PROGRAMS and SERVICES
For further information, applicants should contact:
Dr. Robert Yarchoan
Robert Yarchoan, MD
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. Basic laboratory research focuses on HIV and Kaposi sarcoma herpesvirus (KSHV) biology, the pathogenesis of KSHV-associated malignancies, and cellular responses to hypoxia and other stress. Clinical studies are aimed at understanding the biology and natural history of virally associated malignancies and developing novel therapies for AIDS-related malignancies through early phase clinical studies.
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 and/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 and conditions, including Kaposi's sarcoma , multicentric Castleman's disease, primary effusion lymphoma, and KSHV-associated inflammatory cytokine syndrome (KICS); studies of certain AIDS-related lymphomas; and other HIV-associated tumors (e.g. anal cancer). 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; development of novel anti-HIV drugs; HIV resistance; the role of KSHV in the pathogenesis of Kaposi's sarcoma and other KSHV-associated tumors; the role of KSHV microRNA in disease pathogenesis; effects of cellular stress (e.g. hypoxia) on cellular and viral gene activation.
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. Physicians interested in participating in clinical research in the branch will generally have ACGME Accredited Board Certification in either Pediatrics or Internal Medicine plus relevant subspecialty training (usually, but not limited to, Oncology and/or Hematology). Additionally, candidates who are eligible for a J1 ECFMG sponsored visa and who have a strong academic background and demonstrated commitment to the field of Hematology and/or Oncology in the setting of HIV/AIDS will be considered.
Applicants interested in both qualifying for subspecialty certification in Medical Oncology and in obtaining research training in AIDS or AIDS malignancies or AIDS are encouraged to 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 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 novel therapy for Kaposi's sarcoma, a study of the mechanisms by which KSHV causes Kaposi's sarcoma and other diseases, interaction between KSHV and cellular factors, and studies of HIV protease. Along with Drs. Hiroaki Mitsuya and Samuel Broder, Dr. Yarchoan 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.
- 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.
- Mark Polizzotto, M.B., B.S., B.Med.Sc. - An Associate Clinical Investigator is studying polalidomide as a novel therapy for Kaposi sarcoma, KSHV-associated multicentric Castkleman's disease, and a newly defined syndrome, KSHV-associated inflammatory cytokine syndrome (KICS).
- Members of the Branch have long-standing collaborations with investigators including Giovanna Tosato, Denise Whitby, Wyndham Wilson, Frank Maldarelli, 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, 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.
- Abend JR, Uldrick T, Ziegelbauer JM. Regulation of tumor necrosis factor-like weak inducer of apoptosis receptor protein (TWEAKR) expression by Kaposi's sarcoma-associated herpesvirus microRNA prevents TWEAK-induced apoptosis and inflammatory cytokine expression. J Virol. 2010 Dec;84(23):12139-51.
- 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.
- Wang V, Davis DA, Veeranna RP, Haque M and Yarchoan R. Characterization of the activation of protein tyrosine phosphatase, receptor-type Z polypeptide 1(PTPRZ1) by hypoxia inducible factor-2 alpha. PLoS One. 2010 Mar;5(3):e9641.
- Burbelo PD, Issa AT, Ching KH, Wyvill KM, Little RF, Iadarola MJ, Kovacs JA, Yarchoan R. Distinct profiles of antibodies to Kaposi sarcoma-associated Herpesvirus antigens in patients with Kaposi sarcoma, Multicentric Castleman disease, and primary effusion lymphoma. J Infect Dis. 2010 June;201(12):1919-22.
- Uldrick TS, Wang V, O'Mahony D, Aleman K, Wyvill KM, Marshall V, Steinberg SM, Pittaluga S, Maric I, Whitby D, Tosato G, Little RF, Yarchoan R. An IL-6-related systemic inflammatory syndrome in patients co-infected with Kaposi sarcoma-associated herpesvirus and HIV but without multicentric Castleman disease. Clin Inf Dis. 2010 Aug;51(3):350-8.
- Uldrick TS, Polizzotto MN, O'Mahony D, Aleman K, Wyvill KM, Wang V, Marshall V, Pittaluga S, Steinberg SM, Tosato G, Whitby D, Little RF, Yarchoan R. High-dose zidovudine in combination with valgancyclovir in the treatment of symptomatic Kaposi sarcoma-associated herpesvirus-associated multicentric Castleman disease: A pilot study of virus-activated cytotoxic therapy. Blood. 2011 Jun 30;117(26):6977-86.
- Yarchoan R, Uldrick TS, Little RF. AIDS-related malignancies. In: DeVita VT Jr., Lawrence TS, and Rosenberg SA, Eds., Cancer: Principles and Practice of Oncology, 9th Edition. Lippincott Williams and Wilkins, Philadelphia. 2011; 2099-2112.
- Veeranna RP, Haque M, Davis DA, Yamg M, and Yarchoan R. Kaposi's sarcoma-associated Herpesvirus latency-associated nuclear antigen induction by hypoxia and hypoxia-inducable factors. J Virol. 2012 Jan;86(2):1097-108.
- Polizzotto MN, Uldrick TS, Hu D, and Yarchoan R. Clinical Manifestations of Kaposi sarcoma herpesvirus lytic activation: multicentric Castleman disease (KSHV-MCD) and the KSHV inflammatory cytokine syndrome. Front Microbiol. 2012;3:73.
- Uldrick TS, Wyvill KM, Kumar P, O'Mahony D, Bernstein W, Aleman K, Polizzotto MN, Steinberg SM, Pittaluga S, Marshall V, Whitby D, Little RF, and Yarchoan R. A Phase II Study of Bevacizumab in Patients with Human Immunodeficiency Virus-associated Kaposi Sarcoma on Antiretroviral Therapy. J Clin Oncol. 2012 May 1;30(13):1476-83.
- Davis DA, Soule EE, Davidoff KS, Daniels SI, Naiman ME, and Yarchoan R. Activity of human immunodeficiency virus type 1 protease inhibitors against the initial autocleavage in Gag-Pol polyprotein processing. Antimicrob Agents Chemother. 2012 Jul;56(7):3620-8.
- Uldrick TS, Polizzotto MN, and Yarchoan R. Recent Advances in Kaposi Sarcoma Herpesvirus (KSHV)-Associated Multicentric Castleman Disease. Curr Opin Oncol. 2012 Sep;24(5):495-505.
- Abend JR, Ramalingam D, Kieffer-Kwon P, Uldrick TS, Yarchoan R, and Ziegelbauer JM. KSHV microRNAs target two components of the TLR/IL-1R signaling cascade, IRAK1 and MYD88, to reduce inflammatory cytokine expression. J Virol. 2012 Nov;82(21):1163-74.
- Venkataraman G, Uldrick TS, Aleman K, O'Mahony D, Karcher DS, Steinberg SM, Raffeld MA, Marshall V, Whitby D, Little RF, Yarchoan R, Pittaluga S, and Maric I. Bone marrow findings in HIV positive patients with Kaposi sarcoma Herpesvirus-associated Multicentric Castleman disease. Am J Clin Pathol. 2013 May;139(5):651-61.
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