28 avril 2022: Pr Ido Amit

CMU - AUDITOIRE REnold (B01.2426)

Attendance in person for UNIGE/HUG members only
Présentiel réservé uniquement aux membres UNIGE/HUG

suivi d'un apéritif

Hôte: Pr Doron MERKLER,
Centre de recherche sur l'inflammation/Geneva Centre for inflammation &
Département de pathologie et immunologie/Department of Pathology and Immunology
Faculté de médecine UNIGE

prof. Ido Amit

Immunology Department
Weizmann Institute of Science, Rehovot, Israel


«Single-cell immunology:
past, present and future»

The immune system is a complex, dynamic and plastic ecosystem composed of various interacting cell types that are constantly sensing and responding to the tissue’s spatial and environmental cues. The immunology field, from very early on, invested great efforts and ingenuity to characterize the immune cell types and elucidate their function. However, accumulating evidence indicates that current technologies and classification schemes are limited in their ability to account for the functional heterogeneity of immune processes. Single cell genomics hold the potential to revolutionize the way we characterize complex immune assemblies and study their spatial organization, clonal distribution, dynamics, pathways and crosstalk. This emerging field of research can greatly affect basic and therapeutic research of the immune system. Prof. Amit is one of the major pioneers of the development of single cell genomics for characterizing the immune system and its interaction with the surrounding tissue/pathology and demonstrated the impact of these studies to understand the underlying cells, pathways, markers and molecules involved in a specific process or disease.

This emerging field of research can greatly affect basic tumour-immunology and development of novel immunotherapeutic targets. The Amit group is a hub of interdisciplinary technology development and we are convinced that the future challenges in our fields involve continuous integration of experimental and computational innovation leading toward simultaneous analysis of multiple regulatory layers on the single cell level.

Prof. Amit is a member of the organizing committee of the HCA and the European LifeTime flagship project, both aiming to characterize all cells in the human body in health and disease. Despite the tremendous improvement in immunotherapy treatment, current treatments are ineffective for most patients, even in metastatic melanoma for which immunotherapy is most successful - new treatment strategies are urgently needed. Based on our recent work and large collection of unpublished data on single cell analysis of melanoma, other solid tumour pre-and-post treatment we envision that our proposed research program will lead to a detailed and unprecedented high-resolution atlas of the responsive and unresponsive melanoma patient’s tumour cells, tumour microenvironment and metastatic niche. In this proposal, we will apply state-of-the-art single cell sequencing technologies, in order to map the different cancer, immune and stromal populations within the in vivo and ex vivo tumor microenvironment. We are confident that our proposal will make a great impact on novel development of effective biomarkers and immunotherapies. In this grant, Prof. Amit will lead the single cell genomics and bigdata analysis parts of the proposal.

Contributions to Science

1. Prof Amit pioneered the development of single cell genomics and its application for characterizing the immune system. The immunology field, from very early on, invested great efforts and ingenuity to characterize the cell types of immune system and elucidate their function and pathways. These discoveries were instrumental for our current understanding of both basic immunology and the development of life changing immunotherapies. Prof Amit pioneering development of single cell genomic technologies and the scientific breakthroughs from Prof. Amit lab to characterize the immune system using these technologies revolutionized our understanding of dozens of immune cell types and their roles in physiology and disease. These ground-breaking discoveries are dramatically impacting both basic immunology and the development of the next generation of immunotherapy. Indeed, single cell genomic technologies are already considered by many of the scientific leaders as the most important development of this decade. Prof. Amit was the first to develop and apply single cell genomics technologies towards elucidating the diversity of the immune system and demonstrated how his new technologies and vision can revolutionize the way we characterize complex immune assemblies, in both physiological and pathological contexts. In a seminal work published in Science on February 2014, Prof Amit was the first to demonstrate that single cell technologies can generate accurate and detailed cellular and molecular maps of all immune cells in a complete tissue without the need for cell-surface markers (Jaitin et al., 2014) ”Massively Parallel Single-Cell RNA-Seq for Marker-Free Decomposition of Tissues into Cell Types”. This revolutionary study, which was the first single cell tissue atlas has completely transformed immunology, hematopoiesis and many other areas in biology since. This publication was one of the drivers for the human cell atalas and other single cell mapping consortiums.

Selected publications:

a) Jaitin DA, Kenigsberg E, Keren-Shaul H, Elefant N, Paul F, Zaretsky I, Mildner A, Cohen N, Jung S, Tanay A, Amit I. Massively parallel single-cell RNA-seq for marker-free decomposition of tissues into cell types. Science, 2014 Feb 14:776-9.

b) Paul F, Arkin Y, Giladi A, Adhemar Jaitin D, Kenigsberg E, Keren-Shaul H, Winter D, Lara-Astiaso D, Gury M, Weiner A, David E, Cohen N, Kathrine-Bratt-Lauridsen F, Haas S, Schlitzer A Mildner A, Ginhoux F, Jung S, Trumpp A, Torben Porse B, Tanay A, Amit I.Transcriptional heterogeneity and lineage commitment in myeloid progenitors. Cell, 2015 Dec 14.

c) Ledergor G, Weiner A, Zada M, Wang SY, Cohen YC, Gatt ME, Snir N, Magen H, Koren-Michowitz M, Herzog-Tzarfati K, Keren-Shaul H, Bornstein C, Rotkopf R, Yofe I, David E, Yellapantula V, Kay S, Salai M, Ben Yehuda D, Nagler A, Shvidel L, Orr-Urtreger A, Halpern KB, Itzkovitz S, Landgren O, San-Miguel J, Paiva B, Keats JJ, Papaemmanuil E, Avivi I, Barbash GI, Tanay A, Amit I. Single cell dissection of plasma cell heterogeneity in symptomatic and asymptomatic myeloma. Nature Medicine. 2018 Dec;24(12):1867-1876.

d) Cohen M, Giladi A, Gorki AD, Solodkin DG, Zada M, Hladik A, Miklosi A, Salame TM, Halpern KB, David E, Itzkovitz S, Harkany T, Knapp S, Amit I. Lung Single-Cell Signaling Interaction Map Reveals Basophil Role in Macrophage Imprinting. Cell. 2018 Nov 1;175(4):1031-1044.

2. Ido continued research, and development of single cell genomics technologies, is transforming the way we understand the immune system and its role in diverse pathologies and is constantly discovering new immune cell-states, pathways and their functions in disease. His studies demonstrated that current technologies and classification schemes are limited in their ability to account for the functional heterogeneity of the immune system. His continuous effrts to develop new single cell technologies, demonstrated how single cell genomics can revolutionize the way we characterize complex immune assemblies and study their pathways, spatial organization, clonal distribution, dynamics, crosstalk, epigentics and function, in both physiological and pathological contexts. His technologies enabled to study novel immune pathways and define their spatial organization, dynamics, clonal distribution, function and crosstalk with other immune cell types and the resident tissue. The emerging single cell genomics field that Prof. Amit is one of its major pioneers, is already dramatically impacting basic and therapeutic research of the immune system in neurodegeneration and cancer.

Selected publications:

a) Jaitin DA, Weiner A, Lara-Astiaso D, Yofe I, Keren-Shaul H, David E, Tanay A, van Oudenaarden A and Amit I.Dissecting immune circuits by linking CRISPR pooled screens with single cell RNA-seq. Cell, 2016 Dec 15.

b) Medaglia C, Giladi A, Stoler-Barak L, De Giovanni M, Salame TM, Biram A, David E, Li H, Iannacone M, Shulman Z, Amit I. Science. Spatial reconstruction of immune niches by combining photoactivatable fluorescent reporter and single cell RNA-seq. Science 2017 Dec 22;358(6370):1622-1626. Microbiome Influences Prenatal and Adult Microglia in a Sex-Specific Manner.

c) Bost P, Giladi A, Liu Y, Bendjelal Y, Xu G, David E, Blecher-Gonen R, Cohen M, Medaglia C, Li H, Deczkowska A, Zhang S, Schwikowski B, Zhang Z, Amit I. Host-viral infection maps reveal signatures of severe COVID-19 patients. Cell. 2020 May 8.

d) Giladi A, Cohen M, Medaglia C, Baran Y, Li B, Zada M, Bost P, Blecher-Gonen R, Salame T, Mayer J, David E, Ronchese F, Tanay A, Amit I. PIC-seq characterizes cellular crosstalk by sorting and sequencing physically interacting cells. Nature Biotechnology 2020 Mar 9.

3. Ido leadership, vision and pioneering research around development and application of single cell genomic technologies are already revolutionising healthcare and are considered as the most important contribution to the field of molecular medicine of this decade. Functional heterogeneity of immune processes greatly limited progress in basic immunology research and its translation for molecular medicine and development of more effective immunotherapies. His research is changing the way we think about a wide range of immunological process and pathologies, from neurodegeneration to autoimmunity and cancer. I would like to mention three recent manuscripts, which exemplify the impact of Ido discoveries in molecular medicine. A major challenge in the field of cancer-immunology is to identify the different immune populations, pathways and checkpoints involved in regulation of immunity. In these three studies, Ido unique approach made a huge impact on our understanding of the role of various myeloid subtsets as well as a new and highly potent immune regulatory pathway, TREM2 in regulating the pathological immune microenvironment. These studies lead to better understanding of pathways and checkpoints controlling the immune compartment in the tumour microenviorment and may redirect the immuno-oncology field towards new immunotherapeutic strategies.

Selected publications:

a) Keren-Shaul H, Spinrad A, Weiner A, Matcovitch-Natan O, Dvir-Szternfeld R, Ulland TK, David E, Baruch K, Lara-Astaiso D, Toth B, Itzkovitz S, Colonna M, Schwartz M, Amit I. A Unique Microglia Type Associated with Restricting Development of Alzheimer's Disease. Cell. 2017 Jun 15.

b) Jaitin AD, Adlung L, Thaiss CA, Weiner A, Li B, Descamps H, Lundgren P, Bleriot C, Liu Z, Deczkowska A, Keren-Shaul H, David E, Zmora N, Eldar SM, Lubezky N, Shibolet O, Hill DA, Lazar MA, Colonna M, Ginhoux F, Shapiro H, Elinav E, Amit I. Lipid-associated macrophages control metabolic homeostasis in a Trem2-dependent manner. Cell. 2019 Jul 25;178(3):686-698.

c) Li H, van der Leun A, Yofe I, Lubling Y, Gelbard Solodkin D, van Akkooi A, van den Braber M, Rozeman L, Haanen J, Blank C, Horlings H, David E, Baran Y, Berkovitz A, Lifshitz A, Schumacher T, Tanay A, Amit I. Dysfunctional CD8+ T cells form a proliferative, dynamically regulated compartment within human melanoma. Cell 2019 Feb 7;176(4):775-789.

d) Katzenelenbogen Y, Sheban F, Yalin A, Yofe I, Svetlichnyy D,  Adhemar Jaitin D, Bornstein C, Moshe A, Keren-Shaul H, Cohen M, Wang S, Li B, David E, Salame T, Weiner A, Amit I Coupled scRNA-Seq and Intracellular Protein Activity Reveal an Immunosuppressive Role of TREM2 in Cancer. Cell 2020 Aug 20;182(4):872-885

All publications can be found  here >> 

Selected awards & Honors

  • Recipient of the Landau Prize (2021)
  • Recipient of the Bruno award (2020)
  • Recipient of the Sanofi Institute Pasture award (2019)
  • Recipient of a Consolidator award by the European Research Council (2018)
  • HHMI International Research Scholars award (2017)
  • Helen and Martin Kimmel award for innovative investigation (2016)
  • Rappaport Prize for Excellence in Biomedical Research (2016)
  • EMBO Gold Medal award (2015)
  • Morris L. Levinson Prize in Biology from the Weizmann Institute's Scientific Council (2015)
  • Ernest and Bonnie Beutler Research Program of Excellence in Genomic Medicine (2015)
  • Krill Prize for Excellence in Scientific Research (2015)
  • EMBO Young Investigator Award (2013)
  • Yigal Alon Foundation Scholar – Program for distinguished junior faculty in Israel (2012)
  • Recipient of a Starting Scientist Award by the European Research Council (2012)
  • HFSP Career Development Award (2011)
  • Claire and Emanuel G. Rosenblatt Fellowship Award (2009)                                                           
  • HFSP Long Term Fellowship (2008)
  • J. F. Kennedy award for Ph.D research (2007)
28 avr. 2022

Frontiers in biomedicine