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)
Saha Asim, O'Connor Roddy S, Thangavelu Govindarajan, Lovitch Scott B, Dandamudi Durga Bhavani, Wilson Caleph B, Vincent Benjamin G, Tkachev Victor, Pawlicki Jan M, Furlan Scott N, Kean Leslie S, Aoyama Kazutoshi, Taylor Patricia A, Panoskaltsis-Mortari Angela, Foncea Rocio, Ranganathan Parvathi, Devine Steven M, Burrill Joel S, Guo Lili, Sacristan Catarina, Snyder Nathaniel W, Blair Ian A, Milone Michael C, Dustin Michael L, Riley James L, Bernlohr David A, Murphy William J, Fife Brian T, Munn David H, Mil: Programmed death ligand-1 expression on donor T cells drives graft-versus-host disease lethality. The Journal of clinical investigation 126 (7): 2642-60,2016.
Ellebrecht CT, Bhoj VG, Nace A, Choi EJ, Mao X, Cho MJ, Di Zenzo G, Lanzavecchia A, Seykora JT, Cotsarelis G, Milone MC*, Payne AS*.: Reengineering chimeric antigen receptor T cells for targeted therapy of autoimmune disease Science In press : 2016.
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 : 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 (4): 2198-204,2016.
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): 380-90,2016.
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 : 2016.
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): 303ra139,2015.
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): 815-26,2015.
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): 2293-306,2015.
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): 356-67,2015.