This interview is with Immunology and Immunogenetics Insights editorial board member Dr Robert Yarchoan. Immunology and Immunogenetics Insights is an open access journal published by Libertas Academica.

Editor in Chief Dr Darren Flower has recently issued a call for papers.

What is the primary focus of your research?

A main focus of my work is translational research in HIV-associated tumors, especially those caused by Kaposi's sarcoma-associated herpesvirus (KSHV), also called human herpesvirus-8 (HHV-8). In the laboratory, we are exploring the physiologic factors that activate KSHV to lytic replication and ways to use this to target KSHV tumor cells, and in the clinic, we are exploring novel treatments for Kaposi's sarcoma (KS) and KSHV-induced multicentric Castleman's disease (MCD). My laboratory is also studying the protease of HIV and in particular, the factors affecting dimerization of this enzyme and ways to modulate this.

What are the most exciting developments arising from current research in your area?

We have found that hypoxia incudes lytic replication of KSHV and in addition, specifically activates certain KSHV genes such as open reading frame (ORF) 34. Furthermore, we have found that lytic KSHV genes can activate azidothymidine (AZT, zidovudine) and ganciclovir to moieties that are toxic to human cells, potentially specifically targeting KSHV-infected tumor cells. We are exploring the use of this approach to treat KSHV-MCD, a tumor in which the main clinical profile results from production of a viral IL-6 encoded by KSHV.

Who are your main collaborators? Please describe your work with them.

Some of the collaborators we are working with include Drs. Denise Whitby and Giovanna Tosato (National Cancer Institute) on KSHV virology, Hiroaki Mitsuya (National Cancer Institute) on HIV protease, and Amir Gandjbakhche (National Institute of Child health and Human Development) on novel imaging techniques of KS.

How did you come to be working in your research area?

My career has evolved over the years from studying the interactions between viruses and the immune system (focusing on influenza virus and Epstein Barr virus), to work on developing early therapies for AIDS - including codevelopment of AZT, didanosine (ddI), and other early drugs - to studying AIDS-related malignancies. The finding that KSHV is activated by hypoxia was inspired by the clinical observation that KS preferentially affects the feet, and area of the body with low tissue oxygen.

What do you think about the development of open access publishing? Have you published in an open access journal? What motivated you to do so?

This development in exchange of scientific information was championed by Dr. Harold Varmus, the previous NIH Director. It will be interesting to see how the publishing landscape evolves over the next decade.

What articles and/or books have you published recently?

Selected recent articles and chapters are as follows:

1. 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.

2. 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.

3. Yarchoan R, Pluda JM, Wyvill KM, Aleman K, Rodriguez-Chavez IR, Tosato G, Catanzaro AT, Steinberg SM, Little RF. Treatment of AIDS-related Kaposi’s sarcoma with interleukin-12: Rationale and preliminary evidence of clinical activity. Critical Reviews in Immunology. 2007; 27(5), 401-14.

4. 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.

5. 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.
6. 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.

7. 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.

8. 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.

Further Information

Faculty Website

Principal Investigator Webpage