Michael C. Milone

faculty photo
Assistant Professor of Pathology and Laboratory Medicine at the Hospital of the University of Pennsylvania
Staff Physician, Department of Pathology and Laboratory Medicine
Department: Pathology and Laboratory Medicine

Contact information
3400 Spruce Street 7103 Founders Pavilion
Philadelphia, PA 19104
Office: 215-662-6575
Fax: 215-662-7529
Graduate Group Affiliations
Education:
B.S (Chemical Biology)
Stevens Institute of Technology, 1993.
Ph.D (Experimental Pathology/ Immunology)
UMDNJ - Graduate School of Biomedical Sciences, 1999.
M.D. (Medical Doctor)
UMDNJ- New Jersey Medical School, 1999.
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Description of Research Expertise

Research in my laboratory aims toward improving cancer and transplantation therapy through the development of new immunotherapeutic modalities. Active research projects in my laboratory include:

1) Developing improved chimeric antigen receptors (CARs) for adoptive immunotherapy of cancer.

These projects are focused upon understanding the mechanisms of signal transduction of artificial chimeric antigen receptors through traditional biochemical studies along with high resolution dynamic imaging of artificial and natural T cell receptors. New CAR designs are also under development to permit more controlled activation of T cells.

2) Developing novel T cell stimulatory substrates based upon nano- and micro-fabricated surfaces for control of T cell proliferation and differentiation.

This project is part of a collaborative effort supported by the NIH Common Fund. Details of this project can be found at the center's website (www.mechanicalbiology.org) or the NIH common fund site (http://commonfund.nih.gov/nanomedicine/devcenters/mechanicalbiology.asp)

Description of Itmat Expertise

My laboratory is focused upon developing methods to use the immune system to treat cancer. Active research includes 1) exploring the mechanical properties of artificial adhesion substrates used in T cell culture and their influence on T cell biology, 2) development of artificial antigen receptors and signaling systems for control of T cell specificity

Selected Publications

Vijay G. Bhoj, Dimitrios Arhontoulis, Gerald Wertheim, James Capobianchi, Colleen A. Callahan, Christoph T. Ellebrecht, Amrom E. Obstfeld, Simon F. Lacey, Jan J. Melenhorst, Farzana Nazimuddin, Wei-Ting Hwang, Shannon L. Maude, Mariusz A. Wasik, Adam Bagg, Stephen Schuster, Michael D. Feldman, David L. Porter, Stephen A. Grupp, Carl H. June, and Michael C. Milone: Persistence of long-lived plasma cells and humoral immunity in individuals responding to CD19-directed CAR T cell therapy. Blood In press, May 2016.

Hu Junqiang, Gondarenko Alexander A, Dang Alex P, Bashour Keenan T, O'Connor Roddy S, Lee Sunwoo, Liapis Anastasia, Ghassemi Saba, Milone Michael C, Sheetz Michael P, Dustin Michael L, Kam Lance C, Hone James C: High-Throughput Mechanobiology Screening Platform Using Micro- and Nanotopography. Nano letters In Press, Mar 2016.

Kawalekar Omkar U, O'Connor Roddy S, Fraietta Joseph A, Guo Lili, McGettigan Shannon E, Posey Avery D, Patel Prachi R, Guedan Sonia, Scholler John, Keith Brian, Snyder Nathaniel, Blair Ian, Milone Michael C, June Carl H: Distinct Signaling of Coreceptors Regulates Specific Metabolism Pathways and Impacts Memory Development in CAR T Cells. Immunity 44(2): 380-90, Feb 2016.

Ruella Marco, Kenderian Saad S, Shestova Olga, Fraietta Joseph A, Qayyum Sohail, Zhang Qian, Maus Marcela V, Liu Xiaobin, Nunez-Cruz Selene, Klichinsky Michael, Kawalekar Omkar U, Lacey Simon F, Milone Michael, Mato Anthony R, Schuster Stephen J, Kalos Michael, June Carl H, Gill Saar, Wasik Mariusz A: The Addition of the BTK inhibitor Ibrutinib to Anti-CD19 Chimeric Antigen Receptor T Cells (CART19) Improves Responses against Mantle Cell Lymphoma. Clin Cancer Res Jan 2016 Notes: Epub ahead of print.

Porter DL, Hwang W-T, Frey NV, Lacey SF, Shaw PA, Loren AW, Bagg A, Marcucci KT, Shen A, Gonzalez V, Ambrose D, Grupp SA, Chew A, Zheng Z, Milone MC, Levine BL, Melenhorst JJ, June CH: Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia. Sci Transl Med 7(303): 303ra139, Sep 2015 Notes: doi: 10.1126/scitranslmed.aac5415.

Wang E, Wang L-C, Tsai C-Y, Bhoj V, Gershenson Z, Moon E, Newick K, Sun J, Lo A, Baradet T, Feldman MD, Barrett D, Puré E, Albelda S, Milone MC.: Generation of Potent T-cell Immunotherapy for Cancer Using DAP12-Based, Multichain, Chimeric Immunoreceptors. Cancer Immunology Research. 3(7): 815-26, Jul 2015.

Xiang Y, Stine ZE, Xia J, Lu Y, O'Connor RS, Altman BJ, Hsieh AL, Gouw AM, Thomas AG, Gao P, Sun L, Song L, Yan B, Slusher BS, Zhuo J, Ooi LL, Lee CGL, Mancuso A, McCallion AS, Le A, Milone MC, Rayport S, Felsher DW, Dang CV: Targeted inhibition of tumor-specific glutaminase diminishes cell-autonomous tumorigenesis. J Clin Invest 125(6): 2293-306, Apr 2015 Notes: doi: 10.1172/JCI75836. Epub 2015 Apr 27.

Frigault MJ, Lee J, Basil MC, Carpenito C, Motohashi S, Scholler J, Kawalekar OU, Guedan S, McGettigan SE, Posey AD, Ang S, Cooper LJN, Platt JM, Johnson FB, Paulos CM, Zhao Y, Kalos M, Milone MC, June CH: Identification of Chimeric Antigen Receptors That Mediate Constitutive or Inducible Proliferation of T Cells. Cancer Immunol Res 3(4): 356-67, Jan 2015.

Moon EK, Wang L-C, Dolfi DV, Wilson CB, Ranganathan R, Sun J, Kapoor V, Scholler J, Puré E, Milone MC, June CH, Riley JL, Wherry EJ, Albelda SM.: Multifactorial T-cell Hypofunction That Is Reversible Can Limit the Efficacy of Chimeric Antigen Receptor-Transduced Human T cells in Solid Tumors. Clin Cancer Res 20(16): 4262-73, Aug 2014.

Bashour KT, Tsai J, Shen K, Lee J-H, Sun E, Milone MC, Dustin ML, Kam LC: Cross talk between CD3 and CD28 is spatially modulated by protein lateral mobility. Mol Cell Biol 34(6): 955-64, Mar 2014 Notes: doi: 10.1128/MCB.00842-13. Epub 2013 Dec 30.

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Last updated: 05/10/2016
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