My research career spans over 30 years. It started in Moscow, Russia where, after graduating from the Moscow Medical School with an MD degree in 1978, I defended the PhD thesis in 1984 at the Institute of Molecular Biology, and began working at the Ivanovsky Institute of Virology on the recently discovered virus – Human Immunodeficiency Virus. At that time, HIV research was in its infancy, and diagnostic tools for HIV infection were not widely available even in USA. My group (myself and two graduate students under my supervision) was given a task to develop a test system for HIV infection based on recombinant antigens. In 2 years, we expressed HIV antigens using bacterial and eukaryotic expression systems, and created an ELISA test system for HIV-specific antibodies. For this work I was awarded the highest recognition for Russian young scientists – a state award. And both students successfully defended their PhD thesis.
In 1989 I emigrated to USA and started working on HIV biology as a post-doctoral fellow in the laboratory of Dr. Mario Stevenson in Omaha, Nebraska. During the 2.5 years in this laboratory, I actively participated in developing a new concept in HIV biology – HIV latency. With my participation, the group described HIV latency in CD4+ T cells and identified one of the mechanisms of latency, so called pre-integration latency. These studies provided the basis for identifying resting T cells as the reservoir of HIV. They also introduced the concept of HIV preintegration complex formation and its nuclear import as the critical components of HIV life cycle, and developed several approaches to study these events.
In 1993 I was invited to head Laboratory of HIV Infection in the newly formed Picower Institute for Medical Research in Manhasset, New York, under direction of Dr. Anthony Cerami. During my 10-year tenure at the Picower Institute, my laboratory made a number of highly significant, paradigm-shifting discoveries. We were the first to demonstrate differential effect of chemokines on HIV infection of T cells and macrophages, to show induction of NO in HIV-infected macrophages, to characterize the role of signaling in HIV entry into primary cells, and to identify a series of new anti-HIV agents. My laboratory also worked on the mechanisms of inflammation. This work produced a major discovery: we found that extracellular cyclophilins are potent chemoattractants for immune cells and may contribute to inflammatory reactions in a number of diseases. We also identified CD147 as a receptor for extracellular cyclophilins. Several US and international patents were issued to cover these discoveries.
In 2001 I was invited to join the Department of Microbiology, Immunology and Tropical Medicine at GWU as a tenured Professor and Vice Chair of the Department. Besides my administrative responsibilities, I continued an active research program. My research interests shifted towards studies related to cardiovascular disease in HIV-infected patients, which has become the main clinical problem for HIV patients since the advent of HAART. Studies from my laboratory on pathogenesis of CVD in HIV-infected patients identified a mechanism for virus-induced atherosclerosis, the first direct connection between viruses and heart disease. Studies of the effect of HIV infection on cholesterol metabolism are now the main focus of my lab. Another new major area of interest is HIV-1-associated neurocognitive disease, where we accomplished a major breakthrough by demonstrating a pathogenic mechanism of exosome-carried Nef, which is similar to the mechanism previously established for cardio-vascular disease. These studies led us to propose an innovative hypothesis that provides a common cause for several HIV-associated co-morbidities, including CVD and neuropathology. We proposed that Nef-mediated changes in the structure and function of the lipid rafts, cholesterol-rich plasma membrane domains, is the key pathogenic mechanism responsible for persistent inflammation and functional impairment of macrophages, endothelial cells, neurons, astrocytes, microglial and other cells involved in HIV co-morbidities.
In addition to my research, I am also actively involved in teaching. One of my PhD students, Steven Santos, graduated in 2014 and, following a post-doctoral training at NIH NCI, has become a Scientific Review Officer at NIH CSR. Another PhD student, Ruth Hunegnaw, graduated in 2016, completed her post-doctoral training at NIAID, and is working now at NIH. Now I am supervising another graduate student, Jessica Schenck. An undergraduate student undergoing training in my lab, Christina Darwish, received a GW Undergraduate Research Awards in 2015 and 2016 and is now a student at GWU School of Medicine. STEP-UP minority students, Kiera Williams and Jaden White, were trained in my lab in summers of 2014 and 2017, respectively.
I am the Director of the CFAR Developmental Core were one of my responsibilities is facilitating development of junior HIV investigators. I am also the Chair of the MITM APT Committee, and I am actively involved in mentoring junior investigators, both in my lab and within the CFAR community. I am a member of the SMHS APT Committee, and the Chair of the SMHS Faculty Executive Committee. And finally, I am an active participant in the international collaboration with Russia. In 2019, at my initiative, a Memorandum of Understanding was signed between the Moscow State University and GWU, making plans for active exchange visits of the faculty and students.