Graduate Medical Education (GME): HIV and AIDS Malignancy Research
National Institutes of Health - Baltimore, MD

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Graduate Medical Education (GME): HIV and AIDS Malignancy Research

Robert Yarchoan, MD

Overview
The HIV and AIDS Malignancy Branch (HAMB) in the Center for Cancer Research of the National Cancer Institute (NCI) conducts translational research on AIDS-related malignancies and HIV infection. Investigators engage in basic laboratory research, preclinical studies, and clinical trials. The clinical trials are aimed at developing novel therapies for AIDS-related malignancies and HIV infection and on understanding the effects of therapies on disease pathogenesis.

Structure of the Clinical Training Program
The program is designed for physicians who have completed their specialty training in Internal Medicine (or Pediatrics) as well as their initial subspecialty clinical training in Oncology or Hematology, and who are interested in obtaining additional translational or clinical training in AIDS malignancies. Physicians in HAMB may choose to learn how to conduct high-quality, translational clinical studies. Current areas of focus in clinical research include: novel therapies for KSHV-related tumors, including Kaposi’s sarcoma and multicentric Castleman’s disease; studies of certain AIDS-related lymphomas; and novel approaches to anti-HIV therapy. Clinical trials involving patients with HIV-related lymphomas are currently being conducted in collaboration with other NCI investigators. Physicians in HAMB may also choose to participate in basic laboratory research. Areas of laboratory research interest in the Branch at present include studies of: the biochemistry of HIV protease; HIV resistance; the regulation of splicing in human papilloma virus and Kaposi's sarcoma-associated herpesvirus (KSHV); the role of KSHV in the pathogenesis of Kaposi's sarcoma and other KSHV-associated tumors; and the role of KSHV microRNA in disease pathogenesis.

Patients are evaluated and treated at the NIH Clinical Center, a 240 bed state-of–the-art research hospital on campus, that provides a stimulating environment in which to learn the principles and practice of translational research. Many significant advances in AIDS and AIDS malignancy research have been made at the NIH through the collaborative efforts and shared resources of the NCI and the Clinical Center. There are numerous research seminars and lectures given on a daily basis throughout the NIH and open to the NIH community. Formal course work in the basic sciences is available through the NIH Foundation for the Advancement of Education of the Sciences.

Eligibility and Application Process
Applicants interested in obtaining clinical or translational training in HIV-associated cancers may apply directly to the HIV and AIDS Malignancy Branch. It is anticipated that most physicians interested in participating in clinical research in the branch will have ACGME Accredited Board Certification in either Pediatrics or Internal Medicine plus relevant subspecialty training (usually, but not limited to, Oncology or Hematology). While this is not an absolute requirement, exceptions will be made only for candidates who have a strong academic background in relevant areas. Finally, physicians with a strong laboratory research background but without the above credentials may apply to individual laboratories in HAMB for training in laboratory research.

Applicants interested in both qualifying for subspecialty certification in Medical or Pediatric Oncology and in obtaining research training in AIDS or AIDS malignancies or AIDS may apply to those relevant programs in the National Cancer Institute. As noted in the descriptions of those programs, the Fellows have the option of spending their second and third years in various laboratories and branches of the National Cancer Institute, including the HAMB.

NIH Loan Repayment Program
Physicians doing AIDS research in HAMB may be eligible for participation in the NIH Loan Repayment Program for AIDS Research .

Program Faculty and Research Interests

Robert Yarchoan, M.D. Research interests include development of therapy for Kaposi's sarcoma using anti-angiogenesis and other approaches, a study of the mechanisms by which KSHV causes Kaposi's sarcoma and other diseases, immunologic/vaccination approaches to the therapy of HIV infection, and studies of HIV protease. Along with Drs. Hiroaki Mitsuya and Samuel Broder, developed some of the initial anti-HIV drugs including didanosine and zalcitabine.

Thomas Uldrick, M.D. A staff physician conducting clinical research in HIV-associated malignancies. Research interests include multicentric Castleman’s disease, Kaposi’s sarcoma, HIV-associated lymphoma, and other HIV-associated malignancies.

Hiroaki Mitsuya, M.D., Ph.D. An immunologist and virologist who, along with Drs. Yarchoan and Samuel Broder, developed some of the early anti-HIV drugs and has a continued interest in drug resistance to HIv drugs and developing novel therapies.

Zhi-Ming Zheng, M.D., Ph.D. A virologist with research interests focusing on the regulation of splicing in human papilloma virus and KSHV.

Joseph Ziegelbauer, Ph.D. A molecular virologist interested in studying KSHV-encoded microRNAs and their interaction with host genes. The goal is to understand the role of these microRNAs in the viral life-cycle and in disease pathogenesis.

Members of the Branch have long-standing collaborations with Giovanna Tosato, Denise Whitby, Wyndham Wilson, and Stefania Pitaluga in the National Cancer Institute.

Examples of Papers and Chapters Authored by Program Faculty

Yarchoan, R. Clinical Implications of Basic Research: Key role for a viral lytic gene in Kaposi’s sarcoma. New Engl J. Med., 2006; 355(13): 1383-1385.

Davis DA, Singer KE, Reynolds IP, Haque M, Yarchoan R. Hypoxia enhances the phosphorylation and cytotoxicity of ganciclovir and zidovudine in KSHV-infected cells. Cancer Research. 2007; 67(14): 7003-10.

Koh Y, Matsumi S, Das D, Amano M, Davis DA, Li J, Laschenko S, Baldridge A, Shioda T, Yarchoan R, Ghosh AK, Mitsuya H. Potent inhibition of HIV-1 replication by novel non-peptidyl small molecule inhibitors of protease dimerization. J. Biol. Chem. 2007; 282(39): 28709-28720.

Little RF, Pittaluga S, Yarchoan R. Non-Hodgkin lymphoma. In: Dolin R, Masur H, Saag MS, Eds. AIDS Therapy, 3rd Edition. Churchill Livingstone/Elsevier, Philadelphia. 2007; 1031-1050.

Vogel A, Chernomordik VV, Riley JD, Hasssan M, Amyot F, Dasgeb B, Demos SG, Pursley R, Little R, Yarchoan R, Tao Y, Gandijbakhche AH. Using noninvasive multispectral tissue imaging to quantitatively assess tissue vasculature. J. of Biomedical Optics 2007;12(5): 051604-17.

Little RF, Aleman K, Kumar P, Wyvill KM, Pluda JM, Read-Connole E, Wang V, Pittaluga S, Catanzaro AT, Steinberg SM, Yarchoan R. Phase II study of pegylated liposomal doxorubicin in combination with interleukin-12 for Kaposi’s sarcoma. Blood. 2007; 110(13), 4165-71.

Yarchoan R, Little RF. AIDS-related malignancies. In: DeVita VT Jr., Lawrence TS, and Rosenberg SA, Eds., Cancer: Principles and Practice of Oncology, 8th Edition. Lippincott Williams and Wilkins, Philadelphia. 2008; 2401-17.

Morrow M, Valentin A, Little R, Yarchoan R, Pavlakis GN. A splenic marginal zone-like peripheral blood CD27+ B220- population is preferentially depleted in HIV-1 infected individuals. AIDS Research and Human Retroviruses. 2008; 24(4): 621-33.

O’Mahony D, Gandjbakhche AH, Hassan M, Vogel A, Yarchoan R. Imaging techniques for Kaposi sarcoma (KS). Journal of HIV Therapy. 2008; 13(3): 65-71. [Also published in: Pantanowitz L, Stebbing J, and Dezube B, Eds. Kaposi sarcoma. A Model of Oncogenesis. Research Signpost, Kerela, India. 2009]

Davis DA, Tebbs IR, Daniels SI, Stahl SJ, Kaufman JD, Wingfield P, Bowman MJ, Chmielewski J, Yarchoan R. Analysis and characterization of dimerization inhibition of a multi-drug resistant human immunodeficiency virus type 1 protease using a novel size exclusion chromatographic assay. Biochemical Journal. 2009; 419(2): 497-506.

Yarchoan R, Pauza CD. Cancers and HIV infection: An evolving story. In: From Cause to Care. Commemorating 25 Years of HIV/AIDS Research. American Association for the Advancement of Science, 2009; 38-40.

Housri N, Yarchoan R, Kaushal A. Radiotherapy for HIV patients: Are special precautions necessary? Cancer. In press.

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