Our Laboratory of Molecular Immunology and Infectious Diseases has two major research interests:

1. Studies of the complications of HIV 

Our research efforts are focused on understanding the pathophysiologic mechanisms underlying the increase in HIV associated comorbidities in the era of suppressive antiretroviral therapy (ART) and seeks to utilize multiple biological immunological, genetic and virological approaches to uncover novel mechanisms driving these perturbations and ultimately identify and test therapeutics that will ameliorate and or prevent these disorders.

Central Nervous System Complications in Treated HIV Infection: HIV is undoubtedly neurovirulent and neuropathogenic. The prevalence of HIV-associated neurocognitive disorder (HAND) remains high (estimated 30–50%) and persists despite plasma HIV RNA suppression with potent combination antiretroviral therapy. These cognitive deficits are not only widespread but impact everyday functioning, and increase morbidity and mortality with critical public health effects. To date, there are no clinically proven therapies for HAND for individuals already on stable, virologically suppressive anti-HIV regimens. Monocytes and macrophages have crucial and distinct roles in tissue homeostasis and immunity and are thought to contribute to HAND pathogenesis by mediating HIV-neuroinvasion, which ultimately leads to HIV in the brain tissue, neuroinflammation and neuronal damage.

Currently we are to investigating the early changes to monocyte/macrophage phenotypes and function  during the earliest stages of acute HIV infection that could be important in the development of cognitive impairment. We are also studying viral mechanisms in pediatric HIV infection that may crucial in the evolution of neuro-cognitive deficits in perinatally infected children.

Others studies include translational clinical evaluations of several therapeutic interventions to reduce these cognitive abnormalities in both HIV infected men and women.

Cardiometabolic Complications in Treated HIV Infection: HIV-infected individuals are also at increased risk for cardiovascular disease (CVD)  and insulin resistance. The causes of these complications are likely multifactorial despite long term ART, monocytes/macrophage perturbations are key mechanisms driving these complications and
the objective to assess the precise functional myeloid properties that are differentially dysregulated by HIV and contribute to the increase in CVD in this population.

2. Studies in HIV Reservoirs and HIV Remission

Persistence of the cellular latent HIV reservoir has been a major barrier to the eradication of HIV. to better understand  the establishment and persistence of HIV reservoirs in the setting of ART and test novel strategies to control and clear virus using both human and animal model systems and novel immune targeted therapeutics.

Our groups is involved in NIH funded studies pursuing novel targets for the therapeutic reversal of T cell immune dysfunction associated with HIV. One proposed strategy is to ‘Shock’ the latently infected cells to flush out virus with latency reversal agents (LRAs). However, the ‘Kill’ component is less well developed. We reveal novel inhibitory checkpoint pathways involved in the suppression of T cell responses during HIV infection, the blockade of which may contribute to the reversal of T cell dysfunction in the control or elimination of HIV infection and other retroviruses.

We are also currently evaluating immunoregulatory proteins to control and clear virus in the CNS compartment.

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