Center for Targeted Therapeutics and Translational Nanomedicine (CT³N)

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Academic Members

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A

Kalil Abdullah, MD

Instructor, Department of Neurosurgery Perelman School of Medicine University of Pennsylvania

kalil.abdullah@uphs.upenn.edu
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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.

Abass Alavi, MD, PhD, DSc

Department of Radiology, Hospital of the University of Pennsylvania

abass.alavi@uphs.upenn.edu

Steven M. Albelda, MD

Department of Medicine, Perelman School of Medicine, Penn

ALBELDA@pennmedicine.UPENN.EDU

Alexey Aprelev, PhD

Department of Physics, Drexel Univeristy

aprelev@drexel.edu

Portonovo S. Ayyaswamy, PhD

School of Engineering and Applied Science, Penn

ayya@seas.upenn.edu

B

Hamid Bassiri, MD, PhD

Department of Pediatrics, CHOP/Perelman School of Medicine, Penn

bassiri@email.chop.edu

Dawn A. Bonnell, PhD

School of Engineering and Applied Science, Penn

bonnell@lrsm.upenn.edu

Garrett M. Brodeur, MD

Department of Pediatrics, CHOP/Perelman School of Medicine, Penn

brodeur@email.chop.edu

Jason A. Burdick, PhD

School of Engineering and Applied Science, Penn

burdick2@seas.upenn.edu

Theresa M. Busch, PhD

Department of Radiology, Perelman School of Medicine, Penn

buschtm@pennmedicine.upenn.edu

C

Robert W. Carpick, PhD

John Henry Towne Professor and Department Chair, Department of Mechanical Engineering and Applied Mechanics, School of Engineering and Applied Science, Penn

carpick@seas.upenn.edu
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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

Martin P. Carroll, MD

Hospital of the University of Pennsylvania / Department of Medicine, Penn

carroll2@mail.med.upenn.edu

I-Wei Chen, PhD

School of Engineering and Applied Science, Penn

iweichen@seas.upenn.edu

Hao Cheng, PhD

Assistant Professor, Materials Science and Engineering Department, Drexel University

hcheng@drexel.edu
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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

Zhiliang Cheng, PhD

School of Engineering and Applied Science, Penn

zcheng@seas.upenn.edu

Michael Chorny, PhD

Associate Professor of Pediatrics, Department of Pediatrics, The Children's Hospital of Philadelphia and The University of Pennsylvania School of Medicine

chorny@email.chop.edu
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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

Douglas B. Cines, MD

Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania

dcines@mail.med.upenn.edu

Akiva S. Cohen, PhD

Department of Pediatrics, CHOP/Perelman School of Medicine, Penn

cohena@email.chop.edu

Russell J. Composto, PhD

School of Engineering and Applied Science, Penn

composto@lrsm.upenn.edu

David P. Cormode, DPhil

Department of Radiology, Hospital of the University of Pennsylvania

david.cormode@uphs.upenn.edu
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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.

Keywords:

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

Recent Publications:

Cormode, David P.; Si-Mohamed, Salim; Bar-Ness, Daniel; Sigovan, Monica; Naha, Pratap C.; Balegamire, Joelle; Lavenne, Franck; Coulon, Philippe; Roessl, Ewald; Bartels, Matthias; Rokni, Michal; Blevis, Ira; Boussel, Loic; Douek, Philippe: Multicolor spectral photon-counting computed tomography: in vivo dual contrast imaging with a high count rate scanner. Scientific Reports 7: 4784, July 2017.

Chhour, Peter; Kim, Johoon; Benardo, Barbara; Tovar, Alfredo; Mian, Shaameen; Litt, Harold I.; Ferrari, Victor A.; Cormode, David P.: Effect of gold nanoparticle size and coating on labeling monocytes for CT tracking. Bioconjugate Chemistry 28(1): 260-269, January 2017 Notes: Part of a special issue: Interfacing Inorganic Nanoparticles with Biology.

Naha, Pratap C.; Lau, Kristen C.; Hsu, Jessica, C.; Hajfathalian, Maryam; Mian, Shaameen; Chhour, Peter; Uppulari, Lahari; MacDonald, Elizabeth S.; Maidment, Andrew D. A.; Cormode, David P.: Gold silver alloy nanoparticles (GSAN): an imaging probe for breast cancer screening with dual-energy mammography or computed tomography. Nanoscale 8: 13740–13754, September 2016.

Cheheltani, Rabee; Ezzibdeh, Rami M.; Chhour, Peter; Chandrika, Kumudini; Jurcova, Martina; Blundell, Cassidy; Litt, Harold I.; Ferrari, Victor A.; Allcock, Harry A.; Sehgal, Chandra M.; Cormode, David P. : Tunable, biodegradable gold nanoparticles as contrast agents for computed tomography and photoacoustic imaging. Biomaterials 102: 87-97, September 2016.

Bernstein, Ally L.; Dhanantwari, Amar; Jurcova, Martina; Cheheltani, Rabe’e; Naha, Pratap C.; Ivanc, Thomas; Shefer, Efrat; Cormode, David P.: Effect of iterative model-based reconstruction on the sensitivity of computed tomography towards iodine and gold nanoparticle contrast agents. Scientific Reports 6: 26177, May 2016.

Chhour, Peter; Naha, Pratap C.; O’Neill, Sean M.; Litt, Harold I.; Reilly, Muredach P.; Ferrari, Victor A.; Cormode, David P.: Labeling monocytes with gold nanoparticles to track their recruitment in atherosclerosis with computed tomography. Biomaterials 82: 93-103, May 2016.

Naha, Pratap C.; Chhour, Peter; Cormode, David P.: Systematic in vitro toxicological screening of gold nanoparticles designed for nanomedicine applications. Toxicology in Vitro 29: 1445-1453, October 2015.

Naha, Pratap C.; Al-Zaki, Ajlan; Hecht, Elizabeth; Chorny, Michael; Chhour, Peter; Blankemeyer, Erik; Yates, Douglas M.; Witschey, Walter W. T.; Litt, Harold I.; Tsourkas, Andrew; Cormode, David P.: Dextran coated bismuth-iron oxide nanohybrid contrast agents for computed tomography and magnetic resonance imaging. J. Mater. Chem. B 2(46): 8239-8248, November 2014.

Chhour, Peter; Gallo, Nicolas; Cheheltani, Rabe’e; Williams, Dewight; Al-Zaki, Ajlan; Nichol, Jessica L.; Tian, Zhicheng; Paik, Taejong; Naha, Pratap C.; Witschey, Walter W. T.; Allcock, Harry R.; Murray, Chris B.; Tsourkas, Andrew; Cormode, David P.: Nano-disco balls: Control over surface versus core loading of diagnostically active nanocrystals into polymer nanoparticles. ACS Nano 8(9): 9143-9153, September 2014.

Brown, Anna L.; Naha, Pratap C.; Litt, Harold I.; Goforth, Andrea M. Cormode, David P.: Synthesis, X-ray Opacity, and Biological Compatibility of Ultra-High Payload Elemental Bismuth Nanoparticle X-ray Contrast Agents. Chemistry of Materials 26: 2266-2274, April 2014.

George Coukos, MD, PhD

Perelman School of Medicine, Penn

gcks@mail.med.upenn.edu

D

Anil P. D'Mello, PhD

Department of Pharmaceutical Sciences, University of the Sciences

a.dmello@usciences.edu

Henry Daniell, PhD

Department of Biochemistry, Penn School of Dental Medicine

hdaniell@upenn.edu

Peter F. Davis, PhD

Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania

pfd@pennmedicine.upenn.edu

Emily Day, PhD

Assistant Professor, Assistant Professor, Department of Biomedical Engineering, University of Delaware

emilyday@udel.edu
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Research Description:

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

Keywords:

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

Recent Publications:

1. Riley RS, Day ES. Frizzled7 antibody-functionalized nanoshells enable multivalent binding for Wnt signaling inhibition in triple negative breast cancer cells. Small. 2017; In press.

2. Riley RS, Day ES. Gold nanoparticle-mediated photothermal therapy: applications and opportunities for multimodality cancer treatment. WIRES Nanomedicine & Nanobiotechnology. 2017; e1449.

3. Melamed JR, Riley RS, Valcourt DM, Day ES#. Using gold nanoparticles to disrupt the tumor microenvironment: an emerging therapeutic strategy. ACS Nano. 2016; 10(12): 10631-10635.

4. Fay BL, Melamed JR, Day ES#. Nanoshell-mediated photothermal therapy can enhance chemotherapy in inflammatory breast cancer cells. International Journal of Nanomedicine. 2015; 10: 6931-6941.

5. Kouri FM, Hurley, LA, Daniel WL, Day ES, Hua Y, Hao L, Peng C-Y, Merkel TJ, Queisser MA, Ritner C, Zhang H, James CD, Sznajder JI, Chin L, Giljohann DA, Kessler JA, Peter ME, Mirkin CA, Stegh AH. miR-182 integrates apoptosis, growth, and differentiation programs in glioblastoma. Genes & Development. 2015; 29(7): 732-745.

6. Melamed JR*, Edelstein RS*, Day ES#. Elucidating the fundamental mechanisms of cell death triggered by photothermal therapy. ACS Nano. 2015; 9(1): 6-11. *Contributed equally.

7. Jensen SA*, Day ES*, Ko CH*, Hurley LA, Luciano JP, Kouri FM, Merkel TJ, Luthi AJ, Patel PC, Cutler JI, Daniel WL, Scott AW, Rotz MW, Meade TJ, Giljohann DA, Mirkin CA, Stegh AH. Spherical nucleic acid nanoparticle conjugates as an RNAi-based therapy for glioblastoma. Science Translational Medicine. 2013; 5(209): 209ra152.

Cesar De la Fuente

Presidential Assistant Professor Leader, Machine Biology Group Institute for Biomedical Informatics Institute for Biomedical Informatics, Institute for Translational Medicine and Therapeutics Dept. of Bioengineering Depts. of Microbiology and Psychiatry, Perelman School of Medicine University of Pennsylvania

cfuente@pennmedicine.upenn.edu
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Recent Publications:

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

Edward J. (Jim) Delikatny, PhD

Perelman School of Medicine, Penn

delikatn@mail.med.upenn.edu

Scott L. Diamond, PhD

School of Engineering and Applied Science and Institute of Medicine & Engineering, Penn

sld@seas.upenn.edu

Dennis E. E. Discher, PhD

Director of NCI Phys Sci Oncology Ctr @ Penn, School of Engineering and Applied Science, Penn

discher@seas.upenn.edu
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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.

Ivan J. Dmochowski, PhD

Department of Chemistry, School of Arts and Sciences, Penn

ivandmo@sas.upenn.edu

E

James H. Eberwine, PhD

Department of Pharmacology, Perelman School of Medicine, Penn

eberwine@upenn.edu

David M. Eckmann, PhD, MD

Department of Anesthesiology and Critical Care, Perelman School of Medicine, Penn

eckmanndm@uphs.upenn.edu

Karin T.S. Eisinger, PhD

Department of Pathology and Laboratory Medicine, Penn

karineis@mail.med.upenn.edu

F

Yi Fan, MD, PhD

Assistant Professor, Department of Radiation Oncology

yi.fan@uphs.upenn.edu
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.

Cormac T. Farrelly, MD

Department of Radiology, Abramson Cancer Center

Giovanni Ferrari, PhD

Department of Surgery, Perelman School of Medicine, Penn

giovanni.ferrari@uphs.upenn.edu

Conroy Field

PhD Student, Pharmacology Graduate Group, Pharmacology Graduate Group

fieldco@pennmedicine.upenn.edu

Ilia Fishbein, MD, PhD

Department of Pediatrics, CHOP/Perelman School of Medicine, Penn

fishbein@email.chop.edu

Garret FitzGerald, MD, FRS

Department of Pharmacology, Perelman School of Medicine, Penn

garret@upenn.edu

G

Terence P. Gade, MD, PhD

Department of Radiology, Perelman School of Medicine, Penn

Terence.Gade@uphs.upenn.edu

Jerry D. Glickson, PhD

Department of Radiology, Perelman School of Medicine, Penn

glickson@mail.med.upenn.edu

Robert C. Gorman, MD

Gorman Cardiovascular Research Group, Perelman School of Medicine, Penn

gormanr@uphs.upenn.edu

Riccardo Gottardi, Ph.D.

Assistant Professor, Department of Pediatrics, Children's Hospital of Philadelphia Department of Pediatrics, Perelman School of Medicine Department of Bioengineering, School of Engineering and Applied Sciences

gottardir@email.chop.edu
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Research Description:

Controlled Drug Delivery System

Synthetic materials to direct cell fate

Keywords:

drug delivery, polymers, synthetic materials, stem cells

Anthony P. Green, PhD

The Nanotechnology Institute and Ben Franklin Technology Partners of Southeastern Pennsylvania

anthony@sep.benfranklin.org

Roger A. Greenberg, MD, PhD

Department of Cancer Biology, AFCRI, PSOM, Penn

rogergr@mail.med.upenn.edu

H

Daniel A. Hammer, PhD

School of Engineering and Applied Science, Penn

hammer@seas.upenn.edu

John Higgins, PhD

Executive Director, Merck

john_higgins3@merck.com
Keywords:

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

John B. Hogenesch, PhD

Department of Pharmacology, Perelman School of Medicine, Penn

hogenesc@mail.med.upenn.edu

David Holt, BVSc

School of Veterinary Medicine, Penn

dholt@vet.upenn.edu

Elizabeth Hood, PhD

Institute for Environmental Medicine, Perelman School of Medicine, Penn

ehood@pennmedicine.upenn.edu

Ching-Hui Huang, PhD

School of Engineering and Applied Science and Perelman School of Medicine, Penn

chinghu@seas.upenn.edu

Hans E. Huber, PhD

Adjunct Associate Professor, Department of Pharmacology, Perelman School of Medicine, University of Pennsylvania

hhuber@upenn.edu
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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

Dan Dongeun (Dan) Huh, PhD

Department of Bioengineering, University of Pennsylvania

huhd@seas.upenn.edu

I

Marc A. Ilies, PhD

School of Pharmacy, Temple University

mailies@temple.edu

J

Paul A. Janmey, PhD

School of Engineering and Applied Science and Perelman School of Medicine, Penn

janmey@mail.med.upenn.edu

K

Laurie Kilpatrick, PhD 

Department of Physiology, School of Medicine, Temple University

laurie.kilpatrick@temple.edu

Hyun (Michel) Koo

Department of Orthodontics, Penn School of Dental Medicine

koohy@dental.upenn.edu

Arun Kumar, PhD

Thomas Jefferson University

arun.kumar@jefferson.edu

L

John D. Lambris, PhD

Department of Pathology and Laboratory Medicine, Perelman School of Medicine

lambris@pennmedicine.upenn.edu

Daeyeon Lee, PhD

School of Engineering and Applied Science, Penn

daeyeon@seas.upenn.edu

Frank S. Lee, MD, PhD

Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania

franklee@mail.med.upenn.edu

Robert J. Levy, MD

Department of Pediatrics, CHOP/Perelman School of Medicine, Penn

levyr@email.chop.edu

Chunsheng Li, PhD

Department of Obstetrics and Gynecology, Perelman School of Medicine, Penn

lich@mail.med.upenn.edu

Esther Lim, MD

Nuclear Medicine Department, Philadelphia VA Medical CenterEsther Lim, MD

Esther.lim@va.gov

Joshua H. Lipschutz, MD

Biomedical Graduate Studies, Perelman School of Medicine, Penn

jhlipsch@mail.med.upenn.edu

Yaling Liu, PhD

Department of Mechanical Engineering & Mechanics, LeHigh University

yal310@lehigh.edu

Jennifer Lukes, PhD

Professor of Mechanical Engineering and Applies Mechanics, School of Engineering and Applies Sciences, University of Pennsylvania

jrlukes@seas.upenn.edu
Research Description:

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

Nicholas Lyssenko, PhD

Adjunct Assistant Professor, Perelman School of Medicine, Penn

nilys@mail.med.upenn.edu
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.

Comments:

https://www.ncbi.nlm.nih.gov/sites/myncbi/1tSYsgCCdbcAX/bibliography/48302311/public/?sort=date&direction=descending

M

Sergey Magnitsky, PhD

Department of Radiology, Perelman School of Medicine, Penn

magnitsk@mail.med.upenn.edu

Andrew Maidment, PhD, FAAPM

Associate Professor, Department of Radiology, Perelman School of Medicine, Penn

Andrew.Maidment@uphs.upenn.edu
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Research Description:

Nanoparticle imaging agents.

Andrei Maiseyeu, PhD

Case Western Reserve University, Department of Medicine, Cardiovascular Research Institute

andrei.maiseyeu@case.edu
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.

Keywords:

nanoparticles, imaging, cardiometobilic disease, atherosclerosis, lipoproteins, macrophages, drug delivery

Oscar Marcos Contreras, PharmD, PhD

Research Associate, Dept. of Systems Pharmacology and Translational Therapeutics, UPenn

oscarmar@pennmedicine.upenn.edu
Research Description:

I am working in Dr. Vladimir Muzykantov's Lab.

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:

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.

Liudmila Mazaleuskaya, PhD

Research Associate, ITMAT and Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania

mazali@mail.med.upenn.edu
Research Description:

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

Jan J. Melenhorst, PhD

Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania

mej@mail.med.upenn.edu

Michael C. Milone, MD, PhD

Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania

milone@mail.med.upenn.edu

Michael Mitchell, PhD

Skirkanich Assistant Professor of Innovation, Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania

mjmitch@seas.upenn.edu
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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.

Claire Mitchell, PhD

Professor, Department of Anatomy and Cell Biology School of Dental Medicine University of Pennsylvania

chm@upenn.edu
View Publications in MyBibliography
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

Alisa Morss Clyne, PhD

Associate Professor, Mechanical and Biomedical Engineering, Drexel University

asm67@drexel.edu
View Publications in MyBibliography
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).

Christopher Murray, PhD

School of Engineering and Applied Science, Penn

cbmurray@seas.upenn.edu

Vladimir R. Muzykantov, MD, PhD

Department of Pharmacology, Perelman School of Medicine, Penn

muzykant@pennmedicine.upenn.edu

N

Kido Nwe, PhD

School of Engineering and Applied Science and Perelman School of Medicine, Penn

kidonwe@seas.upenn.edu

P

Trevor Penning, PhD

Department of Pharmacology, Perelman School of Medicine, Penn

penning@upenn.edu

Virgil Percec, PhD

Department of Chemistry, School of Arts and Sciences, Penn

percec@sas.upenn.edu

Stephen Pickup, PhD

Small Animal Imaging Facility, Penn

pickup@upennmedicine.upenn.edu

Mortimer Poncz, MD

Department of Pediatrics, CHOP/Perelman School of Medicine, Penn

poncz@email.chop.edu

Anatoly V. Popov, PhD

Department of Radiology, Perelman School of Medicine, Penn

avpopov@mail.med.upenn.edu

Robert K. Prud'homme, PhD

School of Engineering and Applied Science, Princeton

prudhomm@princeton.edu

Daniel A. Pryma, MD

Department of Radiology, Hospital of the University of Pennsylvania

daniel.pryma@uphs.upenn.edu

R

Ravi Radhakrishnan, PhD

School of Engineering and Applied Science and Perelman School of Medicine, Penn

rradhak@seas.upenn.edu

Rahim R. Rizi, PhD

Department of Radiology, Perelman School of Medicine, Penn

Rahim.Rizi@uphs.upenn.edu

S

Janet Sawicki, PhD

Lankenau Institute for Medical Research, Thomas Jefferson University and College of Medicine, Drexel University

Sawicki@limr.org
Research Description:

Development of effective therapies for metastatic cancer, including prostate, ovaries, cervix and pancreas. Therapeutic strategies based on the delivery of genetic material, specifically DNA and siRNA, exclusively to tumor cells.

Keywords:

non-viral vectors, stem cells, ovarian cancer, HuR, dendrimers.

Hao Shen, PhD

Department of Microbiology Perelman School of Medicine University of Pennsylvania

hshen@mail.med.upenn.edu

Songtao Shi, DDS, MS, PhD

Department of Anatomy & Cell Biology, Penn Dental Medicine

songtaos@dental.upenn.edu

Wan Y. Shih, PhD

School of Biomedical Engineering, Science and Health Systems, Drexel University

wan.y.shih@drexel.edu

Wei-Heng Shih, PhD

College of Engineering, Drexel University

shihwh@drexel.edu

Vladimir Shuvaev, MD, PhD

Dr., Department of Pharmacology and Center for Translational Targeted Therapeutics and Nanomedicine of the Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania.

shuvaevv@pennmedicine.upenn.edu

Donald L. Siegel, MD, PhD

Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania

SIEGELD@PENNMEDICINE.UPENN.EDU

Steven J. Siegel, MD, PhD

Department of Psychiatry, Perelman School of Medicine, Penn

Kara Spiller, PhD

Associate Professor, Drexel University School of Biomedical Engineering, Science, and Health Systems

spiller@drexel.edu
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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

*Selected for Outstanding PhD Student Award from the Society for Biomaterials.

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. +Co-first authors. *Co-corresponding authors.

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. *Co-corresponding authors.

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. *Emerging Investigators issue

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.

*Young Innovators issue

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.

Kathleen Stebe, PhD

Deputy Dean for Research and Innovation and Goodwin Professor of Engineering and Applied Science

kstebe@seas.upenn.edu
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

Millicent O. Sullivan, PhD

College of Engineering, University of Delaware

msulliva@udel.edu

T

Drew A Torigian, MD, MA

Department of Radiology, Hospital of the University of Pennsylvania

Drew.Torigian@uphs.upenn.edu

Andrew Tsourkas, PhD

School of Engineering and Applied Science and Perelman School of Medicine, Penn

atsourk@seas.upenn.edu
Research Description:

Developing molecular imaging probes to improve the diagnostic yield of non- or minimally-invasive imaging procedures and diagnostic assays.

Keywords:

Molecular imaging, probes, contrast agents, magnetic resonance, fluorescence, bioluminescence

V

Sergei Vinogradov, PhD

Department of Biochemistry and Biophyscics, Perelman School of Medicine, Penn

VINOGRAD@PENNMEDICINE.UPENN.EDU

W

Mei-Lun Wang, MD

Department of Pediatrics, CHOP/Perelman School of Medicine, Penn

wangm@email.chop.edu

Rongsheng (Ross) Wang

Assistant Professor, Department of Chemistry, Temple University

rosswang@temple.edu
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

Miriam Wattenbarger, PhD

School of Engineering and Applied Science, Penn

mwattenb@seas.upenn.edu

David B. Weiner, PhD

Department of Pathology and Laboratory Medicine, Perelman School of Medicine, Penn

dbweiner@mail.med.upenn.edu

John W. Weisel, PhD

Department: Cell and Developmental Biology, Perelman School of Medicine, Penn

weisel@mail.med.upenn.edu

Drew Weissman, MD, PhD

Professor

dreww@pennmedicine.upenn.edu
Research Description:

nucleoside-modified mRNA in lipid nanoparticle therapeutics

Keywords:

pseudouridine, mRNA, vaccine, lipid nanoparticle

Margaret A. Wheatley, PhD

School of Biomedical Engineering, Science and Health Systems, Drexel University

wheatley@coe.drexel.edu

E. John Wherry, PhD

Professor, Richard and Barbara Schiffrin President’s Distinguished Professor; Director, Institute for Immunology; Chair, Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of Medicine

wherry@pennmedicine.upenn.edu
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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

Robert L. Wilensky, MD

Department of Medicine, Hospital of the University of Pennsylvania

rwilensk@mail.med.upenn.edu

John H. Wolfe, VMD, PhD

Professor, Department of Pathobiology, School of Veterinary Medicine, Penn and Penn and Department of Pediatrics, CHOP/Perelman School of Medicine, Penn

jhwolfe@vet.upenn.edu
Research Description:

gene and stem cell therapies for neurological diseases

Ho Lun Wong, PhD

Department of Pharmaceutical Sciences, School of Pharmacy, Temple University

ho-lun.wong@temple.edu

Y

Shu Yang

Professor, Department of Materials Science and Engineering

shuyang@seas.upenn.edu
Research Description:

Synthesis and assembly of polymer nanoparticles for controlled encapsulation and release of drugs; creating anti-fouling surfaces; synthesis of magnetic responsive nano-/microparticles and polymer composites and their actuation

Keywords:

polymer nanoparticles, drug delivery, anti-fouling, magnetic particles.

Darwin Ye, PhD candidate

Ph.D Candidate at Perelman School of Medicine Cancer Biology

darwinye@mail.med.upenn.edu

Z

Sergei V. Zaytsev, PhD

Department of Pathology and Laboratory Medicine, Penn

zaytsev@mail.med.upenn.edu

Yinghui Zhong, Ph.D.

Associate Professor, School of Biomedical Engineering, Science and Health Systems Drexel University

yz348@drexel.edu
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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.

Rong Zhou, PhD

Department of Radiology, Perelman School of Medicine, Penn

Rong.Zhou@uphs.upenn.edu