Precision Immunology Institute at Icahn School of Medicine at Mount Sinai (PrIISM)

Autoimmunity

Autoimmune diseases arise when the body mounts an immune response against a specific organ or tissue. Therapeutic interventions against autoimmunity are hampered because the molecular and cellular entities targeted by the immune system are largely unknown. In addition, how the components of the immune system interact to mediate autoimmune inflammation is not well understood. PrIISM investigators are using multidisciplinary approaches to develop effective treatments for a variety of autoimmune diseases. These include T and B cell autoimmune diseases associated with primary immune deficiencies, rheumatoid arthritis, type 1 diabetes, multiple sclerosis, and autoimmune liver diseases.

Basic and clinical immunologists at the PrIISM Institute are using whole genome and exome sequencing to identify new monogenic causes of autoimmunity; next generation sequencing-based tools for discovering autoantigens; highly multiplexed analytical strategies to generate integrated perspectives onto autoimmune pathogenesis; development of therapeutic monoclonal antibodies; profiling the signatures of cytokines, chemokines and other soluble proteins at the local and systemic level to identify potential autoimmune biomarkers; computational approaches and single cell analyses to improve the diagnosis and individualized therapy of patients with autoimmune diseases. This collective approach by PrIISM scientists is aimed towards elucidating autoimmune disease pathogenesis and development of improved diagnostic, prophylactic, and therapeutic modalities.

Investigators with a major focus in autoimmunity include:

Konstantina Alexandropoulos, PhD

Konstantina Alexandropoulos, PhD is an Associate Professor of Medicine at the Department of Medicine/Division of Clinical Immunology at the Icahn School of Medicine at Mount Sinai and head of the T cell-mediated Autoimmunity and Inflammation Laboratory. Research in the laboratory is focused on understanding the process of T cell tolerance and how disturbances in this process results in T cell-mediated autoimmune diseases such as inflammatory bowel disease and autoimmune hepatitis. The laboratory has uncovered mechanisms that regulate central T cell tolerance through the elimination of self-reactive T cells in the thymus, as well as peripheral tolerance that regulate self-reactivity in peripheral organs. Other research projects in the laboratory focus on elucidating T cell development/activation and leukocyte trafficking under physiologic and disease conditions.

Area(s) of Focus:
Autoimmunity
Inflammatory Bowel Disease
Vascular Inflammatory Diseases

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Dusan Bogunovic

Dusan Bogunovic, PhD is the Director of the Center for Inborn Errors of Immunity and an Associate Professor at Precision Immunology Institute, Mindich Child Health Development Institute, Department of Oncological Sciences, Department of Microbiology and Department of Pediatrics at Icahn School of Medicine at Mount Sinai. His research interests encompass human immunogenetics, infectious and inflammatory diseases, cancer immunology, Type I IFN mediated inflammation and drug discovery.

The Bogunovic Lab

The Bogunovic lab focuses on the study of human immunogenetics. We aim to improve understanding of the human immune system by studying:

  1. Individuals with rare auto-inflammatory syndromes
  2. Individuals with severe clinical presentations of infectious diseases
  3. Developing broad-spectrum antiviral therapeutics.
  4. Understanding immune system in Down syndrome

To dissect these phenotypes and develop therapeutics we use genomic, genetic, molecular biology, cellular biology, immunology and clinical tools.

Area(s) of Focus:
Immunodeficiency
Autoimmunity

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Minji Byun, PhD

Minji Byun, PhD is an Assistant Professor of Medicine at the Precision Immunology Institute at the Icahn School of Medicine at Mount Sinai. The Byun laboratory studies genetic basis of rare immune disorders, including, but not limited to, primary immunodeficiency disorders and lymphoproliferative diseases. This lab investigates both inherited (germline) and acquired (somatic) mutations as cause of disease, which is identified using various human genetics tools including whole genome sequencing. The Byun laboratory also conducts functional studies of putative causative variants to validate their pathogenicity, and to elucidate molecular and cellular mechanisms underlying immune dysregulation.

 

Area(s) of Focus:
Immunodeficiency
Autoimmunity 

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Paolo Cravedi, MD, PhD

Dr. Paolo Cravedi is a scientist physician with a strong interest in kidney transplantation and autoimmune glomerular diseases. During his clinical training as nephrologist in Italy, he designed clinical research studies in kidney transplant recipients and in individuals with renal diseases aimed at prolonging survival of the graft or the native kidneys, respectively. His studies have contributed to defining the organ allocation system currently used in many countries around the world.

He subsequently completed his postdoctoral training at the Icahn School of Medicine at Mount Sinai, where he identified unanticipated immune effects of erythropoietin. While Dr. Cravedi’s lab is still interested in understanding the mechanisms of all reactive immune responses, it has more recently expanded its focus to study the pathogenesis of autoimmune glomerular disease.

Area(s) of Focus:
Transplant
Autoimmunity

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Charlotte Cunningham-Rundles, MD, PhD

Primary immune deficiency diseases, first recognized more than six decades ago, include over 300 genetic defects, have provided unique and unparalleled opportunities to study the cellular, biochemical and molecular mechanisms required for a functional immune system. While individually rare, collectively these defects occur in about one out of 10,000 individuals and are found in infants, children, and adults of all ages. Our understanding of immunity owes much to human PIDD; these diseases have elucidated both common and rare defects of adaptive immunity and have opened the field of innate immunity in humans, a currently very rapidly expanding field. The Primary Immune Deficiency Program at the Icahn School of Medicine at Mount Sinai is now a 950 patient service, spanning medicine, pediatrics, and laboratory research. This program is based on a steady stream of new referrals from New York, the surrounding states, and other countries. Based on this work, Dr. Cunningham-Rundles has been continuously funded by the NIH for clinical research studies on human immune defects, while providing an interface for medical and post graduates, T32, and MD, PhD, and fellowship training programs. While there have been amazing advances in the understanding of many primary immune defects, the most common immune defects, those which impair B cell function, are still largely uncharted territory. These types of immune defects often become apparent in adult life and yet are considered primary immune defects with genetic basis. Our current work has identified selected genetic, cellular and micro-environmental influences are critical for normal B cell development and that defects in these processes result in immune deficiency, autoimmunity, and many facets of immune dysregulation.

Area(s) of Focus:
Allergy
Autoimmunity
Immunodeficiency 

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Percio Gulko, MD

The Gulko laboratory focuses in rheumatoid arthritis and other forms of inflammatory arthritis, particularly in the mechanisms regulating disease severity and joint damage. The laboratory has developed a discovery strategy that uses genetic and genomic studies with synovial tissues and cells, as well as functional studies with synovial cells and Tregs. These strategies led to the discovery of a new role for the cation channel TRPV2 in the regulation of the destructive and invasive behavior of synovial fibroblasts and in arthritis. The lab recently positionally identified and functionally characterized the new arthritis gene HIP1, and identified new roles for nuclear receptors such as VDR and LXR, and CXCR3 in the regulation of synovial cell invasion. The laboratory aims to identify new key arthritis genes, characterize their function in Tregs and synovial cells and develop new and better treatments for patients. We have strong on-going collaborations within the Immunology Institute and with the Genomics Institute and Drug Discovery Institute.

Area(s) of Focus:
Autoimmunity

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Dirk Homann, MD

Trained as a physician and immunologist/virologist in Berlin, Boston, Paris and La Jolla, Dr. Homann has a long-standing interest in autoimmune and infectious disease, in particular the generation, maintenance, modulation, pathogenic potential and protective capacity of specific T cell immunity. Dr. Homann began his work as an independent investigator at the University of Colorado, joined the faculty at Mount Sinai in 2014, and was promoted to full Professor with tenure in 2019. Active areas of preclinical investigation include T cell memory; the role of various accessory pathways (chemokines, CD4+T cell help, SLAM family receptors, adenosine, complement system) in regulation of CD8+T cell responses to acute and chronic viral infections; and the concurrent therapeutic modulation of immune responses and beta cell survival in type 1 diabetes (T1D). The overarching goal of these endeavors is the development, adaptation and optimization of therapeutic strategies that effectively curtail (autoimmunity) or embellish (infectious disease) T cell responses with prophylactic and/or curative intent. Over the past decade, Dr. Homann has expanded his research program to encompass a broader context of pancreatic islet cell biology and histopathology in human T1D, and he has launched multiple collaborative efforts to better leverage complementary expert knowledge, unique technology access and more effective overall implementation of research strategies.

Area(s) of Focus:
Autoimmunity

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Amir Horowitz, PhD

Amir Horowitz, PhD is an Assistant Professor of Oncological Sciences at the Precision Immunology Institute at the Icahn School of Medicine at Mount Sinai. Dr. Horowitz’s laboratory studies human NK cells and the genetic and environmental determinants underlying their education and ability to respond in dynamic environments. Dr. Horowitz’s work is contributing to developing an understanding of adaptive NK cells and their roles in microbial infections, cancers, autoimmunity as well as following vaccination and hematopoietic cell transplantation (HCT). He was the first to demonstrate adaptive roles for NK cells in vaccine settings as a strategy to potentiate T cell memory and also pioneered the first studies of human NK cells by CyTOF. His research has led to the identification and characterization of numerous NK cell subsets with unique activity and antiviral (and anti-tumor) potential.

Area(s) of Focus:
Autoimmunity
Cancer Immunology

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Seunghee Kim-Schulze, PhD

Seunghee Kim-Schulze, PhD, is a Facility Director of Human Immune Monitoring Center (HIMC) and assistant professor of Medicine (Hem/Onc division) at the Icahn School of Medicine at Mount Sinai in New York. Dr. Kim-Schulze graduated with a PhD in biochemistry at University of Illinois, and undertook postgraduate fellowship training at the Northwestern medical school, Imperial College in London, UK and Columbia University Cancer center in New York, focused on cellular immunology in cancer. She was recruited to the Icahn School of Medicine at Mount Sinai in 2009 to establish the human immune monitoring facility under the guidance of Dr. Miriam Merad with the mission of identification of novel immune biomarkers of disease and response to therapy in patients with cancer and inflammatory disease. Dr. Kim-Schulze studies critical immune responses in cancer patients undergoing investigational cancer vaccines, check point blockade and the combinatorial therapies via the genomic, cellular and proteomic analysis. Dr. Kim-Schulze has developed multiple clinical protocols for the trials for the cancer immunotherapies and conducted laboratory correlative studies leading to peer-reviewed publications. She has identified the high PD-1 expression in tumor infiltrating immune cells of melanoma patients had poor prognosis compare to the ones with low level of expression before anti-PD-1 antibody became the revolutionary immune modulating FDA-approved for multiple indications. Her work also supports shared immune signatures between various cancers and proinflammatory disease. Currently, she is profiling the signatures of cytokines, chemokines, and other soluble proteins at the local and systemic level to identify the potential biomarkers in various disease including cancer, inflammatory bowel disease, autoimmune, neurology, psychiatry, and cardiovascular disease.

Area(s) of Focus:
Autoimmunity
Cancer Immunology
Inflammatory Bowel Disease
Neuroimmunology
Transplant 

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Sergio Lira, MD, PhD

Dr. Sergio Lira received his MD from the Universidade Federal de Pernambuco in Brazil (1982) and his PhD in Physiology and Pharmacology from the University of California at San Diego (1988). He did his postdoctoral training at the Roche Institute for Molecular Biology in Nutley, NJ. After his postdoctoral training he worked for 11 years in the pharma sector, first at Bristol-Myers Squibb (1992-1996) and then at Schering-Plough (1996-2002). Dr Lira joined Mount Sinai in 2002 as the Irene Diamond Associate Professor of Immunology. In 2007 he became the co-Director of the Immunology Institute (with Dr. Lloyd Mayer), and in 2013 was promoted to Director, a position he occupied until 2016. He is currently The Leona M. and Harry B. Hemsley Charitable Trust Professor of Immunology. His research focuses on the role of immune cells and the microbiome in mucosal inflammation and cancer. He has organized international meetings in this field, including the 2003 Keystone Symposium on Chemokines and the 2006 Gordon Research Conference on Chemotactic Cytokines. He was elected to the Henry Kunkel Society in 2006 and to the Association of American Physicians in 2008. Dr. Lira was a Visiting Professor at the Southern Medical University in Guangzhou, China (2013-2016) and is a member of the Board of Scientific Counselors of the National Cancer Institute (2013-present).

Area(s) of Focus:
Inflammatory Bowel Disease
Autoimmunity
Cancer Immunology
Microbiome
Skin Inflammatory Disease

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Headshot of Robert Samstein, MD, PhD

Robert Samstein, MD, PhD is a Radiation Oncologist in the Department of Radiation Oncology at Mount Sinai and a physician scientist with a laboratory in the Precision Immunology Institute at the Icahn School of Medicine at Mount Sinai. Dr. Samstein completed his graduate work with Alexander Rudensky studying the development and function of regulatory T cells. He completed his transitional year internship and residency in Radiation Oncology at Memorial Sloan Kettering Cancer Center in New York, NY. During residency, he conducted laboratory research with Dr. Timothy Chan investigating predictors of response to immunotherapy as part of the American Board of Radiology Holman Research pathway.

Dr. Samstein’s research interests are focused on understanding the interaction between the patient’s immune system and cancer cells in the tumor, elucidating the role of the DNA damage repair and response pathways in altering the tumor’s ability to be recognized and attacked by the immune system. His laboratory will work to identify new strategies to harness the immune anti-tumor response and expand the therapeutic window of traditional immunotherapies.

Area(s) of Focus:
Cancer Immunology
Autoimmunity

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Hideki Ueno, MD, PhD

Hideki Ueno, MD, PhD, is Professor at the Department of Microbiology at ISMMS and the most recent faculty recruit of GHEPI. Dr. Ueno’s laboratory is focused on understanding dendritic cells and CD4+ helper T cell subsets in humans, an area in which he is an internationally renowned expert, with an overall goal of understanding the adaptive immune system in healthy human subjects and determining how their alterations are associated with vaccine responses and various human diseases. Dr. Ueno successfully secured grant funding while at Baylor, allowing him to establish a robust research program there. He has also obtained funding from NIH and non-federal sources like the Lupus Research Institute.

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