Miram Merad (born 1969)^[1] is a French-Algerian professor in Cancer immunology and the Director of the Marc and Jennifer Lipschultz Precision Immunology Institute (PrIISM) at the Icahn School of Medicine at Mount Sinai (ISMMS) in New York, NY. She is the corecipient of the 2018 William B. Coley Award for Distinguished Research in Basic Immunology^[2] and a member of the United States National Academy of Sciences^[3] and the National Academy of Medicine.^[4]

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, who provided her with the tools to study the origin of macrophages and dendritic cells. Merad's collaboration with Weissman resulted in a series of ontogeny studies that led to the re-writing of textbook chapters describing the origin of macrophages and dendritic cells.^[7] She was first recruited to the ISMMS in 2004 and promoted to the rank of associate professor with Tenure in 2007 and to Full Professor in 2010. She obtained 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 Merad's vision of transforming the institute to encompass a new, dedicated focus on human immunology and accelerating the translation of research advances made in foundational immunology in preclinical models into new therapeutic approaches. Under Merad's leadership, PrIISM has launched and co-founded with other ISMMS institutes, many programs and centers that support highly productive collaborations between physicians and scientists and enhance synergy between fundamental, translational and clinical research initiatives. These centers and programs 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 Icahn Mount Sinai that intends to foster a comprehensive understanding of the fundamental biology and profound impact of the immune system on human health and disease. The DII aims to empower researchers to explore groundbreaking scientific inquiries about the immune system and develop innovative types of immunotherapy.

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,^[14] microglia^[15] and Langerhans cells^[16] 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.^[17] 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.^[18]

The Merad lab has made many discoveries demonstrating the roles that dendritic cells and macrophages play within the tumor microenvironment.^[19] 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 key advances 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 generates detailed transcriptional and epigenetic atlases of dendritic cells and macrophages that are available as resources to uncover new insights into the regulatory networks and molecular identity of these myeloid cells.

In addition to her research program, Merad has published articles on new approaches to cancer immunotherapy clinical trials,^[24] how Long COVID can be classified,^[25] the importance of immigrants to science in the US^[26] and written about her experiences as a mother and a scientist.^[27]

Honors

• Member of the United States National Academy of Medicine.
• Fellow of the Society for Immunotherapy of Cancer Academy of Immuno-Oncology.^[28]
• President of the International Union of Immunological Societies.^[29]
• Member of the American Society for Clinical Investigation.^[30]
• William B. Coley Award for Distinguished Research in Tumor Immunology^[31]
• Member of the United States National Academy of Sciences.^[32]
• Highly Cited Researcher since 2017 Thomson Reuters.^[33]

Notable publications

• Merad, M; Manz, MG; Karsunky, H; Wagers, A; Engleman, EG (2002). "Langerhans cells renew in the skin throughout life under steady-state conditions". Annu Rev Immunol. 3 (12): 1135–1141. doi:10.1038/ni852. PMC 4727838. PMID 12415265.
• Ginhoux, F; Greter, M; Leboeuf, M; Nandi, S; Merad, M (2010). "Fate Mapping Analysis Reveals That Adult Microglia Derive from Primitive Macrophages". Science. 330 (6005): 841–845. Bibcode:2010Sci...330..841G. doi:10.1126/science.1194637. PMC 3719181. PMID 20966214.
• Merad, M; Sather, P; Helft, J; Miller, J; Mortha, A (2013). "The dendritic cell lineage: ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting". Annu Rev Immunol. 31: 563–604. doi:10.1146/annurev-immunol-020711-074950. PMC 3853342. PMID 23516985.
• Hashimoto, D; Chow, A; Noizat, C; Teo, P; Merad, M (2013). "Tissue-resident macrophages self-maintain locally throughout adult life with minimal contribution from circulating monocytes". Immunity. 38 (4): 792–804. doi:10.1016/j.immuni.2013.04.004. PMC 3853406. PMID 23601688.
• Lavin, Y; Winter, D; Blecher-Gonen, R; David, E; Merad, M (2014). "Tissue-resident macrophage enhancer landscapes are shaped by the local microenvironment". Cell. 159 (6): 1312–1326. doi:10.1016/j.cell.2014.11.018. PMC 4437213. PMID 25480296.
• Lavin, Y; Merad, M (2019). "Innate Immune Landscape in Early Lung Adenocarcinoma by Paired Single-Cell Analyses". Cell. 169 (4): 750–765. doi:10.1016/j.cell.2017.04.014. PMC 5737939. PMID 28475900.
• Casanova-Acebes, M; Merad, M (2021). "Tissue-resident macrophages provide a pro-tumorigenic niche to early NSCLC cells". Nature. 595 (7868): 578–584. doi:10.1038/s41586-021-03651-8. PMC 8923521. PMID 34135508.
• Park, M; Aymeric, S; Ginhoux, F; Merad, M (2023). "Macrophages in health and disease". Cell. 185 (23): 4259–4279. doi:10.1016/j.cell.2022.10.007. PMC 9908006. PMID 36368305.

References

External links

• Merad Lab at the Icahn School of Medicine
• Lipschultz Precision Immunology Institute at the Icahn School of Medicine
• Department of Immunology and Immunotherapy at the Icahn School of Medicine