Projects

Role of Platelet-Monocyte Interaction in Promoting Pro-Atherogenic State in HIV-Infected Individuals

Collaborators: Dr. Juilee Thakar (Microbiology and Immunology), Dr. Giovanni Schifitto (Neurology)

This project utilizes multi-omics approaches to investigate transcriptomic and metabolomic changes in platelet-monocyte complexes (PMCs) and non-complexed monocytes in context of HIV infection and atherosclerosis (AS). We have performed single cell RNAseq on flow-sorted monocytes obtained from age and sex-matched study participants categorized by HIV and AS status. Differential genes and pathways of interest associated with PMCs will be validated using an in vitro model system of atherosclerosis (AS).

Brain Structural and Functional Connectome in HIV associated Neuroinflammation

Collaborators: Dr. Giovanni Schifitto (Neurology), Dr. Nasir Uddin (Neurology), Dr. Miriam Weber (Neurology), Dr. Xing Qiu (Biostatistics and Computational Biology), Dr. James McGrath (Biomedical Engineering)

This study investigates the associations between circulating monocyte subsets and cerebral small vessel disease (CSVD) and cognitive performance in people living with HIV infection (PWH). This study has enrolled 100 PWH and equal numbers of healthy control individuals that were followed longitudinally for up to 3 years. Preliminary results indicate that non-classical subset of monocytes is inversely associated with cognition and CSVD in PWH and associate positively with endothelial activation. Using in-house developed 3D model of blood brain barrier (developed by Dr. Jim McGrath) we are currently investigating the migratory propensity of this subset of monocytes and their contribution to neuroinflammation.

Platelet-Medicated Deregulation of Dendritic Cell Function- Implications for Anti-HIV Immune Responses and Immunotherapy

Collaborators: Dr. Benjamin Miller (Dermatology), Dr. Pawel Kalinski, RPCCC, Buffalo, NY

In this proposal we are enrolling study participants with and without HIV infection who are taking anti-platelet medications. Preliminary results indicate that dendritic cells derived from platelet-complexed monocytes are deficient at immune functions. We are investigating if dissociation of platelet-monocyte and platelet-dendritic cell interaction via anti-platelet therapy is a viable approach to rescue monocyte and dendritic cell function during HIV infection. We are also investigating the role pf platelet-origin transforming growth factor ß (TGFß) and Prostaglandin E2 in mediating monocyte and dendritic cell dysfunction.

Brain Signature of SARS-CoV-2 Infection and Its Impact on Long-Term Cognitive Functioning in Older Adults

Collaborators: Dr. Giovanni Schifitto (Neurology), Dr. Nasir Uddin (Neurology), Dr. Miriam Weber (Neurology), Dr. Hongmei Yang (Biostatistics and Computational Biology)

Several recent studies have highlighted long-lasting neurological symptoms associated with severe SARS-CoV-2 infection (Long Covid). Covid infection is also associated with platelet activation, vascular dysfunction and epigenomic changes in monocytes. This study is enrolling older individuals who had severe Covid infection or are experiencing Long Covid to perform comprehensive neuropsychiatric evaluations, MRI imaging to measure markers of cerebrovascular dysfunction and blood-based assays to measure platelet, monocyte and endothelial activation.