The Ye Lab is interested in how the interaction between genetics and environment affect human variation at the level of molecular phenotypes. To study these interactions, our lab couples high-throughput sequencing approaches that measure cellular response under environmental challenges with population genetics where such measurements are collected and analyzed across large patient cohorts. We have developed novel experimental approaches that enable the large-scale collection of functional genomic data en masse and computational approaches that translate the data into novel biological insights. This approach is used to initially study primary human immune cells in both healthy and diseased patients to understand host pathogen interactions and its role in autoimmunity.

Dr. Young's goal is to better understand the glioblastoma immune microenvironment by studying longitudinal microenvironment evolution and translating these biological discoveries into new therapies for patients with glioblastoma. Projects in the Young Lab use a combination of high-throughput single-cell and spatial analyses from human tissue obtained in the operating room with mechanistic and in vivo experiments from immunocompetent glioblastoma mouse models to explore how resistance mechanisms develop and tumors evade conventional immunotherapies. Currently, their preclinical work has identified IL6 blockade in combination with checkpoint inhibition as a promising strategy for glioblastoma.

In the Zamvil Lab, our group employs models, including relapsing and spontaneous experimental autoimmune encephalomyelitis (EAE) to study activation and regulation of CNS Ag-specific T cells. In our early work, we demonstrated for the first time that autoantigen-specific T cell clones could cause clinical and histologic autoimmunity. In the last several years, we have applied our experience studying T cell recognition of myelin Ags in EAE and MS to identification of T cells that recognize aquaporin-4 (AQP4), the autoantigen in NMO. Our group provided the first evidence that AQP4-specific T cells exist in NMO patients and in mice. Currently, we are examining those elements that control selection of AQP4-specific T cells and evaluating how the gut microbiome may influence development of AQP4-specific T cells.

The Zikherman Lab is interested in understanding how autoreactive B cells, despite chronic antigen engagement of the B cell receptor, are restrained from inappropriate activation and differentiation. We are interested in how this process is disrupted in autoimmune disease, and how tolerance mechanisms can be harnessed to treat autoimmunity. To do so, we are taking advantage of novel reporter mice in which autoreactive B cells are fluorescently marked (Nur77-eGFP BAC transgenic line). Current funded projects include dissecting the distinct roles of the IgM and IgD B cell receptor isotypes in regulating immune responses by autoreactive B cells. More recent work is focused on defining how Nur77 and related orphan nuclear hormone receptors function selectively to restrain activation of chronically antigen-activated B cells.