Education and career
Miriam Merad received her M.D. from the medical school at the University of Algiers in 1985 and completed her residency in hematology and oncology at the Paris Diderot University. [5] After obtaining a Master's degree in Biotechnology from the Paris Diderot University, she moved to Stanford University to perform a PhD in the laboratory of Edgar Engleman. [6] Merad’s clinical training in Hematology / Oncology and bone marrow transplantation in the Hôpital Saint-Louis and Institut Gustave Roussy in Paris shaped her initial interest in immunotherapy and inspired her move to Stanford to study dendritic cell-based vaccines with Engleman. Realizing that very little was known about myeloid cell development, Merad collaborated with Irving Weissman at Stanford on several studies that contributed to revisions in the understanding of macrophage and dendritic cell ontogeny. [7] She was recruited to ISMMS in 2004 and awarded an Endowed Chair in Cancer Immunology in 2014. [8]
In 2016, Merad was appointed Director of the Immunology Institute at ISMMS, which had been founded by Lloyd Mayer and Sergio A. Lira in 2007. The institute was renamed the Precision Immunology Institute (PrIISM) to reflect a focus on human immunology and translational research. PrIISM has co-founded several programs and centers with other institutes to support collaborations between physicians and scientists and synergy between fundamental, translational and clinical research initiatives. These include the Human Immune Monitoring Center, [9] the Microbiome Translational Center, [10] the Center for Inborn Errors of Immunity, [11] the TARGET and INTERACT programs [12] and the Center for Computational Immunology. [13]
In August 2023, Merad became the founding Chair of the Department of Immunology and Immunotherapy (DII), a new research department launched at ISMMS focusing on understanding the fundamental biology and impact of the immune system on human health and disease.
In April 2024, Merad was named the Dean for Translational Research and Therapeutic Innovation for the Icahn School of Medicine at Mount Sinai. [14]
Research
Miram Merad's early studies were among the first to identify the mechanisms that control the development and functional identity of tissue resident dendritic cells and macrophages. In particular, her laboratory established the embryonic origin of tissue resident macrophages, [15] microglia [16] and Langerhans cells [17] and investigates their distinct contributions to health and disease. These studies have revealed the critical contribution of tissue resident macrophages to organ physiology including synaptic pruning, gut peristaltism, fat metabolism and vascular integrity. The Merad laboratory identified a new subset of dendritic cells, the tissue resident CD103+ DC lineage, that are specialized in anti-viral and anti-tumor immunity.
Understanding how different myeloid cell subsets drive distinct inflammatory diseases is one focus of the Merad group's research. In 2021, they identified how mutations in mitogen-activated protein kinase pathway genes trigger sensescence in multipotent human hematopoietic progenitor cells that cause multisystem Langerhans Cell Histiocytosis disease by skewing progenitor differentiation towards the mononuclear phagocyte lineage. [18] In 2022, they reported that severe COVID19 disease was associated with a reduction in the tissue-resident lung alveolar macrophages that control tissue repair and an increase in inflammatory monocytes and monocyte-derived macrophages. [19]
The Merad lab has made many discoveries demonstrating the roles that dendritic cells and macrophages play within the tumor microenvironment. [1] The two distinct lineages of macrophages that Merad defined are represented in tumors, with the different developmental origins dictating their specific roles in shaping the tumor microenvironment. In human lung tumors, Merad's team found that tissue-resident macrophages gather near to tumour cells early in tumour formation and make the tumour cells more invasive, and they also activate a regulatory T cell response that protects the tumour cells from the immune system. [20] During tumor growth, the tissue-resident macrophages move to the periphery and monocyte-derived macrophages dominate the tumor-microenvironment. Other recent findings from the Merad team in this area include the identification of TREM2 tumor macrophages as immunosuppressive cells that limit natural killer cell recruitment and activity in a murine model of lung adenocarcinoma, [21] the characterization of mature dendritic cells enriched in immunoregulatory molecules (mregDCs) that limit responses to immune checkpoint blockade, [22] and the niches in tumors in which mregDCs operate. [23]
The Merad lab have reported how aging reshapes macrophages, shifting them from protective tissue guardians into drivers of disease, for example, by fueling cancer risk through immunosuppressive programs [24] and promoting neurodegeneration via senescent monocytes. Merad leads a semi-finalist team in the XPRIZE Healthspan competition, [25] testing strategies to reprogram these aging-linked immune cells for healthier longevity. [26]
In addition to her research program, Merad has published articles on new approaches to cancer immunotherapy clinical trials, [27] how Long COVID can be classified, [28] the importance of immigrants to science in the US [29] , written about her experiences as a mother and a scientist. [30] and founded in 2015 the International Immunoschool [31] with researchers from Sorbonne University in Paris, France, and the University of São Paulo in Brazil,
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