Molecular Medicine and Infectious Diseases Laboratory
Research in the Molecular Medicine and Infectious Diseases Laboratory focuses on the mitochondrial etiology of HIV complications in clinical studies using a mechanistic approach.
The Laboratory Director is Dr. Mariana Gerschenson.
Examples of some of the research projects include:
- To develop some novel methodologies and techniques for evaluating blood sera biomarkers of recent alcohol use and liver mitochondrial toxicity for the Veterans Aging Cohort (VACS). The group has established methodologies to measure the mitochondrial isoform of aspartate aminotransferase (AST), cytoplasmic AST, and total AST in sera and mitochondrial DNA (mtDNA) copies/cell in peripheral blood mononuclear cells (PBMCs). Dr. Gerschenson has shown that both mitochondrial AST and mtDNA levels are associated with indicators of alcohol consumption amoung HIV positive subjects.
- To evaluate whether new HIV therapeutic drugs, like abacavir or tenofovir, are inducing mitochondrial dysfunction in HIV patient's fat and PBMCs. This is a highly significant issue in the therapy of HIV patients, since NRTIs are mitochondrially toxic. Mitochondrial endpoints include measuring mtDNA copies/cell, mitochondrial RNA gene expression (microarrays), mitochondrial oxidative phosphorylation enzyme activities, mitochondrial oxidative stress (mitochondrial 8-oxo-deoxyguanine), and apoptosis.
- To evaluate if acetyl-L-carnitine will improve HIV-peripheral neuropathy and measure mitochondrial parameters over a 24 week period. Carnitine is known to improve beta-oxidation and may result in normalization of energy production in HIV patients with peripheral neuropathy.
- To study the contribution of macrophages to the development of HIV-lipoatrophy. In a cross-sectional study, Dr. Gerschenson's group is measuring if macrophages are increased in HIV+ lipoatrophic patients when compared to HIV seronegative and various HIV+ control groups. The adipose tissue is being separated into adipocyte, pre-adipocyte and macrophage cellular components and the cytokine contribution is being measured. Dr. Gerschenson's current research is to elucidate the inter-relationships that may exist between macrophage content, cytokine levels, parameters of mitochondrial dysfunction and apoptosis to better understand the dynamics involved in the pathogenesis of HIV lipoatrophy.