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

Vascular Inflammatory Disease

The development of anti-inflammatory therapies in vascular disease like atherosclerosis, a chronic inflammatory disease in response to vascular lipid accumulation, has proven highly challenging. The limited access to human tissue samples and lack of innovative high-dimensional technologies to examine them may have contributed to the lack of significant conceptual advances in the field. Only recently, IL-1β inhibition has proven successful in preventing recurrent cardiovascular events in patients with recent myocardial infarction and elevated hsCRP. Yet the success of this therapy, although significant, is still limited to subsets of patients with vascular atherosclerosis.

PrIISM joined efforts with the Cardiovascular Research Center to build a state of the art Vascular Inflammatory Disease (VID) program that assemble a multidisciplinary team of basic vascular biologists and immunologists, computational scientists, clinical cardiologists, vascular surgeons, and experts in vascular imaging with the common goal to develop scientifically-based strategies that will help the design of precise immunotherapies against inflammatory vascular disease. VID members focus on ways to identify new immune cell subpopulations and dysregulations locally within the diseased vessel (i.e. atherosclerosis lesions) that will help the design of precise and molecularly targeted immune modulatory treatments to prevent lesion growth and rupture. We have developed a translational platform based on the use of non-invasive imaging modalities to validate that the anti-inflammatory efficacy of new candidate compounds in mice and translational large animal model of atherosclerosis.

Investigators with a major focus in vascular inflammatory disease include:

Chiara Giannarelli, MD, PhD is an Assistant Professor of Medicine, Cardiology and of Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai. Dr. Giannarelli’s Laboratory studies the role of innate and adaptive immunity in atherosclerotic cardiovascular disease. Her Laboratory focused on the identification of new immune cell subpopulations and dysregulations within the diseased atherosclerotic vessel to help the design of precise and molecularly targeted immunemodulatory treatments to prevent lesion growth and rupture. Using computational drug repurposing analysis Dr. Giannarelli and her collaborators have identified several compounds predicted to influence atherosclerosis. The laboratory is validating the anti-atherosclerotic efficacy of selected candidate drugs using a translational platform based on the use of non-invasive imaging modalities to validate that the anti-inflammatory efficacy of new candidate compounds in mice and translational large animal model of atherosclerosis. Dr. Giannarelli has obtained NIH funding for her studies immune mechanisms of cardiovascular disease.

Area(s) of Focus:
Vascular Inflammatory Diseases 

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Miriam Merad, MD, PhD is the Icahn School of Medicine at Mount Sinai Chair Professor in Cancer Immunology and the Director of the Precision Immunology Institute at the Icahn School of Medicine at Mount Sinai in New York. Dr. Merad obtained her MD at the University of Algiers, Algeria. She did her residency in Hematology and Oncology in Paris, France and obtained her PhD in immunology in collaboration between Stanford University and University of Paris VII. She was recruited to the Icahn School of Medicine at Mount Sinai in 2004 and was promoted to the rank of Associate Professor with Tenure in 2007 and to Full Professor in 2010 and in 2014, she obtained an Endowed Chair Professor in Cancer Immunology.

Dr. Merad’s laboratory studies the contribution of macrophages and dendritic cells to Cancer and Inflammatory disease in mice and Human. Dr. Merad’s pioneering work mapping the regulatory network of dendritic cells (DCs) resulted in identification of a lineage of DC, the CD103+ DC, that is now considered a key target to improve antiviral and antitumor immunity. Another of her key discoveries is that, contrary to the previously-held beliefs that monocytes are precursors of macrophages, she found that tissue-resident macrophages in fact arise from embryonic precursors that take residence in tissues prior to birth and are maintained independently of adult hematopoiesis. These insights are now being used to develop novel macrophage and dendritic cell-specific targets for the treatment of Cancer and Inflammatory diseases. 

Dr. Merad has authored more than 160 primary papers and reviews in high profile journals. Dr. Merad receives generous funding from the National Institutes of Health (NIH) for her research on innate immunity and their contribution to human disease, and belongs to several NIH consortia. She is an elected member of the American Society of Clinical Investigation and lectures around the world on her work. 

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

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Adeeb Rahman, PhD is a broadly trained cellular immunologist with a research focus on the role of innate inflammation in shaping adaptive immunity in a range of disease settings and a keen interest in technology, engineering, and assay development. As Director of Technology Development for Human Immune Monitoring Center (HIMC) at the Icahn School of Medicine at Mount Sinai, his overarching focus is on implementing and optimizing advanced technology platforms, particularly flow and mass cytometry (CyTOF), to enable analyses of the complexity and heterogeneity of the immune system across diverse clinical conditions.

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

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