Michael Bukrinsky, MD, PhD, professor of microbiology, immunology, and tropical medicine at the George Washington University School of Medicine and Health Sciences, is conducting two studies focusing on HIV-associated disorders, with the support of grants from the National Institutes of Health (NIH). Bukrinsky was awarded a five-year, $3.5 million grant for “Novel Pathogenic Mechanism of HIV-Associated CNS Neurological Disorders” and a four-year, $2.78 million grant for “Lipid Raft Therapy: A Novel Therapeutic Approach for HIV-Associated Cardiometabolic Co-Morbidities.”
“These grants enable our research team to test an innovative hypothesis regarding the pathogenesis of HIV-associated co-morbidities,” Bukrinsky said. “Over the next few years, we hope to make great strides in breaking down how and why these co-morbidities occur.”
Based on previous research conducted in his lab, Bukrinsky has hypothesized that the key pathogenic factor in these co-morbidities is the extracellular vesicles carrying the HIV protein Nef. These vesicles are released into the blood from HIV reservoirs that persist in HIV-infected individuals treated with anti-retroviral drugs. They impair cellular cholesterol metabolism and change the composition and properties of lipid rafts, cholesterol-rich regions of the plasma membrane. These changes subsequently make cells much more responsive to inflammatory stimuli and promote persistent inflammation, which is a critical factor in these co-morbidities.
“If our proposed studies can confirm this hypothesis, we’ll be able to envision a new line of therapeutic treatments targeting lipid rafts,” Bukrinsky said. “In other words, lipid raft therapy can hold the key for more strategically treating these disorders in patients.”