Traumatic brain injury (TBI) is a devastating condition with limited treatment options. Incidence and long-term consequences of TBI disproportionately burden veterans. This project aims to improve prospects for veterans and other TBI victims by reducing initial brain damage as well as repairing chronic abnormalities in white matter. Neuroinflammation is a major contributor to acute secondary damage, and white matter loss exacerbates the injury over the long term. We propose to address these two aspects by intra-arterially transplanting glial progenitor cells, engineered to express nanobodies, to selectively block neuroinflammation-inducing danger signals. Over the last two decades our research has focused on improving therapeutic agents targeting the brain via an intra-arterial route to facilitate minimally invasive administration of high concentrations of drugs with immediate access within the entire lesion.

Chronic HIV is a serious medical problem for which there is no cure. The reservoir of HIV in the brain is a major challenge, causing high morbidity, and because drugs cannot cross the blood brain barrier, eradication of the virus is impossible. We propose a solution to this problem by intra-arterial transplantation of glial-restricted progenitors, engineered to express HIV neutralizing antibodies. The long-term goal of this research is to control HIV replication in the central nervous system and to treat or prevent HIV-associated neurocognitive disorder in people living with HIV. Accordingly, we hypothesize that sustained release of genetically-encoded broadly HIV-neutralizing antibodies in the brain by ex vivo engineered and transplanted glial progenitor cells can suppress HIV replication and decrease HIV-induced neuropathogenesis.

The Alavi Program focuses on understanding the chronic cerebrovascular consequences of metabolic syndrome and radiation therapy (RT), integrating multimodal imaging approaches to advance early detection and treatment strategies. This research explores the interplay between vascular inflammation, atherosclerosis, and ischemic stroke, particularly in patients with head and neck cancers receiving RT, where increased stroke risk has been observed but lacks mechanistic clarity. Using PET/MRI imaging with tracers such as FDG and NaF, alongside preclinical pig models and prospective clinical studies, this project aims to quantify vascular injury, track disease progression, and establish imaging biomarkers for vascular damage and associated stroke risk assessment. Ultimately, the goal is to develop precise imaging-based stratification tools to improve stroke prevention strategies in high-risk populations.

This research is made possible by a generous gift from Abass Alavi, MD.