in a low oxygen and nutrient-limited 3D microenvironment. Cartilage. 12:512-525. PMID:30971109

4. Kim DH, Martin JT, Gullbrand SE, Elliott DM, Smith LJ, Smith HE, Mauck RL. (2020) Fabrication, Maturation, and Implantation of Composite Tissue-Engineered Total Discs Formed from Native and Mesenchymal Stem Cell Combinations. Acta Biomaterialia. 114:53-62. PMID:32505801

5. Gullbrand SE, Ashinsky BG, Bonnevie E, Kim DH, Smith LJ, Elliott DM, Schaer TP, Smith HE, Mauck RL. (2018) Long Term In Vivo Mechanical Function and Integration of a Tissue Engineered Intervertebral Disc. Science Translational Medicine. 10:eaau0670. PMID:30463917

Research Description:

Biomaterials and drug delivery systems to modulate immune cell behavior and diagnostics to monitor response to treatment

Keywords:

Immunomodulatory biomaterial, drug delivery, macrophage

Recent Publications:

Pentecost, A.E., S. Jeon, Y. Ko, M. Kim, Y. Gogotsi, K. Kim, K.L. Spiller. “Immunomodulatory nanodiamond particles for the treatment of rheumatoid arthritis.” Regenerative Biomaterials. 2019. 6 (3) 163-174.

Deusenbery, C.B., L. Kalan, J. Meisel, S. Gardner, E. Grice, K.L. Spiller. “Human macrophage response to microbes isolated from diabetic foot ulcers.” Wound Repair and Regeneration, 2019, DOI: 10.1111/wrr.12752

K.L. Wofford, K.C. Cullen, K.L. Spiller. “Modulation of macrophage phenotype via phagocytosis of drug-loaded microparticles.” Journal of Biomedical Materials Research Part A. 2019. DOI: 10.1002/jbm.a.36617

S. Liu+, A. Bajpai+, E.A. Hawthorne, Y. Bae, P. Castagnino, J. Monslow, E. Puré, K.L. Spiller* and Richard K. Assoian*. “Cardiovascular protection in females linked to estrogen-dependent inhibition of arterial stiffening and macrophage MMP12.” JCI Insight 2019 (4) e122742.

J.R. Alhamdi, T. Peng, I.M. Al-Naggar, K.L. Spiller*, L.T. Kuhn*. “Controlled M1-to-M2 transition of aged macrophages by calcium phosphate coatings.” Biomaterials 2019 (196) 90-99.

Bajpai, A., S. Nadkarni, M. Neidrauer, M.S. Weingarten, P.A. Lewin, K.L. Spiller. “Effects of nonthermal, noncavitational ultrasound exposure on human diabetic ulcer healing and inflammatory gene expression.” Ultrasound in Medicine and Biology, 2018, 44 (9) 2043-2049.

Pentecost, A.E., C.E. Witherel, Y. Gogotsi, K.L. Spiller. “Anti-inflammatory effects of octadecylamine-functionalized nanodiamond on primary human macrophages.” Biomaterials Science, 2017, 5: 2131-2143.

Witherel, C.E., T. Yu, M. Concannon, W. Dampier, K.L. Spiller. “Immunomodulatory effects of human cryopreserved viable amniotic membrane in a pro-inflammatory environment in vitro.” Cellular and Molecular Bioengineering, 2017, 10 (5) 451-462.

Witherel, C.E., D. Gurevich, J.D. Collin, P. Martin, K.L. Spiller. “Host-biomaterial interactions in zebrafish.” ACS Biomaterial Science and Engineering, 2017, 4 (4) 1233-1240.

Ferraro, N.M., W. Dampier, M.S. Weingarten, K.L. Spiller. “Deconvolution of Heterogeneous Wound Tissue Samples into Relative Macrophage Phenotype Composition via Models based on Gene Expression.” Integrative Biology, 2017, 9 (4) 328-338.

Research Description:

Professor Stebe is interested in soft, complex fluids, often in settings far from equilibrium from a fundamental and engineering viewpoint. Such systems pervade the therapeutic landscape. In one aspect of her work, she studies the fluid mechanics of surfactant-laden interfaces, dynamic surface tension, wetting phenomena, and Marangoni effects. She is also deeply interested in complex structures which form on fluid interfaces, including protein monolayers, bacterial biofilms and polyelectrolyte films. Recently, she has become interested in particle-laden fluid interfaces and how interactions that arise at interfaces can be used to steer particles into well-defined structures at fluid interfaces or on lipid bilayers. Finally, a major effort in her research group focuses on developing strategies for soft reconfigurable systems by exploiting stresses in soft systems and geometric cues.

Keywords:

surface tension, nanoparticle, capsule, vesicle, colloids, liquid crystals, adhesion, adsorption, monolayers, films

Comments:

Temple University School of Pharmacy

Research Description:

Peptide design and self-assembly

Extracellular matrix-inspired biomaterials

Self-assembled polymer nanostructures

Protein nanostructures

Drug and gene delivery for regenerative medicine and cancer

Synthetic cell engineering

Keywords:

Gene delivery, drug delivery, biomaterials, regenerative medicine, wound healing, targeted therapy, peptide design

Recent Publications:

https://scholar.google.com/citations?user=Jbclv7UAAAAJ&hl=en&oi=ao

Research Description:

Therapeutic ultrasound, translational cancer research, quantitative ultrasound imaging, photo acoustic imaging

Keywords:

ultrasound, cancer therapy, cancer imaging

Recent Publications:

Sultan L, Sehgal C. A review of early experience in lung ultrasound (LUS) in the diagnosis and management of COVID-19. Ultrasound Med Biol. 2020 May; NIHMSID: NIHMS7247506.doi: 10.1016/j.ultrasmedbio.2020.05.012.

Sultan LR, Xiong H, Zafar HM, Schultz SM, Langer JE, Sehgal CM. Vascularity assessment of thyroid nodules by quantitative color Doppler ultrasound. Ultrasound Med Biol. 2015 May;41(5):1287-93. doi: 10.1016/j.ultrasmedbio.2015.01.001. Epub 2015 Feb 9. PubMed PMID: 25677641.

D'Souza JC, Sultan LR, Hunt SJ, Gade TP, Karmacharya MB, Schultz SM, Brice AK, Wood AKW, Sehgal CM. Microbubble-enhanced ultrasound for the antivascular treatment and monitoring of hepatocellular carcinoma. Nanotheranostics. 2019;3(4):331-341. doi: 10.7150/ntno.39514. eCollection 2019. PubMed PMID: 31687321; PubMed Central PMCID: PMC6821993.

D'Souza JC, Sultan LR, Hunt SJ, Schultz SM, Brice AK, Wood AKW, Sehgal CM. B-mode ultrasound for the assessment of hepatic fibrosis: a quantitative multiparametric analysis for a radiomics approach. Sci Rep. 2019 Jun 18;9(1):8708. doi: 10.1038/s41598-019-45043-z. PubMed PMID: 31213661; PubMed Central PMCID: PMC6581954.

L. R. Sultan, S. M. Schultz, T. W. Cary, C. M. Sehgal. Machine Learning to Improve Breast Cancer Diagnosis by Multimodal Ultrasound. 2018 IEEE International Ultrasonics Symposium (IUS). 2018; :1-4. doi: 10.1109/ULTSYM.2018.8579953.

Wu T, Sultan LR, Tian J, Cary TW, Sehgal CM. Machine learning for diagnostic ultrasound of triple-negative breast cancer. Breast Cancer Res Treat. 2019 Jan;173(2):365-373. doi: 10.1007/s10549-018-4984-7. Epub 2018 Oct 20. PubMed PMID: 30343454.

Research Description:

Developing targeted imaging and therapeutic agents with a particular focus on nanomedicine, biologics, and bioconjugate chemistry.

Keywords:

Molecular imaging, site-specific bioconjugations, antibody conjugates, nanomedicine, nanoparticles, bispecific antibodies.

Research Description:

I run a dermatology bioengineering laboratory focused on polymer-based biomaterials for drug delivery and tissue engineering, with interests in wound healing, autoimmune disease, and hair loss

Keywords:

hydrogels, biomaterials, polymers, wound healing, dermatology

Recent Publications:

Wang LL,* Tuohy S, Nace A, Xu KL, Zheng Y, Yang R, Burdick JA, Cotsarelis G. Local and sustained baricitinib delivery to the skin through injectable hydrogels containing reversible thioimidate adducts. Advanced Healthcare Materials, 2024: e2303256.

Uman S, Wang LL, Thorn SL, Liu Z, Duncan JS, Sinusas AJ, Burdick JA. Imaging of Injectable Hydrogels Delivered into Myocardium with SPECT/CT. Advanced Healthcare Materials, 2020;2000294.

Wang LL, Cotsarelis G. Regenerative medicine: Hair-bearing skin grown in a dish. Nature, 2020;582(7812):343-344.

Chung JJ, Han JJ, Wang LL, Arisi MF, Zaman S, Gordon J, Li E, Chen CW, Gaffey AC, Burdick JA, Atluri P. Delayed delivery of endothelial progenitor cell derived extracellular vesicles via shear-thinning gel improves post-infarct hemodynamics. Journal of Thoracic and Cardiovascular Surgery, 2019;129(5):1825-1835

Wang LL, Chung JJ, Li EC, Uman S, Atluri P, Burdick JA. Injectable and protease-degradable hydrogel for siRNA sequestration and triggered delivery to the heart. Journal of Controlled Release, 2018; 285(10)152-161.

Wang LL, Highley CB, Yeh YC, Galarraga JH, Uman S, Burdick JA. Three-dimensional extrusion bioprinting of single- and double-network hydrogels containing dynamic covalent crosslinks. Journal of Biomedical Materials Research Part A, 2018;106(4):865-875.

Wang LL, Liu Y, Chung JJ, Wang T, Gaffey AC, Lu M, Cavanaugh CA, Zhou S, Kanade R, Atluri P, Morrisey EE, Burdick JA. Sustained miRNA delivery from an injectable hydrogel promotes cardiomyocyte proliferation and functional regeneration after ischaemic injury. Nature Biomedical Engineering, 2017;1:983-992.

Wang LL, Sloand JN, Gaffey AC, Venkataraman CM, Wang Z, Trubelja A, Hammer DA, Atluri P, Burdick JA. Injectable, guest-host assembled polyethylenimine hydrogel for siRNA delivery. Biomacromolecules, 2017;18(1):77-86.

Research Description:

Research in our lab lies at the interface of chemistry and biology, with an eye towards understanding and treating human diseases. We use interdisciplinary approaches such as organic synthesis, chemical proteomics, protein engineering, chemical sensing, and molecular imaging to investigate the biological mechanisms underlying diseases such as cancer, inflammation, and immune disorders. In particular, we are interested in developing innovative probes to systematically dissect proteins essential for the onset and relapse of diseases. We are also actively pursuing the design and synthesis of novel diagnostics and targeted therapeutics, using our expertise in protein engineering, organic synthesis, drug delivery, library screening, and cell assay. Students have the opportunity to work in may areas spanning from organic synthesis to molecular biology/cell biology. The training is expected to help students achieve multiple skill sets and a strong publication record.

Keywords:

Chemical Biology, Protein Engineering, Organic Synthesis, Molecular Imaging, Targeted Therapeutics, Cancer, Inflammatory Disorders

Research Description:

nucleoside-modified mRNA in lipid nanoparticle therapeutics

Keywords:

pseudouridine, mRNA, vaccine, lipid nanoparticle

Research Description:

Ultrasound contrast agents, drug a siRNA delivery, spinal cord injury

Keywords:

Contrast agents, ultrasound, drug delivery, spinal cord injury, siRNA

Research Description:

During chronic infections and cancer, CD8 T cells become dysfunctional and fail to form functional memory, a process described as “exhaustion”. Key features of T cell exhaustion include increased expression of inhibitory receptors, reduced cytokine production, weakened cell proliferation potential and altered transcriptional program/epigenetic landscape. Our lab is interested in the population dynamics, transcriptional/epigenetic stochastic and molecular regulation mechanism during T cell exhaustion development. By understanding these mechanisms, we aim to enhance T cell immunity and provide better therapeutic strategies for clinical application.

Keywords:

Immunity, T cell exhaustion, Cancer Immunotherapy, Vaccines, Therapeutics

Recent Publications:

1. Bengsch B, Ohtani T, Khan O, Setty M, Manne S, O'Brien S, Gherardini PF, Herati RS, Huang AC, Chang KM, Newell EW, Bovenschen N, Pe'er D, Albelda SM, Wherry EJ. 2018. Epigenomic-Guided Mass Cytometry Profiling Reveals Disease-Specific Features of Exhausted CD8 T Cells. Immunity. 2018 May 15;48(5):1029-1045.e5. doi: 10.1016/j.immuni.2018.04.026. PMID: 29768164

2. Huang, A.C., Postow, M.A., Orlowski, R.J., Mick, R., Bengsch, B., Manne, S., Xu, W., Harmon, S., Adamow, M., Kuk, D., Panageas, K., Carrera, C., Wong, P., Quagliarello, F., Pauken, K.E., Herati, R.S., McGettigan, S., Kothari, S., George, S.M., Wenz, B., D’Andrea, K., Xu, X., Amaravadi, R.K., Karakousis, G.C., Schuchter, L.M., Nathanson, K.L., Wolchok, J.D., Gangadhar, T.C., and Wherry, E.J. 2017. Blood immune profiling of anti-PD-1 1 therapy in human melanoma reveals a link between T cell re-invigoration and tumor burden that predicts response. Nature. 545(7652):60-65. doi:10.1038/nature22079. PMID: 28397821

3. Pauken, K.E., Odorizzi, P.M., Sammons, M.A., Manne, S.K., Godec, J., Khan, O., Sen, D., Kurachi, M., Barnitz, R.A., Bengsch, B., Huang, A.C., Schenkel, J.M., Vahedi, G., Haining, W.N., Berger, S.L., Wherry, E.J. 2016. Impact of PD-1 blockade on epigenetic and transcriptional reprogramming of exhausted T cells. Science. 354(6316):1160-1165. PMID: 27789795

4. Odorizzi, P.M., Pauken, K.E., Paley, M.A., Sharpe, A.H., and Wherry, E.J. 2015. Genetic absence of PD-1 promotes accumulation of terminally-differentiated exhausted CD8+ T cells. J. Exp. Med. 12(7):1125-37. PMID: 26034050.

5. Crawford, A., Angelosanto, J.M., Doering, T.A., Kao, C., Wherry, E.J. 2014. Molecular and transcriptional basis of CD4 T cell dysfunction during chronic infection. Immunity. 40(2):289-302. PMID: 24530057

6. Paley, M.A., Kroy, D.C., Dolfi, D.V., Bikoff, E., Robertson, E.J., Lauer, G.M., Reiner, S.L., Wherry, E.J. 2012. Key role for balancing progenitor and terminal subsets of exhausted T cells during chronic infection. Science. 338(6111):1220-5. PMID: 23197535.

7. Doering, T.A., Crawford, A., Angelosanto, J.M., Paley, M.A., Wherry, E.J. 2012. Defining the transcriptional networks of CD8+ T cell memory versus exhaustion. Immunity. 37(6):1130-44. PMID: 23159438.

8. Blackburn, S.D., Shin, H., Haining, W.N., Zou, T., Workman, C.J., Polley, A., Betts, M.R., Freeman, G.J., Vignali, D.A.A., Wherry, E.J. 2009. Co-regulation of CD8 T cell exhaustion during chronic viral infection by multiple inhibitory receptors. Nat. Immunol. 10:29-37. PMID: 19043418

9. Blackburn, S.D., Shin, H., Freeman, G.J., Wherry, E.J. 2008. Selective Expansion of a Subset of Exhausted CD8 T cells by aPD-L1 Blockade. PNAS 105:15016-15021. PMID: 18809920

10. Wherry, E.J., Kaech, S.M., Haining, W.N., Subramaniam,, S., Blattman,, J.N., Barber, D.L., Ahmed, R. 2007. Molecular Signature of CD8 T Cell Exhaustion during Chronic Viral Infection. Immunity. 27:670-84. PMID: 17950003

Research Description:

Identification of targets of anesthesia, molecular mechanisms of anesthesia, development of new probes for target identification, small molecule therapeutics, pre-clinical and translational research

Keywords:

anesthesia, antagonism, mechanisms, proteomics, propofol, volatile anesthetics, etomidate

Research Description:

gene and stem cell therapies for neurological diseases

Research Description:

Nanodelivery of therapeutic or imaging agents for treatment or diagnosis of drug-resistant cancers and infectious diseases.

Research Description:

My research focus is targeting therapy on ovarian cancers, majorly DNA damage and cell cycle regulator inhibitors in targeting ovarian cancers with specific genes mutations or amplification.

Keywords:

Targeting therapy, Ovarian cancer, DNA damage

Recent Publications:

Xu H#, George E#, Kinose Y, Kim H, Shah JB, Peake JD, Ferman B, Medvedev S, Murtha T, Barger CJ, Devins KM, D'Andrea K, Wubbenhorst B, Schwartz LE, Hwang WT, Mills GB, Nathanson KL, Karpf AR, Drapkin R, Brown EJ, Simpkins F : CCNE1 copy number is a biomarker for response to combination WEE1-ATR inhibition in ovarian and endometrial cancer models. Cell Rep Med 2(9): 100394, 2021 Notes: (# Equal Contribution).

Kim H#, Xu H#, George E, Hallberg D, Kumar S, Jagannathan V, Medvedev S, Kinose Y, Devins K, Verma P, Ly K, Wang Y, Greenberg RA, Schwartz L, Johnson N, Scharpf RB, Mills GB, Zhang R, Velculescu VE, Brown EJ, Simpkins F : Combining PARP with ATR inhibition overcomes PARP inhibitor and platinum resistance in ovarian cancer models. Nat Commun 11(1): 3726, 2020 Notes: (# Equal Contribution).

Gitto SB, Kim H, Rafail S, Omran DK, Medvedev S, Kinose Y, Rodriguez-Garcia A, Flowers AJ, Xu H, Schwartz LE, Powell DJ Jr, Simpkins F: An autologous humanized patient-derived-xenograft platform to evaluate immunotherapy in ovarian cancer. Gynecol Oncol 156(1): 222-232, 2020.

Liu T#, Ma W#, Xu H#, Huang M, Zhang D, He Z, Zhang L, Brem S, O'Rourke DM, Gong Y, Mou Y, Zhang Z, Fan Y: PDGF-mediated mesenchymal transformation renders endothelial resistance to anti-VEGF treatment in glioblastoma. Nat Commun 9(1): 3439, 2018 Notes: (# Equal Contribution).

Liu T#, Xu H#, Huang M, Ma W, Saxena D, Lustig RA, Alonso-Basanta M, Zhang Z, O'Rourke DM, Zhang L, Gong Y, Kao GD, Dorsey JF, Fan Y: Circulating Glioma Cells Exhibit Stem Cell-like Properties. Cancer Res 78(23): 6632-6642, 2018 Notes: (# Equal Contribution).

Wang Q, He Z, Huang M, Liu T, Wang Y, Xu H, Duan H, Ma P, Zhang L, Zamvil SS, Hidalgo J, Zhang Z, O'Rourke DM, Dahmane N, Brem S, Mou Y, Gong Y, Fan Y: Vascular niche IL-6 induces alternative macrophage activation in glioblastoma through HIF-2alpha. Nat Commun 9(1): 559, 2018.

Wang Y, Xu H, Liu T, Huang M, Butter PP, Li C, Zhang L, Kao GD, Gong Y, Maity A, Koumenis C, Fan Y: Temporal DNA-PK activation drives genomic instability and therapy resistance in glioma stem cells. JCI Insight 3(3), 2018.

Keywords:

nanoparticles, targeted delivery, lipid synthesis

Research Description:

Synthesis and assembly of polymer nanoparticles for controlled encapsulation and release of drugs; creating anti-fouling surfaces; synthesis of magnetic, light, heat and piezelectrically responsive nano-/microparticles and polymer composites and their actuation; design of wearable electronics.

Keywords:

polymer nanoparticles, drug delivery, anti-fouling, responsive nano-/microparticles, 3D scaffolds, wound dressing films and pastes.

Recent Publications:

1. Chen, Mingtao; Wu, Yue; Chen, Baohong; Tucker, Alexander M.; Jagota, Anand and Yang, Shu*, “Fast, strong, and reversible adhesives with dynamic covalent bonds for potential use as wound dressing adhesives”, Proc. Nat. Acad. Sci. USA, 2022, 119 (29), 2203074119.

2. McGann, Carolyn M. †; Lee, Young-Joo†; Kim, Se-Um†; Weinberg, Danielle D.†; Zha, Xincheng; Huber, Matthew; Hast, Michael W.; Dear, Kayley; Nadkarni, Vinay; Foglia, Elizabeth E.*; Yang, Shu*,“Reverse-engineered Highly Conformable, Leak and Pressure Reducing Cushion for Neonatal Resuscitation Mask”, Adv. Mater. Tech. 2021, 2101364.

3. Liu, Xilin; Zhu, Hongjie; Qiu, Tian; Wu, Xiaotie; Zhang, Milin; Richardson, Andrew G.; Sritharan, Srihari Y.; Ge, Dengteng; Yang, Shu; Lucas, Timothy H.; Engheta, Nader; Van der Spiegel, Jan*, “A Fully Integrated Sensor-Brain-Machine Interface System for Restoring Somatosensation”, IEEE Sensors J., 2021, 12 (4), 50844–50851.

4. Honglawan, A., Ni, H., Weissman, D. and Yang, S.*, " Synthesis of Random Copolymer Based pH-Responsive Nanoparticles as Drug Carriers for Cancer Therapeutics”, Polym. Chem., 2013, 4 (13), 3667 - 3675.

5. Fargnoli, A. S., Mu, A., Katz, M. G., Williams, R. D., Margulies, K. B., Weiner, D. B., Yang, S. and Bridges, C. R., "Anti-inflammatory Loaded Poly-Lactic Glycolic Acid Nanoparticle Formulations to Enhance Myocardial Gene Transfer: An In-Vitro Assessment of a Drug/Gene Combination Therapeutic Approach for Direct Injection", J. Translational Medicine, 2014, 12, 171.

6. Qin, S., Geng, Y. Discher, D. E.* and Yang, S.*, “ Temperature-Controlled Assembly and Release from Polymer Vesicles of Poly(ethylene oxide)-block-poly(N-isopropylacrylamide)”, Adv. Mater., 2006, 18 , 2905-2909.

Research Description:

My research is focused on development of biomaterial-based drug delivery systems and therapeutic nanoparticles (with and without drugs) for neural, cardiovascular, and cancer treatments.

Keywords:

biomaterial, drug delivery, nanoparticles, tissue engineering, hydrogel, stem cells.

Recent Publications:

1. Zhang T, Nong J, Alzahrani N, Wang Z, Meier T, Yang DG, Ke Y, Zhong Y*, Fu J*. “Self-Assembly of DNA Minocycline Complexes by Metal Ions with Controlled Drug Release”. ACS Applied Materials & Interfaces. 11: 29512-29521, 2019. *Co-corresponding authors

2. Ghosh B, Nong J, Wang Z, Urban MW, Heinsinger NM, Trovillion VA, Wright MC, Lepore AC*, Zhong Y*. “A hydrogel engineered to deliver minocycline locally to the injured cervical spinal cord protects respiratory neural circuitry and preserves diaphragm function”. Neurobiology of Disease. 127:591-604, 2019. *Co-corresponding authors

3. Ghosh B., Wang Z., Nong J., Urban M.W., Zhang Z., Trovillion V.A., Wright M.C., Zhong Y.*, & Lepore A.C.* “Local BDNF Delivery to the Injured Cervical Spinal Cord using an Engineered Hydrogel Enhances Diaphragmatic Respiratory Function”. The Journal of Neuroscience, 38, 5982-5995, 2018. *Co-corresponding authors

4. Niu X, Zhang Z, Zhong Y*. “Hydrogel loaded with self-assembled dextran sulfate-doxorubicin complexes as a delivery system for chemotherapy”. Materials Science and Engineering C. 77:888-894, 2017.

5. Shultz RB, Wang Z, Nong J, Zhang Z, and Zhong Y*. “Local delivery of thyroid hormone promotes oligodendrocyte differentiation and myelination after spinal cord injury”. Journal of Neural engineering, 12(5):702-713, 2017

6. Wang Z, Nong J, Shultz RB, Zhang Z, Tom VJ, Ponnappan RK, and Zhong Y*. “Local delivery of minocycline from metal ion-assisted self-assembled complexes promotes neuroprotection and functional recovery after spinal cord injury”. Biomaterials. 112: 62-71, 2017.

7. Zhang Z, Li Q, Han L, and Zhong Y*. “Layer-by-Layer Films Assembled from Natural Polymers for Sustained Release of Neurotrophin”, Biomedical Materials. 10(5): 055006, 2015.

8. Zhang Z, Nong J, and Zhong Y*. “Antibacterial, anti-inflammatory and neuroprotective layer-by-layer coatings for neural implants”, Journal of Neural Engineering. 12(4):046015, 2015.

9. Zhang Z, Wang Z, Nong J, Nix CA, Ji HF, and Zhong Y*. “Metal ion-assisted self-assembly of complexes for controlled and sustained release of minocycline for biomedical applications”, Biofabrication. 7(1): 015006, 2015.

10. Zhang Z, Nix CA, Gerstenhaber JA, and Zhong Y*. “Calcium binding-mediated sustained release of minocycline from hydrophilic multilayer coatings targeting infection and inflammation for medical implants”. PLoS One. 9(1): e84360, 2014.

Research Description:

Magnetic resonance imaging (MRI) and spectroscopy (MRS). Developing imaging markers (MRI/S and PET) of metabolic signatures of cancer and heart failure. Developing in vivo imaging markers for assessing therapeutic responses. Stem cells and cardiac repair.

Recent Publications:

Cao J, Pickup S, Clendenin C, Blouw B, Choi H, Kang D, Rosen MA, O'Dwyer PJ and Zhou R : Dynamic contrast-enhanced MRI detects responses to stroma-directed therapy in mouse models of pancreatic ductal adenocarcinoma. Clinical Cancer Research 25(7):: 2314-2322, Dec 2018