Biography

Current Position

Full Professor, Molecular & Cell Biology Department, Weizmann Institute, Israel The Knell Family Professorial Chair

Education

INSTITUTION AND LOCATION DEGREE
(if applicable)

Completion Date
MM/YYYY

 FIELD OF  STUDY
Cambridge University, Cambridge, UK B.Sc. 06/1993 Natural Sciences, Pathology
Hebrew University of Jerusalem, Israel M.Sc. 01/1997 Immunology and Cancer Research
Imperial College, London, UK Ph.D. 09/2002 Cancer Research
Johns Hopkins University School of Medicine Postdoctoral 11/2006 Cancer Genetics

A. Personal Statement

I have a long-standing interest in the molecular genetics of cancer. As a postdoctoral fellow in Bert Vogelstein’s lab, I was the first to uncover the high frequency of mutations in the PIK3CA gene in human cancers (Science, 2004) and made important contributions to the characterization of their effects (Cancer Cell 2005). My laboratory’s focus involves the identification and characterization of gene mutations that play a role in the progression of cutaneous melanoma. Our aim is to delineate ideal protein target combinations in melanoma to achieve lasting disease control. We have identified and characterized multiple melanoma mutations over the years and have emphasized their comprehensive functional analysis. My lab was the first to demonstrated that, contrary to previous beliefs, metalloproteinases may function as tumour suppressors rather than oncogenes (Nat Gen 2009), identified ERBB4 is the most highly mutated tyrosine kinase in melanoma (Nat Gen 2009), paving the way to a phase II clinical trial (NCT01264081) and was the first to publish the melanoma whole exome (Nat Gen 2011). My lab was part of the TCGA workgroup who published the most comprehensive Genomic Classification of Cutaneous Melanoma (Cell, 2015). Recently, using unbiased analyses to identify novel tumour suppressor genes my lab discovered RASA2 as a novel melanoma tumor suppressor (Nat Gen 2015). Recently, my lab moved into the immunogenomic field and developed novel methods to identify melanoma neo-antigens using genetic and rapid proteomic methods (Cancer Discovery 2018). We have further set up the first mouse model that aims to tease apart the influences of tumor heterogeneity vs. mutational load on anti-tumor immunity. Our findings in mice and human patients suggest that the strongest genetic determinant affecting the anti-tumor immune response is tumor heterogeneity (Cell 2019). The combination of these technologies, models and experience fulfill a strong foundation for the submitted proposal.

  1. Samuels Y, Wang Z, Bardelli A, Silliman N, Ptak J, Szabo S, Yan H, Gazdar A, Powell SM, Riggins GJ, Willson JK, Markowitz S, Kinzler KW, Vogelstein B, Velculescu VE: High frequency of mutations of the PIK3CA gene in human cancers. Science 2004, 304:554. Impact factor: 34.6; Citations 2,478.
  2. Wei X, Walia V, Lin JC, Teer JK, Prickett TD, Gartner J, Davis S, Stemke-Hale K, Davies MA, Gershenwald JE, Robinson W, Robinson S, Rosenberg SA, Samuels Y: Exome sequencing identifies GRIN2A as frequently mutated in melanoma. Nat Genet 2011, 43:442-446. Impact factor: 31.6; Citations 328.
  3. Kalaora, S., Wolf, Y., Feferman, T., Barnea, E., Greenstein, E., Reshef, D., Tirosh, I., Reuben, A., Patkar, S., Levy, R., Quinkhardt, J., Omokoko, T., Qutob, N., Golani, O., Zhang, J., Mao, X., Song, X., Bernatchez, C., Haymaker, C., Forget, M. A., Creasy, C., Greenberg, P., Carter, B. W., Cooper, Z. A., Rosenberg, S. A., Lotem, M., Sahin, U., Shakhar, G., Ruppin, E., Wargo, J. A., Friedman, N., Admon, A. & Samuels, Y. Combined Analysis of Antigen Presentation and T-cell Recognition Reveals Restricted Immune Responses in Melanoma. Cancer Discov 8, 1366-1375, doi:10.1158/2159-8290.CD-17-1418 (2018). Impact factor: 24.3; Citations 23.
  4. Wolf, Y., Bartok, O., Patkar, S., Eli, G. B., Cohen, S., Litchfield, K., Levy, R., Jimenez-Sanchez, A., Trabish, S., Lee, J. S., Karathia, H., Barnea, E., Day, C. P., Cinnamon, E., Stein, I., Solomon, A., Bitton, L., Perez-Guijarro, E., Dubovik, T., Shen-Orr, S. S., Miller, M. L., Merlino, G., Levin, Y., Pikarsky, E., Eisenbach, L., Admon, A., Swanton, C., Ruppin, E. & Samuels, Y. UVB-Induced Tumor Heterogeneity Diminishes Immune Response in Melanoma. Cell 179, 219-235 e221, doi:10.1016/j.cell.2019.08.032 (2019). Impact factor: 36.2; Citations 39.

B. Positions and Honors

Positions and Employment

1998-1999
Senior Research Assistant, Intelligene, Jerusalem, Israel

1999-2003
Ludwig Institute for Cancer Research, Imperial College, London, UK

2006-2013
Investigator (Tenure-Track Assistant Professor), National Institutes of Health, Bethesda, MD

2013-present
Knell Family Professor

2013-2021
Associate Professor (Tenured), Weizmann Institute of Science, Rehovot, Israel

2015-present
Director of the Ekard Institute for Cancer Diagnosis Research of the Moross Integrated Cancer Center

2015-present
Director of the Weizmann-Brazil Tumor Bank of the Moross Integrated Cancer Center

2021-present  
Full Professor at the Dept. of Molecular and Cell Biology, Weizmann Institute of Science, Israel

2022        
EACR President Elect

Other Experience and Professional Memberships

2010
Member of the Scientific Program Committee, AACR Annual Meeting 2011

2011-2013
Member, Earl Stadtman Investigator Search Committee

2011-present
Panel of Expert Advisers for the Nature Index

2012-present
Member, The Cancer Genome Atlas (TCGA) Melanoma Tumor Working Group

2012
Member of the Scientific Program Committee, AACR Annual Meeting 2013

2012
Member of the Education Committee, AACR Annual Meeting 2013 NIH Peer Review Committee: Tumor Cell Biology Study Section Ad Hoc Reviewer

2012
The Welcome Trust, Scientific Review Panel

2012-present
Editorial Board Member, Pigment Cell and Melanoma Research

2012-2015
Editorial Board Member, Journal of Investigative Dermatology

2013
Reviewer, Israel Cancer Association

2013
Reviewer, Israel Science Foundation

2014
Member of the Weizmann Appointments and Promotion Committee (V9)

2015
Co-organizer, 2nd EACR Conference “Genomics: Cancer Evolution and Diversity”

2016-present
Elected Member to the EACR Board

2016-2017
Scientific Committee member ESMO –EACR annual congress, Madrid, Spain

2016-2017
Scientific Committee member Broad-ISF Fourth Cell Circuits Symposium, Boston, MA, USA

2016-2017
Co-organizer, 3rd EACR Special Conference on Cancer Genomics, 2017, Cambridge UK

2016-2017
Scientific Program Committee member, AACR Annual Meeting 2017

2014-2017
Member of the Weizmann Appointments and Promotion Committee (V9)

2014-2017
Member of the Life Sciences Faculties Appointments and Promotion Committee (LSV9)

2017-2018
Scientific Committee member Broad-ISF Fifth Cell Circuits Symposium, Jerusalem, Israel

2017-2018
Scientific Committee member for the ESMO 2018 Congress

2018-2019
Co-organizer, 4th EACR special conference on Cancer Genomics

2019
Scientific committee member for the ESMO congress

2020
Scientific committee member for the ESMO congress

2020
Cancer, immunology and physiology scientific advisory committee, ILANIT (FISEB)

Honors

2003
European Molecular Biology Organization Postdoctoral Fellowship

2006
Alfred Blalock, Young Investigators' Day award, Johns Hopkins School of Medicine

2006
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Research day award

2008
NIH Directors Challenge Innovation Award

2008
NIH Bench-to-Bedside Award

2008
The Harry J. Lloyd Charitable Trust Award

2009
Genome Technology top 25 Young Investigator award

2011
Pigment Cell and Melanoma Research prize

2013
Peter and Patricia Gruber Prize for Scientific Excellence

2013
Knell Family Professorial Chair;

2014
TEVA-Israel Science Foundation Founders Prize

2016
Pezcoller Foundation-EACR Cancer Researcher Award

2016
Youdim Family Prize for Excellence in Cancer Research

2019
Nominated to the European Academy of Cancer Sciences

2020

Elected member of EMBO

2020

Estela Medrano Memorial Award

2021  
                    
The Michael Bruno Memorial Award

C. Contributions to Science

  1. We discovered that, contrary to previous beliefs, metalloproteinases may function as tumour suppressors rather than oncogenes. These results helped explain why clinical trials with metalloproteinase inhibitors yielded negative results. We further identified additional metalloproteinases, namely ADAMTSs and ADAMs as drivers in melanoma.
    • Palavalli LH, Prickett TD, Wunderlich JR, Wei X, Burrell AS, Porter-Gill P, Davis S, Wang C, Cronin JC, Agrawal NS, Lin JC, Westbroek W, Hoogstraten-Miller S, Molinolo AA, Fetsch P, Filie AC, O'Connell MP, Banister CE, Howard JD, Buckhaults P, Weeraratna AT, Brody LC, Rosenberg SA, Samuels Y: Analysis of the matrix metalloproteinase family reveals that MMP8 is often mutated in melanoma. Nat Genet 2009, 41:518-520. Impact factor: 31.6; Citations 103.
    • Lopez-Otin, C., L.H. Palavalli, and Y. Samuels, Protective roles of matrix metalloproteinases: from mouse models to human cancer. Cell Cycle, 2009. 8(22): p. 3657-62. Impact factor: 3.9; Citations 75.
    • Wei, X., T.D. Prickett, C.G. Viloria, A. Molinolo, J.C. Lin, I. Cardenas-Navia, P. Cruz, N.C.S. Program, S.A. Rosenberg, M.A. Davies, J.E. Gershenwald, C. Lopez-Otin, and Y. Samuels, Mutational and functional analysis reveals ADAMTS18 metalloproteinase as a novel driver in melanoma. Mol Cancer Res, 2010. 8(11): p. 1513-25. (Highlighted in Mol Cancer Res). Impact factor: 4.5; Citations 31.
    • Wei, X., A. Moncada-Pazos, S. Cal, C. Soria-Valles, J. Gartner, U. Rudloff, J.C. Lin, N.C.S. Program, S.A. Rosenberg, C. Lopez-Otin, and Y. Samuels, Analysis of the disintegrin-metalloproteinases family reveals ADAM29 and ADAM7 are often mutated in melanoma. Hum Mutat, 2011. 32(6): p. E2148-75. Impact factor: 5; Citations 28.
  2. We discovered two novel melanoma oncogenes GRM3 and ERBB4. We found ERBB4 to be the most highly mutated tyrosine kinase in melanoma and that treatment with the pan-ERBB inhibitor, lapatinib, suppressed the proliferation of ERBB4 mutant melanoma cells. This study paved the way to establishing a clinical trial using lapatinib in melanoma patients harboring ERBB4 mutations. Patients for this clinical trial were recruited from two different sites; NCI and Memorial Sloan Kettering Cancer Center.
    • Prickett TD, Agrawal NS, Wei X, Yates KE, Lin JC, Wunderlich JR, Cronin JC, Cruz P, Rosenberg SA, Samuels Y: Analysis of the tyrosine kinome in melanoma reveals recurrent mutations in ERBB4. Nat Genet 2009, 41:1127-1132. Impact factor: 31.6; Citations 235.
    • Prickett, T.D., X. Wei, I. Cardenas-Navia, J.K. Teer, J.C. Lin, V. Walia, J. Gartner, J. Jiang, P.F. Cherukuri, A. Molinolo, M.A. Davies, J.E. Gershenwald, K. Stemke-Hale, S.A. Rosenberg, E.H. Margulies, and Y. Samuels, Exon capture analysis of G protein-coupled receptors identifies activating mutations in GRM3 in melanoma. Nature Genetics, 2011. 43(11): p. 1119-26. Highlighted in Cancer Discovery and in Pigment Cell Melanoma Res. Impact factor: 31.6; Citations 98.
    • Lau, C., K.J. Killian, Y. Samuels, and U. Rudloff, ERBB4 mutation analysis: emerging molecular target for melanoma treatment. Methods Mol Biol, 2014. 1102: p. 461-80. Impact factor: 1.2; Citations 12.
    • clinicaltrials.gov NCT01264081; PI: Rudloff, Associate Investigator: Samuels.
  3. We were the first to perform whole exome sequencing of melanoma patients and were the first to reveal that melanoma is one of the most highly mutated solid cancers. Our whole exomes further identified the novel tumor suppressors GRIN2A and RASA2.
    • Wei X, Walia V, Lin JC, Teer JK, Prickett TD, Gartner J, Davis S, Stemke-Hale K, Davies MA, Gershenwald JE, Robinson W, Robinson S, Rosenberg SA, Samuels Y: Exome sequencing identifies GRIN2A as frequently mutated in melanoma. Nat Genet 2011, 43:442-446. Impact factor: 31.6; Citations 328.
    • Prickett, T.D., B.J. Zerlanko, V.K. Hill, J.J. Gartner, N. Qutob, J. Jiang, M. Simaan, J. Wunderlich, J.S. Gutkind, S.A. Rosenberg, and Y. Samuels, Somatic Mutation of GRIN2A in Malignant Melanoma Results in Loss of Tumor Suppressor Activity via Aberrant NMDAR Complex Formation. J Invest Dermatol, 2014. 134(9): p. 2390-8. Impact factor: 7.2; Citations 16.
    • Arafeh, R., N. Qutob, R. Emmanuel, A. Keren-Paz, J. Madore, A. Elkahloun, J.S. Wilmott, J.J. Gartner, A. Di Pizio, S. Winograd-Katz, S. Sindiri, R. Rotkopf, K. Dutton-Regester, P. Johansson, A.L. Pritchard, N. Waddell, V.K. Hill, J.C. Lin, Y. Hevroni, S.A. Rosenberg, J. Khan, S. Ben-Dor, M.Y. Niv, I. Ulitsky, G.J. Mann, R.A. Scolyer, N.K. Hayward, and Y. Samuels, Recurrent inactivating RASA2 mutations in melanoma. Nature Genetics, 47, 1408-10 2015. Impact factor: 31.6; Citations 48.
  4. We were the first to identify a functional recurrent synonymous mutation in melanoma, an alteration which is rarely investigated in the cancer genomics field. This was the first study indicating that “silent” alterations have a role to play in human cancer, emphasizing the importance of their investigation in future cancer genome studies.
    • Gartner, J.J., S.C. Parker, T.D. Prickett, K. Dutton-Regester, M.L. Stitzel, J.C. Lin, S. Davis, V.L. Simhadri, S. Jha, N. Katagiri, V. Gotea, J.K. Teer, X. Wei, M.A. Morken, L.L. Elnitski, M.A. Davies, J.E. Gershenwald, H. Carter, R. Karchin, W. Robinson, S. Robinson, S.A. Rosenberg, F.S. Collins, G. Parmigiani, A.A. Komar, C. Kimchi-Sarfaty, N.K. Hayward, E.H. Margulies, and Y. Samuels, Whole-genome sequencing identifies a recurrent functional synonymous mutation in melanoma. Proc Natl Acad Sci U S A, 2013. 110(33): p. 13481-6. Highlighted in Research Watch in Cancer Discovery. Impact factor: 9.4; Citations 105.
    • Gotea, V., J.J. Gartner, N. Qutob, L. Elnitski, and Y. Samuels, The functional relevance of somatic synonymous mutations in melanoma and other cancers. Pigment Cell Melanoma Res, 2015. Impact factor: 4.1; Citations 24.
    • Soussi, T., P.E. Taschner, and Y. Samuels, Synonymous Somatic Variants in Human Cancer Are Not Infamous: A Plea For Full Disclosure in Databases And Publications. Hum Mutat, 2016. Impact factor: 5. Citations 12.
  5. Together with the Rosenberg group, we were the first to mine exomic sequencing data to identify mutated antigens recognized by adoptively transferred tumor-reactive T cells, opening the way to numerous more studies proving that neo-antigens derived from somatic mutations are the target of the immune system. In order to identify neo-antigens that are selectively recognized by tumour infiltrating lymphocytes the lab has developed the analysis of the mutated HLA-class I peptidome of human melanoma tumour cells using a novel strategy combining whole-exome sequencing and mass spectrometry analysis. As the technology is unbiased and accurate it may be used clinically in the future as a potential diagnostic strategy for personalized immunotherapy, not only for melanoma patients but a variety of additional tumour types. The lab has also set up the first mouse model that aims to tease apart the influences of tumor heterogeneity vs. mutational load on anti-tumor immunity. Showing that tumor heterogeneity is a strong genetic determinant affecting the anti-tumor immune response.
    • Robbins, P.F., Y.C. Lu, M. El-Gamil, Y.F. Li, C. Gross, J. Gartner, J.C. Lin, J.K. Teer, P. Cliften, E. Tycksen, Y. Samuels, and S.A. Rosenberg, Mining exomic sequencing data to identify mutated antigens recognized by adoptively transferred tumor-reactive T cells. Nature Medicine, 2013. 19(6): p. 747-52. Impact factor: 27.3; Citations 616.
    • Lu, Y.C., X. Yao, J.S. Crystal, Y.F. Li, M. El-Gamil, C. Gross, L. Davis, M.E. Dudley, J.C. Yang, Y. Samuels, S.A. Rosenberg, and P.F. Robbins, Efficient identification of mutated cancer antigens recognized by T cells associated with durable tumor regressions. Clin Cancer Res, 2014. 20(13): p. 3401-10. Impact factor: 8.7; Citations 204.
    • Kalaora, S., Wolf, Y., Feferman, T., Barnea, E., Greenstein, E., Reshef, D., Tirosh, I., Reuben, A., Patkar, S., Levy, R., Rosenberg, S. A., Lotem, M., Sahin, U., Shakhar, G., Ruppin, E., Wargo, J. A., Friedman, N., Admon, A. & Samuels, Y. Combined Analysis of Antigen Presentation and T-cell Recognition Reveals Restricted Immune Responses in Melanoma. Cancer Discov 8, 1366-1375, doi:10.1158/2159-8290.CD-17-1418 (2018). Impact factor: 24.3 ; Citations 23.
    • Wolf, Y., Bartok, O., Patkar, S., Eli, G. B., Cohen, S., Litchfield, K., Levy, R., Jimenez-Sanchez, A., Trabish, S., Lee, J. S., Karathia, H., Miller, M. L., Merlino, G., Levin, Y., Pikarsky, E., Eisenbach, L., Admon, A., Swanton, C., Ruppin, E. & Samuels, Y. UVB-Induced Tumor Heterogeneity Diminishes Immune Response in Melanoma. Cell 179, 219-235 e221, doi:10.1016/j.cell.2019.08.032 (2019). Impact factor: 36.2; Citations 39.

    • Osnat Bartok, Abhijeet Pataskar, Remco Nagel, Ronen Levy, Eden Goldfarb, Pierre-Rene Körner, Inger Z M Kreuger, Julien Champagne, Esther Zaal, Onno B. Bleijerveld, Xinyao Huang, Juliana Kenski, Jennifer Wargo, Alexander Brandis, Yishai Levin, Orel Mizrahi, Noam Stern-Ginossar, Daniel S Peeper, Maarten Altelaar, Celia Berkers, Yardena Samuels*, Reuven Agami*. Anti-tumor immunity induces the presentation of aberrant peptides in melanoma. Nature doi: 10.1038/s41586-020-03054-1 (2020).

    • Shelly Kalaora, Adi Nagler, Deborah Gitta Rosenberg, Michal Alon, Eilon Barnea, Ronen Levy, Kevin Vervier, Ron Rotkopf, Sophie Trabish, Tali Dadosh, Smadar Levin-Zaidman, Leore Geller, Eden Goldfarb, Polina Greenberg, Neerupma Bhardwaj, Alexandre Reuben, Reetakshi Arora, Michal Lotem, Arie Admon, Yishai Levin, Trevor D. Lawley, David Adams, Naama Geva-Zatorsky, Jennifer Wargo, Ravid Straussman, Yardena Samuels.. Identification of microbial-derived HLA-bound peptides in melanoma. Nature (Accepted).
    • Aviyah Peri, Erez Greenstein, Tamir Dingjan, Shlomit Reich-Zeliger, Michal Alo, Eilon Barnea, Ronen Levy, Shelly Kalaora, Bareket Dassa, Ester Feldmesser, Polina Greenberg, Yishai Levin, Mitch Levesque, Michal Lotem, Arie Admon, Steven Rosenberg, Masha Y. Niv, Nir Friedman, Yardena Samuels. Combined presentation and immunogenicity analysis reveals a recurrent RAS.Q61K neoantigen in melanoma. Journal of Clinical Investigation 2021. 131, doi:10.1172/JCI129466. 
    • Shelly Kalaora, Adi Nagler, Jennifer A. Wargo, Yardena Samuels. Mechanisms of immune activation and regulation: lessons from melanoma. Nature Reviews Cancer (2022).
    •  

Complete List of Published Work in MyBibliography:

https://pubmed.ncbi.nlm.nih.gov/?term=%28samuels%2C+y%5BAuthor%5D%29+OR+%28samuels-lev%5BAuthor%5D%29&sort=

D. Additional Information: Research Support and/or Scholastic Performance

Ongoing Research Support

2020-2025
Melanoma Research Alliance (#917324)(Smith, Bianchet, Samuels)     $900,000                        Identifying public neoantigens, their TCRs and their rules of engagement

2019-2022             ICRF-COH      220,000$
Identifying PIK3CA neoantigen-specific T cell receptors for cell therapy of solid tumors

2021-2024       Middle East Cooperation grant, German Research Council (DFG)      318,000€          Rationally designed cancer vaccines from a better understanding of the interaction between neoepitope-specific T cells and intratumoral heterogeneity

2020-2025   H20220-FET- OPEN                                                418,000€           

DECOD-Ag

2019-2021
Fundación Ramón Areces (with M.Soengras) 300,000€ Heterogeneity in melanoma metastasis and resistance to immune checkpoint blockade

2018-2023
ERC Consolidator Grant, EU-H2020-ERC-CoG, (770854) Mel-Interactions 2,000,000€

2017-2022
Israel Science Foundation (712811) 300,000₪ Multifaceted analysis of genetically altered signaling hubs in melanoma

Completed Research Support-Selected

2019-2022
Melanoma Research Alliance Established Investigator Award               375,000$
Studying the effects of intra-tumor heterogeneity on anti-tumor immunity                 

2016-2019
Melanoma Research Alliance (712422) (Wargo, Straussman, Admon) Identifying Somatic and Microbial Neo-antigens Associated with Melanoma Responses $900,000

2013-2018
ERC StG grant of the EU (335377) 1,500,000€ MELGEN

2016-2018
Minerva Foundation (712294) Systematic analysis of melanoma driver mutations in genetically engineered mouse models 150,000€

2017-2018
Rising Tide Foundation Combined signatures of neoantigens and T cell receptors as biomarkers for patient stratification in melanoma immunotherapies $100,000

2017-2018
EU-ERC-POC (754282) INTACt 150,000€

2013-2017
Israel Science Foundation (877/13) Systematic Biological and Biochemical Analysis of Somatically Mutated Genes in Melanoma Employing Somatic Cell Knockout and Endogenous Epitope Tagging Technologies 300,000₪

2015-2017
EU-ERC-POC (677645) COMbAT 150,000€