Leveraging TCR sequencing to understand autoimmune responses and neurologic disorders

I have more than 15 years of experience of working with mouse models of neuroinflammatory diseases. I am an Assistant Professor in the Department of Neurology (Primary), Division of Multiple Sclerosis, and the Department of Pathology and Immunology (Secondary), The Hope center for neurological disorders, and Bursky Scholar at Center for Human Immunology and Immunotherapy Programs (CHiiPs) at Washington University, School of Medicine St. Louis, MO. I am a recipient of National Multiple Sclerosis Society (NMSS) Career Transition Award (2019-2023), Carol and Gene Ludwig Award for Early Career Research (2022), and Edward Jr. Mallinckrodt New Investigator Award (2023) . My laboratory’s research objective is to understand the adaptive immune responses in health, neurological disorders, and cancer with a specific focus on T cell phenotypes, receptor diversity, and specificity. As a NMSS funded postdoctoral fellow, I complemented my background in EAE and MS with training in antigen specific T cell responses and single cell biology. ​

T cells are a major component of the adaptive immune system, and they recognize a diverse repertoire of antigens through T-cell receptors (TCRs). Major bottleneck in understanding T cell responses in health and disease is the diversity of TCRs and the vast variety of antigens that they can encounter. To circumvent these, I have taken a sequence-based approach to study T cell responses and developed a robust single T cell abTCR sequencing and phenotyping method and a bioinformatic analysis pipeline, which can group TCR sequences into clusters sharing specificity. Further, I have developed unbiased high-throughput technologies to determine antigen specificity of abTCRs. This contrasts with traditional candidate approaches which involved a priori knowledge of the relevant antigens. For the past couple of years, our studies focused on determining the abTCR repertoire, clonal diversity, identifying novel autoantigens in EAE (Saligrama et al., Nature 2019), paired epigenome and TCR profiling in cutaneous T cell lymphoma (Satpathy* and Saligrama* et al., Nat. Medicine, 2018). By employing these technologies, collaboratively I explored T cell responses at a “systems level” in brain aging in mice (Dulken et al., Nature 2019) and Alzheimer’s disease (Gate and Saligrama et al., Nature 2019). Overall, my laboratory’s primary objective is to leverage these technologies and determine the T cells responses and specificity in autoimmunity and neurological diseases (Alzheimer and Parkinson disease).​