The Wilson Lab's research is focused on infectious and autoimmune diseases of the central nervous system. Our lab applies metagenomic and immune repertoire sequencing techniques as well as phage display autoantibody and viral antibody discovery technologies to enhance our understanding of the causes and immunopathogenesis of multiple sclerosis as well as autoimmune and infectious causes of meningoencephalitis. To fuel these inquiries, we have a large effort to biobank blood and cerebrospinal fluid samples from over 1,000 patients with a variety of neuroinflammatory diseases.

The Wolkowitz Lab's broad focus is the identification of moderators and mediators of stress effects on psychiatric and comorbid physical health, with a goal of identifying novel targets for therapeutic intervention. Our������focus has been on the mechanisms of hormonal, inflammation, and stress-related mental illnesses and on peripheral-brain interactions that affect both somatic and mental health. We������have mainly applied this line of investigation to major depression and PTSD, with a focus on accelerated biological aging. We are interested in uncovering mechanisms by which depression and other serious mental illnesses become associated with a surfeit of diseases of aging in affected individuals. Our group has specific knowledge of biomarkers that are relevant to these neuropsychiatric and other illnesses, such as inflammation, steroids and neurosteroids, cellular aging (telomere length and telomerase activity; epigenetic aging), oxidative stress, neurotrophic factors and metabolomtabolomics and mitochondrial functioning. Our lab is beginning to additionally explore the gut-microbiome-brain axis in major depression. We have just concluded a 10-year NIMH study,�"Cell Aging in Major Depression,"��and are fitting our data into mechanistic models that may clarify the mediators and mechanisms of illness in the context of stress and psychiatric illness.

The Woodruff Lab's������research comprises both������clinical and translational research into a range of lung diseases including asthma, chronic obstructive pulmonary disease (COPD), and granulomatous lung diseases (e.g. sarcoidosis and hypersensitivity pneumonitis). These studies fall into three specific categories: 1) the identification of distinct molecular sub-phenotypes of these diseases;������2) the elucidation of disease-relevant mechanisms of airway inflammation and remodeling in the lung;��

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.