Laboratory of Prasanta Dash, PhD

Research Interests

Our research focuses on understanding how HIV infection and aging interact to drive chronic inflammation, immune dysfunction, and neurocognitive decline in people living with HIV. Using advanced NSG-humanized mouse models and long-term antiretroviral therapy (ART) paradigms, we investigate how persistent HIV reservoirs contribute to accelerated aging, neuroinflammation, and disruptions in brain immune homeostasis. We combine molecular, transcriptomic, metabolic, neuroimaging, and behavioral approaches to define the impact of latent HIV infection on the aging brain and neuro-immune communication. A major goal of our work is to identify biomarkers and therapeutic targets that can improve the management of HIV-associated aging and neurological complications. Ultimately, our studies aim to advance strategies for eliminating HIV reservoirs and preserving brain health in aging individuals living with HIV. The other major focus of our research is to understand the molecular mechanisms underlying HIV therapeutics, drug–drug interactions, and viral eradication strategies. Despite the remarkable success of ART, challenges such as drug adherence, drug resistance, limited penetration into viral reservoirs, and lifelong treatment requirements continue to prevent a cure. Our laboratory works closely with medicinal chemists to evaluate the efficacy of novel long acting and targeted therapeutic approaches that improve drug delivery across cellular and tissue barriers, including sanctuary sites where HIV persists. We investigate how enhanced viral suppression can be combined with innovative gene-editing technologies, such as CRISPR/Cas9, to eliminate integrated HIV proviral DNA and disrupt key pathways required for viral persistence. Using advanced in vitro systems and humanized mouse models, we evaluate these strategies with highly sensitive molecular and virological assays to accelerate the development of functional and sterilizing HIV cure approaches. Ultimately, our goal is to create transformative therapies capable of eliminating HIV reservoirs and achieving long-term virus remission or cure.

Ongoing Projects

• HIV, Aging, and Neuroimmune Dysfunction: Investigating how persistent HIV infection, long-term antiretroviral therapy (ART), and viral reservoirs contribute to accelerated aging, neuroinflammation, and neurocognitive impairment using humanized mouse models.
• Sequential Combinatorial Therapy for HIV Eradication: Developing and testing innovative multimodal therapeutic strategies in humanized mouse models to achieve durable viral suppression, eliminate persistent HIV reservoirs, and identify the cellular and tissue sources of viral rebound following treatment interruption. These studies integrate antiretroviral therapy, targeted drug delivery, and gene-editing approaches to advance HIV cure strategies and improve our understanding of viral persistence
• HIV Reservoir Detection and Targeted Elimination: Evaluating advanced theranostic nanomedicine platforms developed in collaboration with Dr. Howard Gendelman and colleagues to enhance targeted antiretroviral drug delivery, enable real-time tracking of HIV reservoirs, and improve viral suppression within lymphoid tissues and the central nervous system.
• Neuroimmune and Metabolic Profiling of HIV Infection: Studying cytokine networks, immune activation, and metabolic alterations in myeloid, lymphoid, and CNS compartments during HIV infection, treatment, and viral suppression in the context of aging.
• Pharmacodynamic Platforms for HIV Therapeutics: Establishing preclinical testing platforms to evaluate antiretroviral and adjunctive therapies for systemic HIV infection and HIV-associated neurocognitive disorders (HAND).