Susan Westmoreland, VMD
Department of Pathology, Harvard Medical SchoolThe New England Primate Research Center
Neuropathology of HIV and SIV infections and AIDS
Explore the molecular and cellular bases of neuropathologies associated with HIV and SIV infections, including encephalitis and dementia.
New treatments and screening methods for neuronal dysfunction in AIDS patients; identify new biomarkers for metabolic diseases and aging that require access to postmortem tissues and brain samples from elderly rhesus monkeys possessing a spectrum of diseases
Dr. Westmoreland has valuable expertise in neuronal pathologies associated with SIV infections of non-human primates, comparative pathology, microscopy, and imaging modalities. Her lab is investigating the SIV-related biological mechanisms responsible for eliciting neuronal insults, and capitalizing on this knowledge to develop screening methods and new therapeutic modalities. Her research into AIDS-associated neuropathogenesis represents a viable market opportunity for new diagnostics and pharmacological agents, and Dr. Westmoreland’s SIV studies are at the forefront of this field. In a separate research program amenable to corporate partnerships, Dr. Westmoreland has assembled a repository of brain samples, tissue samples, and metabolic data for a series of rhesus monkeys with a range of diseases, such as Type II diabetes. These data and tissue samples are valuable resources for studies aimed at correlating genetic and protein markers with disease development and prognosis.
Current Research Interests
Dr. Westmoreland is investigating the detrimental effects of SIV infection on the CNS in non-human primates. The neuronal effects induced by HIV and SIV infections are associated with CNS dysfunction, even though they do not directly infect neurons. The CNS injuries develop in response to the influx of monocytes and macrophages, and the concomitant release of pro-inflammatory cytokines. She is studying the molecular basis of the dynamic cycle of injury and repair in the CNS following HIV and SIV infections.
- The lab is studying synaptodendritic injury that manifests in HIV-infected patients and SIV-infected non-human primates. The lab uses particular neuronal metabolic markers, such as N-acetylaspartate and synaptophysin, to screen methods for monitoring synaptic injury and recovery.
- The lab is trying to identify key molecules that are critical for repairing the neuronal injuries, including the neurite growth-associated protein GAP-43, to develop strategies for enhancing the repair process.
Dr. Westmoreland has a longstanding interest in employing simian immunodeficiency virus (SIV) infection of non-human primates as a model for studying human immunodeficiency virus (HIV) induced neuronal pathology and AIDS. She directs various core facilities, including microspcopy, molecular, and clinical pathology services, for other laboratories’ non-human primate studies.
Her work in SIV-related neuropathogenesis encompasses a range of disorders, including encephalitis, dementia, and other abnormal central nervous system (CNS)-related phenomena. She has directed and contributed to several studies investigating AIDS-related encephalopathy. In a recent study, Dr. Westmoreland along with her Massachusetss General Hospital (MGH) collaborators Dr. Gonzalez, Dr. Lentz, and Dr. Ratai, compared the levels of brain metabolites in brains from normal macaques and SIV-infected macaques. Their findings revealed three distinct metabolic profiles that corresponded to animals that were uninfected, SIV-infected with AIDS but without encephalitis, and SIV-infected with encephalitis. Especially important data demonstrated the effectiveness of the N-acetylaspartate-to-creatine ratio in diagnosing the extent of encephalitis. The doctors used magnetic resonance spectroscopy longitudinally on live animals and found that CNS injury and encephalitis in SIV-infected monkeys could be resolved with a combined antiretroviral therapy (CART) of drugs that did not cross the blood-brain barrier. Instead, the CART targeted infected monocytes in the periphery. SIV-infected monocytes that migrate to the brain are largely responsible for CNS function deterioration in SIV-infected monkeys.