The Sarwal Lab's research is based on computational approaches for analyzing public and lab developed genomic, proteomic, single cell sequencing, cyTOF, metabolomic and microbiome data and its applications to diagnosing renal and transplant injury as well as an emphasis on drug repositioning and new drug design. We focus on the application of novel, high throughput technologies to harness the entire complement of genes, proteins, metabolites and antibodies, to generate new hypotheses for unraveling the underlying mechanisms of complex human diseases. Much of the work focuses on human organ transplantation , and the research efforts of the lab have resulted in a new understanding of the role of B cells, microRNAs, non-HLA antibodies and proteins in acute graft rejection; the prediction of chronic rejection and recurrent FSGS and new onset diabetes after transplantation (NODAT), and the identification of new drugs and drug targets for organ transplant recipients. The goal is to improve the quality of care and life of the patient and to assist the physician in improved and targeted management of the patient, such that there is reduced recipient morbidity and improved quality of life.

The Scharschmidt Lab studies the cellular and molecular mechanisms mediating the adaptive immune response to skin commensal bacteria in order to elucidate the role of microbes in skin homeostasis and inflammatory skin disease. Research in our lab aims to: 1) define host pathways and immune cell populations that facilitate establishment of adaptive immune tolerance to skin commensals; 2) identify commensal-derived molecules that influence the development and function of adaptive immune cell populations in the skin; 3) elucidate how skin-specific structures, such as hair follicles, and the integrity of the skin barrier influence host-commensal dialogue in this tissue. Our scientific approach capitalizes on genetic manipulation of skin commensal bacteria, transcriptional profiling of both host and microbial cells and in vivo models to dissect the antigen-specific response to skin commensal organisms.

The Schjerven lab studies normal and malignant immune cell development with a focus on transcriptional regulation, and the molecular mechanisms underlying how mutations in key regulatory factors can cause disease. The transcription factor Ikaros, encoded by the IKZF1 gene, is a major focus of ongoing work. Due to the many roles of Ikaros in blood cell development and function, our lab has several diverse and complementary research projects.

The Sheppard Lab's research focuses on the in vivo roles of members of the integrin family, the biologic and therapeutic significance of integrin-mediated activation of transforming growth factor beta, and the molecular mechanisms underlying tissue fibrosis. One aim of the research is to identify new therapeutic targets to improve the treatment of common disorders including tissue fibrosis, cancer and asthma. The work begins with basic investigation of how cells use members of the integrin family to detect, modify and respond to spatially restricted extracellular clues and how these responses contribute to the development of common diseases.

The Shum Lab's research lies at the intersection of autoimmunity and pulmonary disease.

The Sil Lab studies the fungal pathogen Histoplasma capsulatum, which is a soil organism that can infect and colonize cells of the innate immune system after inhalation into mammals. Their research is driven by two key questions. First, how do cells sense temperature and make a developmental switch from the soil to the host program? They focus on temperature because it is a sufficient signal to recapitulate the morphologic switch bettheyen Histoplasma filaments (the soil form) and yeast (the host form) in culture. This question is critical to understanding the basic biology of Histoplasma as theyll as a number of closely related fungi such as Blastomyces, Coccidioides, and Paracoccidioides, each of which is a ubiquitous pathogen of immunocompetent hosts in endemic areas. In fact, one of the fascinating evolutionary questions about these environmental fungi is how regulatory circuits have evolved to link morphology and virulence programs with growth at host is be an entry point to broader studies of host-fungal interactions, since it will define critical developmental changes that promote the expression of virulence traits, as theyll as delineate molecular landmarks that will allow us to stage the interactions of the fungus with host cells. Second, how does H. capsulatum defy the innate immune response to take up residence, often permanent, in immunocompetent hosts? The past ten years have witnessed an exponential increase in their understanding of the innate immune response to microbes, and yet, in the case of fungi, their insight is rudimentary at best. Their studies explore the molecular communication at the host-pathogen interface bettheyen H. capsulatum and the macrophage. H. capsulatum displays extremely robust macrophage colonization, so it is currently the best fungal candidate to probe the Achilles' heel of these potheyrful innate immune cells and determine novel mechanisms of virulence that have evolved in eukaryotic pathogens.

The Ashouri lab is focused on understanding how aberrant immune cell signaling disrupts immune tolerance, resulting in autoimmune (AI) disease. We are particularly interested in T cell mechanisms that contribute to the onset of rheumatoid arthritis (RA), a debilitating disease affecting millions. A specific aim of the Ashouri lab is to identify antigen-activated T cells in RA in order to capture and profile arthritogenic clones and elucidate the earliest events in disease pathogenesis. Our work takes advantage of a specific reporter of T cell antigen receptor (TCR) signaling. Tracking the expression of this reporter of TCR signaling in murine and human T cells facilitates our ability to identify and study arthritis-causing T cells before and during RA disease development and addresses the following questions: 1) How are T cells that are relatively deficient TCR signaling able to mediate arthritis development? Our lab uses molecular and biochemical techniques to examine how chronic TCR signaling can enhance T cell sensitivity to cytokine signaling and its dysregulation in disease. 2) How are arthritis causing CD4 T cells initially triggered in disease and to what antigen do these T cells respond? We utilize multi-dimensional and high-throughput technologies including paired single-cell RNA and TCR-sequencing from mouse and human samples with significant potential to identify the TCR specificity, gene expression profile, and signaling networks of cells involved in antigen recognition in RA. Our model system provides a platform to track antigen-specific T cell responses in human diseases in which the inciting antigen is not known and could be broadly applied to other AI diseases, transplant rejection, cancer, and even checkpoint blockade.

The Sirota Lab's long-term research goal is to develop integrative computational methods and apply these approaches in the context of disease diagnostics and therapeutics. We are specifically interested in leveraging and integrating different types of omics and clinical data to better understand the role of the immune system in disease. We are developing computational methods and using them to understand immune tolerance in the context of autoimmune disease and non-response (pregnancy, organ transplant, cancer).

The Spitzer Lab is working to develop our understanding of how the immune system coordinates its responses across the organism with an emphasis on tumor immunology. We combine methods in experimental immunology and cancer biology with computation to understand the modes in which the immune system can respond to tumors and to rationally initiate curative immune responses against cancer.

The Suliman lab builds on the foundation of previous human cohort studies to pursue the following directions:From systems biology to innate correlates of TB progression: 1) The lab is following up on candidate pathways identified through systems biology experiments performed on samples from human cohorts of TB progressors and healthy Mtb-exposed counterparts in Sub-Saharan Africa and South America. These genetic and transcriptional profiling studies point to candidate TB risk pathways including sodium/potassium ATPases and tyrosine metabolism enzymes in innate immune populations. The lab is functionally dissecting the roles of these genes using pharmacological inhibitors and CRISPR/Cas9 gene editing of primary human myeloid cells and Mtb infection experiments, followed by analysis of immunological and metabolic profiles, in order to define their roles in TB disease. 2) Point-of-care biomarkers to identify Mtb-exposed individuals at high risk of developing TB disease: Following previous studies on TB biomarkers and COVID-19 diagnostics, the lab leverages international collaborations and systems biology approaches to discover and validate easy-to-use biomarkers to identify individuals at high risk of progression to TB. The studies aim to down-select biomarkers with high accuracy for translation into point-of-care and near-patient prognostic biomarkers in diverse populations for active case finding, including those with other co-infections. 3) T cell immunity to SARS-CoV-2 and Mtb: The Severe Acute Respiratory Syndrome of Coronavirus-2 (SARS-CoV-2) and Mtb are the two leading causes of mortality from infectious diseases globally. Failure to contain SARS-CoV-2 can be a result of the evolution of escape mutations that evade T cell responses. Similarly, in TB, the activation states and memory phenotypes of T cells can determine the quality of adaptive immunity against Mtb. Therefore, the quality and breadth of T cell responses are critical determinants of protection against both pathogens. It is unclear how the co-infections with Mtb and SARS-CoV-2 influence the inflammatory milieu and antigen-specific T cell responses that correlate with protection from progression to TB disease or severe COVID-19. The Suliman lab studies antigen-specific T cell immunity to SARS-CoV-2 and Mtb in the context of co-infection with the two pathogens, evolving SARS-CoV-2 variants, and COVID-19 vaccine rollout.

The Tana Lab researches health equity in autoimmune hepatitis. We follow a diverse cohort of patients and controls and collaborate with other centers internationally. We use biospecimens and novel technologies to improve understanding of mechanisms.

The Tang Lab investigates mechanisms of immunoregulation and incorporates concepts learned in novel therapies for taming immune responses in autoimmune diseases and organ transplantation.