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Carl H. June

Professor of Pathology and Laboratory Medicine
Department: Pathology and Laboratory Medicine
Graduate Group Affiliations

Contact information
554 BRB II/III
421 Curie Blvd.
Philadelphia, PA 19104
Office: (215) 573-5745
Fax: (215) 573-8590
Education
B.S. (Biology)
United States Naval Academy , 1971.
M.D.
Baylor College of Medicine, 1979.
Post-Graduate Training
Residency: Internal Medicine , National Naval Medical Center, Bethesda, Maryland, 1980-1982.
Internship: Basic Medicine , National Naval Medical Center, Bethesda, Maryland , 1979-1980.
Chief Resident: Internal Medicine , National Naval Medical Center, Bethesda, Maryland, 1982-1983.
Research Fellow , World Health Organization Immunology Research and Training Center, Geneva, Switzerland, 1978-1979.
Fellow in Oncology , University of Washington and Fred Hutchinson Cancer Research Center, Seattle, Washington, 1983-1985.
Certifications
American Board of Internal Medicine, 1982.
American Board of Internal Medicine Subspecialty of Oncology, 1985.
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Description of Research Expertise

Research Interests
human T cell biology: mechanisms of lymphocyte costimulation.

Key words: T cells, human, gene therapy, genetic engineering, signal transduction.

Description of Research
There are two themes in the laboratory. One project involves determining mechanisms of lymphocyte activation. A more recent focus is to develop and test novel forms of immunotherapy for cancer and chronic infections. In the area of T cell signal transduction, for the past ten years these studies have been focused on CD28 and CTLA-4. More recently we have also been studying mechanisms that regulate chemokine receptor expression and signal transduction in T cells. In addition, we are studying the role of telomerase expression in telomere maintenance and replicative senescence in T cells. Novel lentiviral expression systems are permitting mechanistic studies of T cell costimulation in primary T cells for the first time.

Over the last five years my laboratory has been studying the potential use of adoptive immunotherapy for cancer and HIV infection. We have developed a large-scale tissue culture technique that permits the efficient propagation of polyclonal HIV CD4 and CD8 T cell subsets. Several clinical trials involving adoptive immunotherapy of autologous and allogeneic T cells are in process. Two trials are using genetically engineered T cells.

Rotation Projects for 2006-2007
1. mechanisms of T cell costimulation, studies using shRNA and lentiviral vectors
2. lentiviral vectors to create redirected regulatory T cells
3. mechanisms of superagonist T cell and NK cell signal transduction

Lab personnel:
Elena Perez, MD, PhD, Post Doc
Michael Milone, MD, PhD, Post Doc
Nicole Aqui, MD, Post Doc
Carmine Carpenito, MD, Post Doc
Megan Suhoski, graduate student

Selected Publications

Golovina TN, Mikheeva T, Suhoski MM, Aqui NA, Tai VC, Shan X, Liu R, Balcarcel RR, Fisher N, Levine BL, Carroll RG, Warner N, Blazar BR, June CH, Riley JL.: CD28 costimulation is essential for human T regulatory expansion and function. J Immunol. 181 (4): 2855-68, Aug. 2008.

Suhoski MM, Perez EE, Heltzer ML, Laney A, Shaffer LG, Saitta S, Nachman S, Spinner NB, June CH, Orange JS.: Monosomy 1p36 uncovers a role for OX40 in survival of activated CD4+ T cells. Clin Immunol. 128: 181-9, Aug. 2008.

Perez EE, Wang J, Miller JC, Jouvenot Y, Kim KA, Liu O, Wang N, Lee G, Bartsevich VV, Lee YL, Guschin DY, Rupniewski I, Waite AJ, Carpenito C, Carroll RG, Orange JS, Urnov FD, Rebar EJ, Ando D, Gregory PD, Riley JL, Holmes MC, June CH.: Establishment of HIV-1 resistance in CD4+ T cells by genome editing using zinc-finger nucleases. Nat Biotechnol. 7: 808-16, Jul. 26 2008.

Hippen KL, Harker-Murray P, Porter SB, Merkel SC, Londer A, Taylor DK, Bina M, Panoskaltsis-Mortari A, Rubinstein P, Van Rooijen N, Golovina TN, Suhoski MM, Miller JS, Wagner JE, June CH, Riley JL, Blazar BR.: Umbilical cord blood regulatory T cell (Treg) expansion and functional effects of tumor necrosis factor receptor (TNFR) family members OX40 and 4-1BB expressed on artificial antigen-presenting Cells (aAPCs). Blood Epub, Jul. 2008.

Wallace A, Kapoor V, Sun J, Mrass P, Weninger W, Heitjan DF, June C, Kaiser LR, Ling LE, Albelda SM.: Transforming growth factor-beta receptor blockade augments the effectiveness of adoptive T-cell therapy of established solid cancer. Clin Cancer Res. 14 (12): 3966-74, Jun 2008.

Basu, Samik. Golovina, Tatiana. Mikheeva, Tatiana. June, Carl H. Riley, James L.: Cutting edge: Foxp3-mediated induction of pim 2 allows human T regulatory cells to preferentially expand in rapamycin. Journal of Immunology 180(9): 5794-8, May 1 2008.

Huang, Xin. Guo, Hongfeng. Kang, Johnthomas. Choi, Suet. Zhou, Tom C. Tammana, Syam. Lees, Christopher J. Li, Zhong-Ze. Milone, Michael. Levine, Bruce L. Tolar, Jakub. June, Carl H. Scott McIvor, R. Wagner, John E. Blazar, Bruce R. Zhou, Xianzheng.: Sleeping Beauty transposon-mediated engineering of human primary T cells for therapy of CD19+ lymphoid malignancies. Molecular Therapy: the Journal of the American Society of Gene Therapy 16(3): 580-9, Mar 2008.

Chu, Christina S. Kim, Sarah H. June, Carl H. Coukos, George.: Immunotherapy opportunities in ovarian cancer. [Review] [184 refs] Expert Review of Anticancer Therapy 8(2): 243-57, Feb 2008.

Lotze MT, Mapara MY, June CH.: Tumor immunology and immunotherapy. In Clinical Immunology: principles and practice. R.R. Rich, Fleisher, T.A., Shearer, W., Schroeder H.W., Frew A.J., and Weyand C.M. (eds.). Mosby/Elsevier, Page: 1181-1198, 2008.

Plesa, Gabriela. Dai, Jihong. Baytop, Cliff. Riley, James L. June, Carl H. O'Doherty, Una.: Addition of deoxynucleosides enhances human immunodeficiency virus type 1 integration and 2LTR formation in resting CD4+ T cells. Journal of Virology 81(24): 13938-42, Dec 2007.

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Last updated: 08/12/2008
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