Research Programs

HIV Neuroinflammation and CNS Reservoirs

Since immunological functions are shaped by the host glycome, it is not surprising that inflammation is associated with aberrant glycosylation. Neuro-inflammation during HIV infection involves complex interactions. Dr Ndhlovu co-leads a study investigating glycomic alterations and neuroinflammatory mechanisms of brain health in HIV in a collaboration with investigators at the Wistar Institute and Mount Sinai.

We are evaluating several strategies in persons with early HIV infection or after long-term antiretroviral therapy to better understand HIV related cognitive deficits. One such approach investigates an immunomodulatory glycoprotein and its ability to reactivate and disable the virus particularly in the central nervous system, an important hiding place for HIV

 

Geriatric NeuroHIV

Because up to one-half of people living with HIV experience cognitive impairment from HIV or related factors, the likelihood for masking and thus delaying the diagnosis of early and Alzhemier’s disease is substantial. Our lab has uncovered epigenetic imprints of HIV associated cognitive impairment and are currently using combinatorial omics tools at single cell resolution to define signatures of HIV associated neurocognitive disorders and Alzhemier’s in the hope this would facilitate clinically relevant diagnostic sorting

 

New developments in stem cell technologies have permitted the differentiation of “cerebral organoids” from induced pluripotent stem cells. Research using cerebral organoids can facilitate advances in host–microbe research and thus provide an unprecedented new opportunity to study underlying mechanisms of HIV-1 mediated brain dysfunction. In a new study our research team is providing novel insights into the pathogenesis of HIV-1 mediated brain dysfunction, the effects of cocaine and HIV-1 latency in the brain and the compounding effects of age.

HIV/Co-infection

HIV/Mtb Children living with HIV even if they are on antiretroviral therapy are much more susceptible to Mycobacterium tuberculosis (Mtb) for reasons that are not well understood. We know little about the specific immune defects caused by HIV that are responsible for the increased susceptibility to Mtb, especially in children. Our group is using nonhuman primates to model HIV/Mtb coinfection of preadolescent children and determine how HIV affects a subset of innate immune cells, and test whether the ability of immunocompromised animals to fight TB is improved if we boost those cells. Building on an established collaboration in Myanmar in south East Asia, our lab is intently focused on examining these innate invariant T lymphocytes in children who are (co)infected with HIV and Mtb.

Emerging Pathogens:

Utilizing molecular, cellular, and genomic methods, we aim to identify novel therapeutics and potential mechanism of action of emerging pathogens such as SARs-CoV-2.