The focus of translational research in my laboratory is on gaining an understanding of the role that iron transport and genomic regulation of iron metabolism play in chronic inflammatory conditions. Iron is essential for all metabolic and respiratory processes but requires tight cellular compartmentalization due to its role in generating free radicals via Fenton chemistry. Both iron deficiency and iron excess also cause mitochondrial dysfunction, a factor implicated in chronic disease pathogenesis, but the role of iron in these diseases and their natural history is underappreciated and has not been well studied in humans. In addition, iron regulation has a major impact on innate immunity and the inflammatory response, which we are studying in the setting of HIV infection.
We have exploited common iron-loading nuclear genetic variants, which in the heterozygous state are deemed "nonpathogenic", to study subclinically dysregulated iron metabolism and mitochondrial function in: toxicities of high-dose chemotherapy, etiology and prognosis of estrogen-driven cancers, and most recently, neurotoxicities of antiretroviral drugs used to treat HIV/AIDS worldwide. Our 5-year NIMH-funded project builds on this prior work to evaluate joint effects of iron-related nuclear and mitochondrial genomic variants and the "ferrome" (all iron-regulatory and iron-transport genes) on cerebrospinal-fluid iron transport, neuroinflammation, and neurocognitive disorder in HIV infection.
In a separate CDC-funded study, we have also identified genetic predictors of hemolytic-uremic syndrome caused by infection with Shiga-toxin-producing E.coli.
As a clinician and population-based scientist, I am interested in applying genetic epidemiologic methods to study the role of iron and the mitochondrial genome in a multitude of chronic, complex clinical phenotypes.
The focus of my team's research is on the role that variation in iron metabolism and mitochondrial function (energy production) play in chronic inflammatory diseases and their complications. Of particular interest are HIV-associated neurocognitive disorders (HAND), which remain very common despite highly effective drugs that suppress the virus to undetectable levels. Our goal is to increase awareness of HAND in the HIV-infected population, promote screening for the disorder, and develop new ways to treat individuals at risk for HAND based on genomic factors.