Eytan Ruppin, M.D., Ph.D.

Eytan Ruppin, M.D., Ph.D.

Eytan Ruppin, M.D., Ph.D., is a computational biologist whose research is focused on developing and harnessing data science approaches for the integration of multi-omics data to better understand the pathogenesis of cancer, its evolution and treatment. We collaborate with many experimental cancer labs, aiming to develop and utilize computational approaches to jointly gain a network-level integrative view of the systems we study. From a translational perspective, together with our collaborators, we aim to predict and test novel drug targets and biomarkers to treat cancer more effectively.

Areas of Expertise

1) big data analysis, 2) machine learning, 3) bioinformatics and computational biology, 4) genome-scale metabolic modeling, 5) genetic interactions in cancer, 6) precision medicine, 7) immunotherapy

Contact Info

Eytan Ruppin, M.D., Ph.D.
Center for Cancer Research
National Cancer Institute
Building 15C1
Bethesda, MD 20892
Ph: 240-858-3169

1. The discovery of genetic interactions in cancer as a basis for advancing genome-wide based cancer treatments

A main focus in cancer research is on studying a few hundred cancer driver genes, to identify ‘actionable’ mutations that can be targeted therapeutically. Complementing this approach, my lab has focused in recent years on studying the value of genetic interactions (GIs) between genes across the whole genome to advance cancer research and treatment. This approach has been motivated by recent work in our lab and others showing that (i) genetic interactions between genes are critical in tumor development and drug response, and that (ii) such interactions can be computationally identified by analyzing large-scale genomics and patient data. This work encompasses several types of genetic interactions (GI) that are relevant to cancer therapeutics, including Synthetic Lethal (SL) interactions, Synthetic Dosage Lethal (SDL) interactions and Synthetic Rescue (SR) interactions. Based on the tools we have developed for the data-driven identification of all three types of GI networks from large cohorts of tumor samples, we have shown that the cancer GIs identified can be successfully used for a variety of important challenges including: (a) Generating the first clinically-derived pan-cancer SL and SDL networks, we show that these networks can successfully predict the response of cancer patients to many widely used drug treatments, offering a complementary approach to existing mutation-based methods for precision-based cancer therapy. (b) Aiming to fight resistance to cancer therapy, we have identified genome-wide pancancer SR networks, which are predictive of patients’ drug response and resistance to the majority of current cancer drugs. This approach provides a basis for new combination-based therapeutic strategies improving the effectiveness of existing cancer therapies by identifying and targeting drug resistance pathways.

Going forward in this line of research, we intend to explore two main paths: (a) precision medicine – inferring patient specific GI-mediated drug response by analyzing the transcriptomics of their tumors, and (b) drug development – identifying new SL-based drug targets, combined with their SL-derived patient stratification profiles.  

2. Cancer immunotherapy

In the last two years we have become actively engaged in collaborative studies in cancer immunotherapy, ranging from studying the role of urea cycle dysregulation in modulating the response to checkpoint inhibitors in different cancer types, studying the role of intratumor heterogeneity in shaping the immune response and its effectiveness, and very recently, building machine learning based predictors of patients’ response to checkpoint therapies in melanoma. Ongoing collaborative studies focus on genome wide identification of effective combinations involving checkpoint inhibitors (possibly with targeted therapies) and on the identification of new targets for CAR-T therapy.

NIH Scientific Focus Areas:
Cancer Biology, Computational Biology, Genetics and Genomics, Immunology, Systems Biology
  1. Mahashweta Basu, Kun Wang, Eytan Ruppin**, Sridhar Hannenhalli**(**corresponding authors)
    Science Advances. 7/14: 2021. Full-Text Article [ Journal Article ]
  2. Kuoyuan Cheng, Nishanth Ulhas Nair, Joo Sang Lee, Eytan Ruppin
    Science Advances. 7/1: 2021. Full-Text Article [ Journal Article ]
  3. Kalaora S, Lee JS, Barnea E, Levy R, Greenberg P, Alon M, Yagel G, Bar Eli G, Oren R, Peri A, Patkar S, Bitton L, Rosenberg SA, Lotem M, Levin Y, Admon A, Ruppn E**, Samuels Y**(** corresponding authors)
    Nature Communications. 896: Nature Publishing Group 2020. [ Journal Article ]
  4. Noam Auslander, Daniel M. Ramos, Ivette Zelaya, Hiren Karathia, Thomas O. Crawford, Alejandro A. Schaffer, Charlotte J. Sumner, Eytan Ruppin
    Molecular Systems Biology. Vol 16/Issue 12: EMBO Press 2020. Full-Text Article [ Journal Article ]
  5. Targeting purine synthesis in ASS1-expressing tumors enhances the response to immune checkpoint inhibitors.
    Rom Keshet, Joo Sang Lee, Lital Adler, Muhammed Iraqi, Yarden Ariav, Lisha Qiu Jin Lim, Shaul Lerner, Shiran Rabinovich, Roni Oren, Rotem Katzir, Hila Weiss Tishler, Noa Stettner, Omer Goldman, Hadas Landesman, Sivan Galai, Yael Kuperman, Yuri Kuznetsov, Alexander Brandis, Tevi Mehlman, Sergey Malitsky, Maxim Itkin, S. Eleonore Koehler, Yongmei Zhao, Keyur Talsania, Tsai-wei Shen, Nir Peled, Igor Ulitsky, Angel Porgador, Eytan Ruppin**, Ayelet Erez** (**corresponding authors)
    Nature Cancer. Vol 1: 894-908, 2020. Full-Text Article [ Journal Article ]

Eytan Ruppin received his M.D. and Ph.D. (Computer Science) from Tel-Aviv University where he has served as a professor of Computer Science & Medicine since 1995, conducting computational multi-disciplinary research spanning a wide variety of topics, including neuroscience, evolutionary computation, natural language processing, machine learning and systems biology. He joined the University of Maryland in July 2014 as a Computer Science professor and director of its center for bioinformatics and computational biology (CBCB), before joining the NCI in January 2018. He received the Rothschild and Alon fellowships, the Schtacher Award and a McDonnell Foundation grant award and is a member of the editorial board of EMBO Reports and Molecular Systems Biology. He is a co-founder of startup companies involved in precision medicine and cancer drug discovery.

Name Position
Camilo Calvo-Alcaniz Postbaccalaureate Fellow (CRTA)
Kouyuan Cheng BSc. Predoctoral Visiting Fellow (Graduate Student)
David R. Crawford Ph.D. Postdoctoral Fellow (CRTA)
Katie Farney BSc. Predoctoral Fellow (Graduate Student)
Alfred Xavier Garcia BSc. Postbaccalaureate Fellow (CRTA)
E. Michael Gertz, Ph.D. Staff Scientist
Leandro Hermida BSc. Predoctoral Visiting Fellow (Graduate Student)
Sanna Madan BSc. Predoctoral Fellow (CRTA)
Nishanth Ulhas Nair, Ph.D. Staff Scientist
Sushant Patkar BSc. Predoctoral Visiting Fellow (Graduate Student)
Lipika Ray, Ph.D. Staff Scientist
Wells Robinson BSc. Predoctoral Visiting Fellow (Graduate Student)
Alejandro A. Schäffer, Ph.D. Staff Scientist
Fiorella Schischlik Ph.D. Postdoctoral Fellow (Visiting)
Neelam Sinha MSc. Postbaccalaureate Fellow (Visiting)
Sanju Sinha BSc. Predoctoral Visiting Fellow (Graduate Student)
Rahulsimham Vegesna Ph.D. Postdoctoral Fellow (CRTA)
Binbin Wang Ph.D. Postdoctoral Fellow (Visiting)
Kun Wang Ph.D. Postdoctoral Fellow (Visiting)
Philippe Youkharibache, Ph.D. Staff Scientist