Robert Yarchoan, M.D.
Dr. Yarchoan has played a major role in developing the first successful drugs to treat HIV infection. More recently, his research is focused on the study of and development of treatment for HIV-associated malignancies, with a focus on those caused by Kaposi sarcoma-associated herpesvirus (KSHV). As Chief, Dr. Yarchoan oversees the Branch’s clinical/translational research program, which encompasses the development of novel therapies for HIV infection, the study of the viral causes of HIV-associated malignancies, and the development of novel therapies for HIV-associated malignancies.
Molecular Characterization of Viral-associated Tumors, Tumors occurring in the Setting of HIV or other Immune Disorders and Castleman DiseaseOpen - RecruitingNCI Protocol ID NCI-17-C-0174Investigator Robert Yarchoan, M.D.Share this trial: Referral Contacts
Contact Name Phone Number Matthew Lindsley, MPH, MSN, RN 240-760-6071
Phase I/II Study of Lenalidomide Combined with Modified DA-EPOCH and Rituximab (EPOCH-R2) in Primary Effusion Lymphoma or KSHV-associated Large Cell LymphomaOpen - RecruitingNCI Protocol ID NCI-16-C-0171Investigator Robert Yarchoan, M.D.Share this trial: Referral Contacts
Contact Name Phone Number Anaida Widell, RN 301-451-3694
Phase I Study of Pembrolizumab in Patients with Human Immunodeficiency Virus (HIV) and Relapsed/Refractory or Disseminated Malignant NeoplasmOpen - RecruitingNCI Protocol ID NCI-16-C-0066Investigator Robert Yarchoan, M.D.Share this trial: Referral Contacts
Contact Name Phone Number Karen Aleman 301-435-5621
A Phase 1 Trial of Pomalidomide in Combination with Liposomal Doxorubicin in Patients with Advanced or Refractory Kaposi SarcomaOpen - RecruitingNCI Protocol ID NCI-16-C-0047Investigator Robert Yarchoan, M.D.
Pilot Study of Tocilizumab in Patients with Symptomatic Kaposi Sarcoma Herpesvirus (KSHV) - associated Multicentric Castleman DiseaseOpen - RecruitingNCI Protocol ID NCI-11-C-0233Investigator Robert Yarchoan, M.D.
Natural History Study of the KSHV Inflammatory Cytokine Syndrome (KICS) Incorporating Pilot Evaluation of KSHV Targeted TherapiesOpen - RecruitingNCI Protocol ID NCI-11-C-0220Investigator Robert Yarchoan, M.D.
AIDS-Related Primary Central Nervous System Lymphoma: A Phase II Pilot Study of High-Dose Intravenous Methotrexate with Rituximab, Leucovorin Rescue and Highly Active Antiretroviral TherapyOpen - RecruitingNCI Protocol ID NCI-06-C-0051Investigator Robert Yarchoan, M.D.Share this trial: Referral Contacts
Contact Name Phone Number
Targeted Oncolytic Virotherapy and Natural History Study of KSHV-Associated Multicentric Castleman's Disease with Laboratory and Clinical Correlates of Disease ActivityOpen - RecruitingNCI Protocol ID NCI-04-C-0275Investigator Robert Yarchoan, M.D.
Collection of Blood, Bone Marrow, Tumor, or Tissue Samples from Patients with HIV Infection, KSHV Infection, Viral-related Pre-malignant Lesions, and/or CancerOpen - RecruitingNCI Protocol ID NCI-01-C-0038Investigator Robert Yarchoan, M.D.Share this trial: Referral Contacts
Contact Name Phone Number Anaida Widell 240-760-6074
The research in the Retroviral Diseases Section includes a laboratory and clinical component, and there is substantial integration and cross-fertilization between these components.
Pathogenesis of Virus-Associated Tumors
One main area of research focus is the study of the pathogenesis of viral-associated tumors, especially those associated with Kaposi's sarcoma-associated herpesvirus (KSHV), also called human herpesvirus-8 (HHV-8). KSHV is the causal agent of Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman disease (MCD). We observed that KS preferentially develops in the feet and other areas of the body with a poor vascular supply. In studying this phenomenon, we discovered that KSHV is induced by hypoxia to undergo lytic replication and to produce factors with direct or indirect angiogenic activity. In further exploring this observation, we found that the genome of KSHV encodes for several hypoxia response elements (HRE) that respond to hypoxia-induced factor (HIF). We are currently exploring the differential upregulation of various KSHV genes by hypoxia and how this may influence the pathogenesis of KSHV-induced tumors. In an extension of this work, we are also exploring the differential upregulation of various cellular genes by two different HIFs, HIF-1 and HIF-2. We are also exploring how LANA interacts with HIF in affecting KSHV and cellular genes, and other factors that can upregulate certain KSHV genes. In particular, we are exploring how spliced X-box protein (XBP) can directly upregulate KSHV viral interleukin-6 (vIL-6); this may play an important role in the pathogenesis of MCD. In addition, we are exploring how KSHV latency-associated nuclear antigen (LANA) is affected by oxidative stress, and in particular its cleavage by cellular caspases.
We are also studying the pathogenesis of KSHV-associated MCD and related disorders. As part of of this effort, we are studying the cytokine dysregulation in MCD and its association with symptomatology. We have also recently identified a new MCD-like syndrome caused by KSHV in which patients have inflammatory symptoms similar to those of MCD, have increase KSHV viral IL-6 levels, but do not have pathological findings of MCD. This syndrome, which we are calling KSHV-associated inflammatory cytokine syndrome (KICS), may account for otherwise unexplained fevers in certain patients with HIV and KSHV co-infection.
Development of Novel Therapies for AIDS-Related Malignancies and HIV Infection
Another main focus of our research is the development of novel therapies for HIV-related malignancies and HIV infection. This work is informed by the pathogenesis-associated work described above. One area of principal interest is Kaposi's sarcoma (KS). Our group is exploring approaches that are based on an understanding of the pathogenesis of this disease but that do not involve the use of cytotoxic chemotherapy. There is evidence that production of virally encoded and cellular angiogenesis-inducing factors by KSHV-infected cells is important in the pathogenesis of KS, and this makes antiangiogenesis approaches attractive to consider. Our group recently showed that bevacizumab (humanized anti-VEGF antibody) has activity in KS, and we are now studying the combination of this with liposomal doxorubicin and also pomalidomide, an analog of thalidomide. We recently initiated protocols to explore targeted therapy for KSHV-MCD and HIV-associated primary central nervous system lymphoma.
Selected Recent Publications
RNA sequencing reveals that Kaposi sarcoma-associated herpesvirus infection mimics hypoxia gene expression signature.PLoS Pathogens. in press, 2017. [ Journal Article ]
Pomalidomide for Symptomatic Kaposi's Sarcoma in People With and Without HIV Infection: A Phase I/II Study.J Clin Oncol. 34(34): 4125-4131, 2016. [ Journal Article ]
Identification of Caspase Cleavage Sites in KSHV Latency-Associated Nuclear Antigen and Their Effects on Caspase-Related Host Defense Responses..PLoS Pathog. . 11(7): e1005064, 2015. [ Journal Article ]
Clinical Features and Outcomes of Patients With Symptomatic Kaposi Sarcoma Herpesvirus (KSHV)-associated Inflammation: Prospective Characterization of KSHV Inflammatory Cytokine Syndrome (KICS).Clin Infect Dis. 62(6): 730-8, 2016. [ Journal Article ]
Induction of Kaposi's Sarcoma-Associated Herpesvirus-Encoded Viral Interleukin-6 by X-Box Binding Protein 1.J Virol. 90(1): 368-78, 2015. [ Journal Article ]
Dr. Robert Yarchoan received his B.A. from Amherst College with a major in biophysics and his M.D. from the University of Pennsylvania. He trained in internal medicine at the University of Minnesota and Immunology in the Metabolism Branch, NCI. He then joined the laboratory of Dr. Samuel Broder, where he played a major role in the development of the first effective therapies for HIV infection, including zidovudine (AZT), didanosine (ddI), and zalcitabine (ddC). In particular, he led the first clinical trials of these drugs, was a co-inventor of didanosine and zalcitabine as AIDS therapies, and led initial studies of combination anti-HIV therapy. He was a Section Chief in the Medicine Branch from 1991 to 1996 and was named chief of the newly formed HIV and AIDS Malignancy Branch in 1996. Since that time, he has focused much of his research on AIDS-related malignancies, especially tumors caused by Kaposi's sarcoma-associated herpesvirus (KSHV).
Among other honors, he has been awarded the Assistant Secretary for Health Award and the U.S. Public Health Service Outstanding Service Medal, has been inducted as a Fellow of the American Association for the Advancement of Science (AAAS), and is a member of the American Society for Clinical Investigation. In December, 2006, he was a recipient of the first NIH World AIDS Day Award, and in November, 2007, he received the NCI HIV/AIDS Research Excellence Award along with Drs. Samuel Broder, Robert C. Gallo, and Hiroaki Mitsuya. Recent honors and awards include: 2013, an honorary degree (Doctor of Science) from Amherst College; 2014, the Abbott Award in Clinical and Diagnostic Immunology by the American Society for Microbiology; 2016, elected into the Association of American Physicians; 2017, elected into the American Academy of Microbiology.
In December 2007, Dr. Yarchoan also was appointed as the first Director of the NCI Office of HIV and AIDS Malignancy (OHAM). This office, which is in the Office of the Director, NCI, coordinates and prioritizes the HIV/AIDS and AIDS malignancy research portfolio throughout the NCI.
|Hong Seok Choi Ph.D.||Postdoctoral Fellow (Visiting)|
|David A. Davis, Ph.D.||Staff Scientist|
|Matthew Lindsley R.N.||Research Nurse|
|Kathryn Lurain M.D., M.P.H.||Clinical Fellow|
|Ramya Ramaswami M.D.||Clinical Fellow|
|Prabha Shrestha Ph.D.||Postdoctoral Fellow (Visiting)|
|Alexandra Stream||Postbaccalaureate Fellow|
|Victoria Wang M.D.||Research Biologist|
|Yi-Quan Wu Ph.D.||Postdoctoral Fellow (Visiting)|