Precision Immunology Institute

Microbiome and Host Pathogen Interaction

The ability of our immune system to tolerate commensal microbes and attack pathogenic microbes is a central problem of immunology. Failure to recognize pathogenic microbes can result in disease and death, while immune differentiation driven by commensal microbes might influence complex disease susceptibility. The Precision Immunology Institute (PrIISM) investigators are studying the complex host microbe interactions that promote tolerance or defense.

Laboratories in the PrIISM study human microbiota that accompany chronic diseases, such as inflammatory bowel disease, to better understand how the changes in microbiota contribute to disease. Others are examining what innate and adaptive immune pathways can be exploited to block or clear infectious pathogens. A combination of in vitro studies, animal models, and clinical studies enables PrIISM investigators to examine the mechanisms behind disease and immune protection. PrIISM investigators are at the forefront of cutting-edge clinical studies and trials of fecal transplantation, vaccines, and immunotherapy to treat or prevent infections and complex disease. 

Investigators with a major focus in microbiome and/or host pathogen interaction include:

Nina Bhardwaj, MD, PhD is an immunologist who has made seminal contributions to human dendritic cell biology, specifically with respect to their isolation, biology, antigen presenting function, and use as vaccine adjuvants in humans. She is the Director of Immunotherapy at the Icahn School of Medicine at Mount Sinai (ISMMS) and holds the Ward Coleman Chair in Cancer Research. Dr. Bhardwaj brings expertise in human immunology and a variety of immune therapies, having developed Toll Like Receptor (TLR) agonist- and dendritic cell-based vaccines for the treatment of both cancer and infection in several Investigator-Initiated studies. Dr. Bhardwaj is an elected member of the American Society of Clinical Investigation and the American Association of Physicians, a recipient of the Doris Duke Distinguished Scientist Award and was named one of the Scientific American Magazine’s Top 50 Researchers, receiving the Award for Medical Research in 2004. She received the Fred W. Alt Award for new discoveries in Immunology in 2015 from The Cancer Research Institute. Dr. Bhardwaj is a senior editor of the AACR Cancer Immunology Research journal, senior editor for Frontiers in Immunology and consulting editor for the Journal of Clinical Investigation. She has also served on NIH Study Sections and multiple advisory councils. Dr. Bhardwaj was formerly chair of the Cancer Immunology Steering Committee of the AACR. Dr. Bhardwaj has also successfully acquired multiple federal and foundation grants and has authored over 200 publications.

Area(s) of Focus:
Cancer Immunology 

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The Chen laboratory studies how the human immunodeficiency virus (HIV) exploits immune cell interactions to promote viral dissemination. HIV is a chronic and incurable infection of the immune system that targets the helper CD4 T cells. Our group has studied how HIV induces unique cell-cell adhesions between HIV infected and uninfected CD4 T cells called virological synapses (VS). These contacts induce virus production and facilitate transmission through incompletely characterized pathways. Our live cell imaging studies have uncovered dynamic cellular processes that contribute to VS. VS promote viral diversity and evasion from humoral immune responses and thus are critical to consider in HIV vaccine development. We have also found that other synapses between HIV-infected T cells and non-immune cells, such as those in the kidney can cause end organ pathology known as HIV nephropathy. In addition, we are learning how HIV alters and exploits immune cell migration using advanced intravital imaging approaches in mice engrafted with human immune cells—so called humanized mice. Humanized mouse HIV infection models provide a system to study actively and latently infected cells to explore the molecular basis of HIV latency and persistence. These models may help us to identify and test new strategies to prevent and cure HIV.  

Area(s) of Focus:
Microbiome and Host Pathogen Interaction
Immunodeficiency 

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Jose C. Clemente, PhD is an Assistant Professor of Genetics & Genomic Sciences and Immunology and member of the Precision Immunology Institute at the Icahn School of Medicine at Mount Sinai. Dr. Clemente's laboratory studies the human microbiome and its effect on human diseases. His laboratory has made critical findings in characterizing the microbiome of human populations and in understanding how deviations from microbial homeostasis is associated with immune disorders. Dr. Clemente's laboratory has also pioneered studies on how to modify the microbiome, both in early life and in adulthood, in order to restore homeostasis. He is an Associate Editor of Microbiome and mBio, and has published over 70 articles in high profile journals.

Area(s) of Focus:
Allergy
Inflammatory Bowel Disease 
Microbiome and Host Pathogen Interaction 

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Jeremiah Faith, PhD received his PhD in Bioinformatics and Systems Biology from Boston University. He did his postdoctoral training in the laboratory of Jeffrey Gordon at Washington University in St. Louis Medical School with a focus on the structure and function of the gut microbiome in healthy individuals. He is currently an Assistant Professor in the Immunology Institute and the Institute for Genomics and Multiscale Biology in the Icahn School of Medicine at Mount Sinai in New York. He is also director of the Icahn School of Medicine at Mount Sinai’s Gnotobiotic Facility and co-director of the Immunology Training Area. Dr. Faith’s lab studies the interactions between diet, gut microbes, and host physiology with an emphasis on Inflammatory Bowel Disease.

Ongoing research in the lab includes:

  • Quantifying the influence of diet and the gut microbiota on host health and disease.
  • Understanding the impact of interpersonal variation in gut microbiome composition on host phenotypic variation.
  • Optimizing the engraftment of live bacterial therapeutics.
  • Tracking the stability and transmission of the human gut microbiota. 

Area(s) of Focus:
Inflammatory Bowel Disease
Cancer Immunology
Microbiome and Host Pathogen Interaction

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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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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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Dr. Irene Ramos’ research primarily focuses on the understanding of interaction of viruses, specifically influenza A viruses (IAV) and dengue virus, with the innate immune system. She uses mainly primary human systems to study the mechanisms and profiles of activation of the cellular response upon infection, how these responses inhibit virus replication, and how the viruses counteract the innate immune response to favor their spread in the host.

Dr. Ramos has made multiple contributions to this field. In particular, she described a role of the avian and human-like receptor specificity of IAV in the induction of proinflammatory responses in dendritic cells (DCs), macrophages, and human primary tracheo-bronchial cells. She has done expansive work at characterizing the immunomodulatory function of the viral proteins PB1F2 and NS1 from IAV in DCs. She also has contributed to the evaluation of vaccines against influenza viruses in immunocompromised children, pregnant HIV+ women, and against leishmaniasis in domestic dogs. Recently, she performed immune phenotyping of dengue and Zika virus infections in ex vivo human systems using mass cytometry (CyTOF) and other techniques, showing that serotype-specific responses could be associated with virus pathogenesis. In addition, Dr. Ramos is the project coordinator of the Dengue Human Immunology Project Consortium (DHIPC), with a central role in the administration and management of the Center.

Currently, Dr. Ramos continues to focus on the interaction between IAV and human primary systems through the use of novel experimental technologies and integration with computational methods.

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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