Miriam Merad

Last updated
Miriam Merad
Born
Paris, France
Education
Scientific career
Fields
Institutions Icahn School of Medicine at Mount Sinai

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]

Contents

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.

In April 2024, Merad was named as the new Dean for Translational Research and Therapeutic Innovation for the Ican 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. [20] 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. [21] 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, [22] the characterization of mature dendritic cells enriched in immunoregulatory molecules (mregDCs) that limit responses to immune checkpoint blockade, [23] and the niches in tumors in which mregDCs operate. [24]

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, [25] how Long COVID can be classified, [26] the importance of immigrants to science in the US [27] and written about her experiences as a mother and a scientist. [28]

Honors

Notable publications

Related Research Articles

<span class="mw-page-title-main">Dendritic cell</span> Accessory cell of the mammalian immune system

A dendritic cell (DC) is an antigen-presenting cell of the mammalian immune system. A DC's main function is to process antigen material and present it on the cell surface to the T cells of the immune system. They act as messengers between the innate and adaptive immune systems.

<span class="mw-page-title-main">Macrophage</span> Type of white blood cell

Macrophages are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris, and foreign substances, which do not have proteins that are specific to healthy body cells on their surface. This process is called phagocytosis, which acts to defend the host against infection and injury.

Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as activation immunotherapies, while immunotherapies that reduce or suppress are classified as suppression immunotherapies. Immunotherapy is under preliminary research for its potential to treat various forms of cancer.

<span class="mw-page-title-main">Langerhans cell</span> Cell type

A Langerhans cell (LC) is a tissue-resident macrophage of the skin once thought to be a resident dendritic cell. These cells contain organelles called Birbeck granules. They are present in all layers of the epidermis and are most prominent in the stratum spinosum. They also occur in the papillary dermis, particularly around blood vessels, as well as in the mucosa of the mouth, foreskin, and vaginal epithelium. They can be found in other tissues, such as lymph nodes, particularly in association with the condition Langerhans cell histiocytosis (LCH).

<span class="mw-page-title-main">Cancer immunotherapy</span> Artificial stimulation of the immune system to treat cancer

Cancer immunotherapy (immuno-oncotherapy) is the stimulation of the immune system to treat cancer, improving the immune system's natural ability to fight the disease. It is an application of the fundamental research of cancer immunology (immuno-oncology) and a growing subspecialty of oncology.

<span class="mw-page-title-main">Antigen-presenting cell</span> Cell that displays antigen bound by MHC proteins on its surface

An antigen-presenting cell (APC) or accessory cell is a cell that displays an antigen bound by major histocompatibility complex (MHC) proteins on its surface; this process is known as antigen presentation. T cells may recognize these complexes using their T cell receptors (TCRs). APCs process antigens and present them to T cells.

Cross-presentation is the ability of certain professional antigen-presenting cells (mostly dendritic cells) to take up, process and present extracellular antigens with MHC class I molecules to CD8 T cells (cytotoxic T cells). Cross-priming, the result of this process, describes the stimulation of naive cytotoxic CD8+ T cells into activated cytotoxic CD8+ T cells. This process is necessary for immunity against most tumors and against viruses that infect dendritic cells and sabotage their presentation of virus antigens. Cross presentation is also required for the induction of cytotoxic immunity by vaccination with protein antigens, for example, tumour vaccination.

<span class="mw-page-title-main">CD40 (protein)</span> Mammalian protein found in humans

Cluster of differentiation 40, CD40 is a type I transmembrane protein found on antigen-presenting cells and is required for their activation. The binding of CD154 (CD40L) on TH cells to CD40 activates antigen presenting cells and induces a variety of downstream effects.

Malignant histiocytosis is a rare hereditary disease found in the Bernese Mountain Dog and humans, characterized by histiocytic infiltration of the lungs and lymph nodes. The liver, spleen, and central nervous system can also be affected. Histiocytes are a component of the immune system that proliferate abnormally in this disease. In addition to its importance in veterinary medicine, the condition is also important in human pathology.

<span class="mw-page-title-main">Histiocytoma (dog)</span> Benign tumor in dogs

A histiocytoma in the dog is a benign tumor. It is an abnormal growth in the skin of histiocytes (histiocytosis), a cell that is part of the immune system. A similar disease in humans, Hashimoto-Pritzker disease, is also a Langerhans cell histiocytosis. Dog breeds that may be more at risk for this tumor include Bulldogs, American Pit Bull Terriers, American Staffordshire Terriers, Scottish Terriers, Greyhounds, Boxers, and Boston Terriers. They also rarely occur in goats and cattle.

<span class="mw-page-title-main">Cancer immunology</span> Study of the role of the immune system in cancer

Cancer immunology (immuno-oncology) is an interdisciplinary branch of biology and a sub-discipline of immunology that is concerned with understanding the role of the immune system in the progression and development of cancer; the most well known application is cancer immunotherapy, which utilises the immune system as a treatment for cancer. Cancer immunosurveillance and immunoediting are based on protection against development of tumors in animal systems and (ii) identification of targets for immune recognition of human cancer.

<span class="mw-page-title-main">PD-L1</span> Mammalian protein found in humans

Programmed death-ligand 1 (PD-L1) also known as cluster of differentiation 274 (CD274) or B7 homolog 1 (B7-H1) is a protein that in humans is encoded by the CD274 gene.

The following outline is provided as an overview of and topical guide to immunology:

The Icahn Genomics Institute is a biomedical and genomics research institute within the Icahn School of Medicine at Mount Sinai in New York City. Its aim is to establish a new generation of medicines that can better treat diseases afflicting the world, including cancer, heart disease and infectious pathogens. To do this, the institute’s doctors and scientists are developing and employing new types of treatments that utilize DNA and RNA based therapies, such as CRISPR, siRNA, RNA vaccines, and CAR T cells, and searching for novel drug targets through the use of functional genomics and data science. The institute is led by Brian Brown, a leading expert in gene therapy, genetic engineering, and molecular immunology.

The dendritic cell-based cancer vaccine is an innovation in therapeutic strategy for cancer patients.

<span class="mw-page-title-main">Mikael Pittet</span> Swiss research scientist

Mikaël Pittet is a Swiss research scientist.

Melanie Greter is a Swiss neuroimmunologist and a Swiss National Science Foundation Professor in the Institute of Experimental Immunology at the University of Zurich. Greter explores the ontogeny and function of microglia and border-associated macrophages of the central nervous system to understand how they maintain homeostasis and contribute to brain-related diseases.

<span class="mw-page-title-main">Michele De Palma</span> Italian biologist

Michele 'Miki' De Palma is an Italian biologist and a professor at EPFL. He is known for his work on the role of macrophages in cancer progression and the discovery of Tie2-expressing angiogenic monocytes.

<span class="mw-page-title-main">Gwendalyn J. Randolph</span> American immunologist

Gwendalyn J. Randolph is an American immunologist, the Emil R. Unanue Distinguished Professor in the Department of Immunology and Pathology at Washington University School of Medicine where she is currently co-director of the Immunology Graduate Program. During her postdoctoral work, Randolph characterized monocyte differentiation to dendritic cells and macrophages and made advances in our understanding of dendritic cell trafficking and the fate of monocytes recruited to sites of inflammation. Her lab has contributed to the Immunological Genome Project by characterizing macrophage gene expression. Her work now focuses on the immunological mechanisms driving atherosclerosis and inflammatory bowel disease (IBD) by exploring lymphatic function and lipoprotein trafficking.

<span class="mw-page-title-main">Dermal macrophage</span> Skin macrophages used for wound repair and hair growth

Dermal macrophages are macrophages in the skin that facilitate skin homeostasis by mediating wound repair, hair growth, and salt balance. Their functional role in these processes is the mediator of inflammation. They can acquire an M1 or M2 phenotype to promote or suppress an inflammatory response, thereby influencing other cells' activity via the production of pro-inflammatory or anti-inflammatory cytokines. Dermal macrophages' ability to acquire pro-inflammatory properties also potentiates them in cancer defence. M1 macrophages can suppress tumour growth in the skin by their pro-inflammatory properties. However, M2 macrophages support tumour growth and invasion by the production of Th2 cytokines such as TGFβ and IL-10. Thus, the exact contribution of each phenotype to cancer defence and the skin's homeostasis is still unclear.

References

  1. ↑ "Cancer Vaxxer: A Profile of Miriam Merad". the-scientist.com. Retrieved 31 May 2019.
  2. ↑ "Three Scientists to Receive Top Honors from the Cancer Research Institute for Outstanding Contributions to Cancer Immunology and Immunotherapy". cancerresearch.org. Cancer Research Institute. Retrieved 31 May 2019.
  3. ↑ "2020 NAS Election". www.nasonline.org. Retrieved 28 April 2020.
  4. ↑ "National Academy of Medicine Elects 100 New Members". www.nam.edu/. Retrieved 11 October 2023.
  5. ↑ "miriam-merad, MD, PhD". icahn.mssm.edu. Retrieved 3 June 2019.
  6. ↑ "Engleman Trainees 1983-present" (PDF). Retrieved 3 June 2019.
  7. ↑ "Irving L. Weissman, MD" . Retrieved 6 Dec 2022.
  8. ↑ "miriam-merad, MD/PhD". icahn.mssm.edu. Retrieved 3 June 2019.
  9. ↑ "Human Immune Monitoring Center". www.mountsinai.org/. Retrieved 15 Dec 2022.
  10. ↑ "Microbiome Translational Center". www.mountsinai.org/. Retrieved 15 Dec 2022.
  11. ↑ "Center for Inborn Errors of Immunity". www.mountsinai.org/. Retrieved 15 Dec 2022.
  12. ↑ "Finding Common Cause to Advance Immunotherapy Access with Novel Programs". www.mountsinai.org/. Retrieved 15 Dec 2022.
  13. ↑ "The Tisch Cancer Institute and Precision Immunology Institute at Mount Sinai Launch Center for Computational Immunology". www.mountsinai.org/. Retrieved 15 Dec 2022.
  14. ↑ "Icahn School of Medicine at Mount Sinai Names Miriam Merad, MD, PhD, as Dean for Translational Research and Therapeutic Innovation". www.newswise.com. Retrieved 2024-04-30.
  15. ↑ "Tissue-Resident Macrophages Self-Maintain Locally throughout Adult Life with Minimal Contribution from Circulating Monocytes". www.sciencedirect.com/journal/immunity. Retrieved 11 May 2022.
  16. ↑ Ginhoux, Florent; Greter, Melanie; Leboeuf, Marylene; Nandi, Sayan; See, Peter; Gokhan, Solen; Mehler, Mark F.; Conway, Simon J.; Ng, Lai Guan; Stanley, E. Richard; Samokhvalov, Igor M.; Merad, Miriam (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.
  17. ↑ "Blood-derived dermal langerin+ dendritic cells survey the skin in the steady state". www.rupress.org/jem. Retrieved 11 May 2022.
  18. ↑ "BRAFV600E-induced senescence drives Langerhans cell histiocytosis pathophysiology". www.nature.com/nm/. Retrieved 15 September 2023.
  19. ↑ "A shift in lung macrophage composition is associated with COVID-19 severity and recovery". www.science.org/journal/stm. Retrieved 15 September 2023.
  20. ↑ "Cancer Vaxxer: A Profile of Miriam Merad". the-scientist.com. Retrieved 31 May 2019.
  21. ↑ "Tissue-resident macrophages provide a pro-tumorigenic niche to early NSCLC cells". www.nature.com/. Retrieved 15 September 2023.
  22. ↑ "TREM2 macrophages drive NK cell paucity and dysfunction in lung cancer". www.nature.com/ni/. Retrieved 15 September 2023.
  23. ↑ "A conserved dendritic-cell regulatory program limits antitumour immunity". www.nature.com//. Retrieved 15 September 2023.
  24. ↑ "Intratumoral dendritic cell–CD4+ T helper cell niches enable CD8+ T cell differentiation following PD-1 blockade in hepatocellular carcinoma". www.nature.com/nm/. Retrieved 15 September 2023.
  25. ↑ "Neoadjuvant clinical trials provide a window of opportunity for cancer drug discovery". www.nature.com/nm/. Retrieved 12 May 2022.
  26. ↑ "Pathological sequelae of long-haul COVID". www.nature.com/ni/. Retrieved 12 May 2022.
  27. ↑ ""America First" Will Destroy U.S. Science". www.sciencedirect.com/journal/cell. Retrieved 12 May 2022.
  28. ↑ "Reflections from a mother scientist". www.nature.com/nm/. Retrieved 12 May 2022.
  29. ↑ "About the Academy of Immuno-Oncology" . Retrieved 15 September 2023.
  30. ↑ "International Union of Immunological Societies" . Retrieved 20 February 2020.
  31. ↑ "The American Society for Clinical Investigation" . Retrieved 3 June 2019.
  32. ↑ "Three Scientists to Receive Top Honors from the Cancer Research Institute for Outstanding Contributions to Cancer Immunology and Immunotherapy". cancerresearch.org. Cancer Research Institute. Retrieved 31 May 2019.
  33. ↑ "Miriam Merad". www.nasonline.org/. Retrieved 12 May 2022.
  34. ↑ "Highly Cited Researchers". www.clarivate.com/. Retrieved 6 May 2022.
  35. ↑ "Miriam Merad". Carnegie Corporation of New York. Retrieved June 25, 2024.
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