Velpandi Ayyavoo

Dr. Ayyavoo is a molecular virologist with over three decades of expertise in HIV-1 virology. Her research laboratory is dedicated to unraveling the intricate mechanisms through which HIV-1 instigates pathogenesis in humans, impacting both the peripheral and central nervous systems (CNS) of people living with HIV (PWH). Leveraging autopsied tissue samples, her laboratory has conducted pioneering investigations revealing substantial alterations in neurons among HIV patients experiencing cognitive disorders, known as HIV-associated neurocognitive disorder (HAND), as opposed to HIV patients without such complications. Her research interests are:

Developing brain organoid model to study HIV-1 associated neurocognitive disorder: Understanding and combating HIV-associated neurocognitive disorder (HAND) is of paramount importance given its increasing prevalence among people living with HIV (PLWH) who are under therapy. However, studying the cellular and molecular events underlying HIV neuropathogenesis poses significant challenges due to the intricate neural-glial networks that operate in tandem within the brain. Despite these challenges, ongoing research endeavors are aimed at unraveling the complexities of CNS diseases, including HAND, through innovative approaches. One such approach involves the utilization of advanced in vitro models, such as brain organoids, which offer a platform for studying neurodegenerative diseases in a controlled laboratory environment. While replicating the intricate neural-glial interactions of the brain in vitro remains a daunting task, brain organoids provide a promising avenue for investigating the cellular and molecular mechanisms involved in HIV neuropathogenesis. Brain organoids, sophisticated three-dimensional miniature models of the human brain grown from stemcells, represent a promising tool for studying neurodegenerative diseases. These organoids offer a unique platform that closely mimics the cellular architecture and functionality of the human brain, providing researchers with the opportunity to observe the progression of neurodegenerative diseases in a controlled laboratory setting. Overall, brain organoids serve as a powerful and ethically viable model system that holds great promise for advancing our understanding and treatment of neurodegenerative diseases. Dr. Ayyavoo’s laboratory is the first to develop the brain organoids with microglia.

Understanding HIV latency in CNS and to develop therapeutic targets to activate the virus:  Despite significant progress in managing HIV-1 infection, eradicating the virus entirely remains challenging. Infected cells persist in various tissue compartments, including the brain, even during combination antiretroviral therapy (ART). The central nervous system (CNS) serves as a viral reservoir, with cellular compartmentalization and limited penetrability of antiretroviral drugs due to the blood-brain barrier. Primary reservoir cells in the CNS include microglia, perivascular macrophages, and astrocytes, yet our understanding of HIV-1 infection in CNS reservoirs remains limited. Studying CNS latency is hindered by the lack of suitable HIV-CNS models. Utilizing a 3D brain organoid model with human microglia sourced from HIV-1 positive donors, we aim to characterize transcriptional changes. This knowledge may lead to the discovery of novel therapeutic interventions targeting latency-inducing and/or silencing antivirals for the CNS compartment. Additionally, we aim to validate and assess whether these target molecules can traverse the blood-brain barrier and effectively reach their intended cellular targets in the brain.