Liran I. Shlush E-Mail: [email protected] Phone: +972 (0)505109815 Citizenship: Israeli DOB: May 21, 1975

Liran I. Shlush E-Mail: Liran.Shlush@Weizmann.Ac.Il Phone: +972 (0)505109815 Citizenship: Israeli DOB: May 21, 1975

Name: Liran I. Shlush E-Mail: [email protected] Phone: +972 (0)505109815 Citizenship: Israeli DOB: May 21, 1975

Senior Scientist Weizmann Institute of Science Department of Immunology Rehovot, Israel

Visiting Physician Ontario Cancer Institute, Princess Margaret Cancer Center, University Health Network. Toronto, Ontario, Canada

Visiting Physician Hematology Department Rambam Healthcare Campus Haifa, Israel

EDUCATION / TRAINING:

INSTITUTION AND LOCATION DEGREE YEAR(s) FIELD OF STUDY

Technion – Israel Institute of Technology PhD 2006-2012 Population Genetics Medical School Technion – Israel Institute of Technology MD 1996-1999 Medicine Medical School Technion – BSc 1993-1996 Medical Science Israel Institute of Technology (cum laude)

A. Positions and Honors (in chronological order)

Positions and Employment Years Position, Place

2015-Current Senior Scientist Weizmann Institute of Science Department of Immunology Rehovot Israel. Visiting physician hematology department Rambam healthcare 2015-Current campus Haifa Israel. Visiting physician hematology Princess Margaret Cancer Center, 2016-Current University Health Network, Toronto Ontario Canada. Clinical fellow leukemia program adult hematology Princess 2014-2015 Margaret Cancer Center, University Health Network, Toronto Ontario Canada. Post-Doctoral Fellow Campbell Family Cancer Research Institute, 2012-2014 Ontario Cancer Institute, Princess Margaret Hospital, University Health Network, Toronto Ontario Canada (Supervisor John E. Dick). Internship - Internal Medicine B Rambam Health Care Campus, 2008-2012 Haifa Israel. PhD Medical Science, Technion – Israel Institute of Technology 2006-2012 (Supervisor Karl Skorecki). 2005 – 2008 Deputy Director, Israel Navy Medical Institute, Haifa, Israel. Medical Commander of Golani Brigade Training Base, Northern 2004-2005 Israel Command, Israel Defense Forces. 2002-2003 Battalion Medical Officer, Israel Defense Forces. Intern – Hematology and Emergency Care, Rambam Hospital, Haifa, 2000-2001 Israel.

Other Experience Years Position, Place Microbial taxonomy and Molecular Biology training, Baylor College, 2000 Houston, Texas. MATLAB Fundamentals and Programming Techniques, Systematics Tel 2008 Aviv. Statistical Analysis for Genetic Epidemiology (SAGE), Sharei Tzedek 2008 Medical Hospital, Jerusalem. Educational Commission for Foreign Medical Graduates (ECFMG) 2010 certified to practice medicine in the U.S.

Honors

2016 Alon Award. Israeli council for higher education.

Keating award. University of Toronto, Divisions of Hematology & 2015 Hematopathology. 2014 Paper of the year award. Canadian Hematology Society. 2014 ASH Scholar award 2015. American Society of Hematology. ASH Abstract Achievement Award. 55th ASH Annual Meeting in New 2013 Orleans, LA. Excellence Award, Teaching, Faculty of Medicine Technion - Israel 2010 Institute of Technology. 2008 The Itai Sharon Rambam Atidim Program and Award. 2003 Excellence Award, First Response Military Medical Care. 2001 Excellence Award, Internship program, Rambam Hospital, Haifa, Israel.

Invited Talks:

1. Shlush LI. Lineage analysis of single cancer cells. Presented as a lecture in the genetic evolution of cancer International Society of Cellular Oncology (ISCO) annual meeting Dresden Germany 2010. 2. Shlush LI. Preleukemia and convergent somatic evolution. Workshop on Mathematical Oncology V: Heterogeneity and Plasticity in Cancer at the Fields Institute, Toronto Canada 2014.

3. Shlush LI. AML an Acute Disease with Chronic evolution. European Hematology Association (EHA) Milan Italy Jun 2014. 4. Shlush LI. The Initiation and Progression of AML. European Hematology Association (EHA) Milan Italy Jun 2014. 5. Shlush LI. Preleukemia Clonal Hematopoiesis and the Aging Bone Marrow. Tsukuba Global Science Week 2014. Tsukuba Japan Sep 2014. 6. Shlush LI. AML relapse mechanisms. Acute leukemia Forum March 2015 San Francisco. 7. Shlush LI. Preleukemia. "Innovations in Hematology". Jerusalem June 2015. 8. Shlush LI. Clonal Evolution Models of Tumor Heterogeneity. 2015 ASCO Annual Meeting Chicago May 2015. As part of the Education Session, which included a chapter in the education book of the ASCO meeting. 9. Shlush LI. Preleukemia the normal side of cancer. International conference on Acute Myeloid Leukemia: “Molecular and Translational: Advances in Biology and Treatment”. Budapest Sep 2015, the European School of Hematology. 10. Shlush LI. On the origins of AML relapse. The 77th Annual Meeting of the Japanese Society of Hematology Oct 2015, Kanazawa Japan. 11. Shlush LI. On the origins of AML 2015. Hematopoietic stem cell regulation symposium WIS Israel. 12. Shlush LI. On the origins of AML relapse. American Society of Hematology annual meeting Orlando FL 2015. 13. Shlush LI. The aging of the human hematopoietic system 2016. CEMMA seminar series Ulm University Germany. 14. Shlush LI. AML clonal evolution. The 29th scientific meeting of the Israeli association for bone marrow transplantation. Ramat-Gan Israel 2016. 15. Shlush LI. The Implications of Leukemia Evolution on Diagnosis and Treatment. Israel Society of hematology and transfusion medicine annual meeting. Nov 2016 Kfar Bloom.

Conference organization/review.

1. ASH annual meeting Orlando 2015. Abstract reviewer and chaired a session on leukemia stem cells.

2. Gaps in the Translation of Basic Research to Effective Treatment in Hematological Malignancies. WIS May 2016. Scientific committee, session chair.

3. ASCO annual meeting Chicago 2016. Abstract reviewer for the educational session.

B. Publications

Peer-reviewed publications [1-17]

1. Shouval R, Shlush LI, Yehudai-Resheff S, Ali S, Pery N, Shapiro E, Tzukerman M, Rowe JM, Zuckerman T: Single cell analysis exposes intra-tumor heterogeneity and suggests that FLT3-ITD is a late event in leukemogenesis. Experimental hematology 2014. 2. Shlush LI, Zandi S, Mitchell A, Chen WC, Brandwein JM, Gupta V, Kennedy JA, Schimmer AD, Schuh AC, Yee KW et al: Identification of pre-leukaemic haematopoietic stem cells in acute leukaemia. Nature 2014. 3. Shlush LI, Selig S: Digital Image Analysis of Cells Stained with the Senescence-Associated beta-Galactosidase Assay. Methods in molecular biology 2013, 1048:11-18. 4. Chapal-Ilani N, Maruvka YE, Spiro A, Reizel Y, Adar R, Shlush LI, Shapiro E: Comparing algorithms that reconstruct cell lineage trees utilizing information on microsatellite mutations. PLoS computational biology 2013, 9(11):e1003297. 5. Shlush LI, Chapal-Ilani N, Adar R, Pery N, Maruvka Y, Spiro A, Shouval R, Rowe JM, Tzukerman M, Bercovich D et al: Cell lineage analysis of acute leukemia relapse uncovers the role of replication-rate heterogeneity and microsatellite instability. Blood 2012, 120(3):603- 612.

6. Shlush LI, Skorecki KL, Itzkovitz S, Yehezkel S, Segev Y, Shachar H, Berkovitz R, Adir Y, Vulto I, Lansdorp PM et al: Telomere elongation followed by telomere length reduction, in leukocytes from divers exposed to intense oxidative stress--implications for tissue and organismal aging. Mechanisms of ageing and development 2011, 132(3):123-130. 7. Shlush LI, Itzkovitz S, Cohen A, Rutenberg A, Berkovitz R, Yehezkel S, Shahar H, Selig S, Skorecki K: Quantitative digital in situ senescence-associated beta-galactosidase assay. BMC cell biology 2011, 12:16. 8. Reizel Y, Chapal-Ilani N, Adar R, Itzkovitz S, Elbaz J, Maruvka YE, Segev E, Shlush LI, Dekel N, Shapiro E: Colon stem cell and crypt dynamics exposed by cell lineage reconstruction. PLoS genetics 2011, 7(7):e1002192. 9. Shlush LI, Bercovici S, Wasser WG, Yudkovsky G, Templeton A, Geiger D, Skorecki K: Admixture mapping of end stage kidney disease genetic susceptibility using estimated mutual information ancestry informative markers. BMC medical genomics 2010, 3:47. 10. Shlush LI, Behar DM, Yudkovsky G, Templeton A, Hadid Y, Basis F, Hammer M, Itzkovitz S, Skorecki K: The Druze: a population genetic refugium of the Near East. PloS one 2008, 3(5):e2105. 11. Shlush LI, Atzmon G, Weisshof R, Behar D, Yudkovsky G, Barzilai N, Skorecki K: Ashkenazi Jewish centenarians do not demonstrate enrichment in mitochondrial haplogroup J. PloS one 2008, 3(10):e3425. 12. Itzkovitz S, Shlush LI, Gluck D, Skorecki K: Population mixture model for nonlinear telomere dynamics. Physical review E, Statistical, nonlinear, and soft matter physics 2008, 78(6 Pt 1):060902. 13. Bercovici S, Geiger D, Shlush L, Skorecki K, Templeton A: Panel construction for mapping in admixed populations via expected mutual information. Genome research 2008, 18(4):661-667. 14. Abramovich A, Shlush L: "Decompression sickness". Aviation, space, and environmental medicine 2008, 79(1):67; author reply 67.

15. Hershkovitz T, Hassoun G, Indelman M, Shlush LI, Bergman R, Pollack S, Sprecher E: A homozygous missense mutation in PEPD encoding peptidase D causes prolidase deficiency associated with hyper-IgE syndrome. Clinical and experimental dermatology 2006, 31(3):435-440. 16. Behar DM, Shlush LI, Maor C, Lorber M, Skorecki K: Absence of HIV- associated nephropathy in Ethiopians. American journal of kidney diseases: the official journal of the National Kidney Foundation 2006, 47(1):88-94. 17. Shlush LI, Behar DM, Zelazny A, Keller N, Lupski JR, Beaudet AL, Bercovich D: Molecular epidemiological analysis of the changing nature of a meningococcal outbreak following a vaccination campaign. Journal of clinical microbiology 2002, 40(10):3565-3571. 18. Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC et al: A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns. Nature 2016, 538(7625):378-382.

Review publications

1. Shlush, LI, Minden MD. Preleukemia: The Normal Side of Cancer. Current Opinion in Hematology, 2015. 2. Shlush LI, Hershkovitz D: Clonal evolution models of tumor heterogeneity. American Society of Clinical Oncology educational book ASCO American Society of Clinical Oncology Meeting 2015, 35:e662- 665. 3. Shlush LI, Mitchell, A.: AML evolution from preleukemia to leukemia and relapse. Best Practice & Research Clinical Haematology 2015. 28 (2-3): 81-9. 4. Shlush LI, Zandi S, Itzkovitz S, Schuh AC: Aging, clonal hematopoiesis and preleukemia: not just bad luck? International journal of hematology 2015. 102 (5): 513-22. 5. Shlush LI: Change comes like a little wind: tales in MDS evolution. Blood 2016, 128(9):1162-1163.

Abstracts

1. Shlush LI, Behar MD, Lorber M, Carcom M, Skorecki K. Ethiopians Do Not Share Susceptibility to HIV Associated Nephropathy with African Americans. Presented at the 2004 American Society of Nephrology annual meeting, Saint Louis, Missouri, Poster. 2. Shouval R, Shlush LI, Ali S, Shapiro E, Rowe JM, Zuckerman T. FLT-3 mutations in single leukemia cells more than meets the eye. Presented at the International Society of Hematology Jerusalem 2010, poster. 3. Liran I Shlush, Noa Chapal, Rivka Adar, Shai Izraeli, Jacob M. Rowe, Karl Skorecki, Ehud Shapiro and Tsila Zuckerman. Single-Cell Phylogenetic analysis provides Novel Insight into Resistance Mechanisms in AML. 52th ASH Annual Meeting Orlando 2010, Oral presentation. 4. Liran I Shlush, Amanda Mitchell, John E. Dick. The contribution of sub- clonal genetic diversity of human acute myeloid leukemia to therapy failure. Cold Spring Harbor Laboratory Cancer Biology & Therapeutics meeting 2013, Oral presentation. 5. Liran I. Shlush, Sasan Zandi, Amanda Mitchell, Weihsu Claire Chen, Joseph M. Brandwein, Vikas Gupta, James A. Kennedy, Aaron D. Schimmer, Andre C. Schuh, Karen W. Yee, Jessica McLeod, Monica Doedens, Jessie Medeiros, Rene Marke, Hyeoung Joon Kim, Kwon Lee, John D. McPherson, Thomas J. Hudson, The HALT Pan-Leukemia Gene Panel Consortium, Andrew M.K. Brown, Quang M. Trinh, Lincoln D. Stein, Mark D. Minden, Jean C.Y. Wang, John E. Dick. DNMT3a Mutations Define a Pre-Leukemic Stem Cell Reservoir In Human Acute Myeloid Leukemia. 55th ASH Annual Meeting New Orleans, 2013, Oral presentation.

C. Academic Activity:

Title Dates Institute Name Research area MSC 2016- The Maxim The functional phenotypic Students Current Weizmann Kushnir consequences of preleukemic Institute of mutations. Science 2016- The Dr. Roni Mechanisms of preleukemic mutation Current Weizmann (Aharon) selective advantage and progression Institute of Gefen to leukemia PhD Science Students 2016- The Dr. Amos The Relative Contribution of Different PhD Current Weizmann Tuval (MD) Pre-Leukemic & Leukemic Mutation to Students Institute of Tumor Fitness Science

2015- The Wigelman The clonal structure of the

Current Weizmann Yoav hematopoietic system in health and

Institute of disease Post Science Doctoral 2016- The De-Morgan The mutation accumulation training Current Weizmann Aviv mechanisms in the evolution of Institute of leukemia Science 2015- The Yoni Lab Current Weizmann Moskovitz Technician Institute of Science 2016- The Dr. Nathali Assistant Current Weizmann Kaushansky Staff Institute of Scientist Science

D. Grants:

1. The Deborah grant from the Technion security program 2006. Telomere Biology and DNA Damage in Divers and Cells Exposed to High Levels of oxygen. PI Karl Skorecki; Budget 21,000$. 2. The Itai Sharon Rambam Atidim Program and Grant 2008. PI Karl Skorecki; Budget 38,000$. 3. Israel cancer association 2010-2012. Phylogentic analysis of single leukemia cells, in the study of relapse mechanisms. PI Tsila Zuckerman; Budget 30,000$. 4. McEwen Centre for Regenerative Medicine Postdoctoral Fellowship grant 2011-2016. Identification of genetically diverse subpopulations and their evolutionary relationship within human AML and leukemic stem cells using clonal analysis of diagnosis, relapse and Xenograft samples. PI John Dick; Budget 220,000 CAD. 5. Leukemia & Lymphoma Society Quest for CURES (QFC) 2014. Assessing risk of leukemic progression in individuals carrying preleukemic mutations as a guide to early diagnosis and treatment in acute myeloid leukemia (AML). PI Mark Minden CO-investigator Liran Shlush, Jean Wang. Budget 800,000 USD. 6. Princess Margaret Cancer Center startup grant 2014-2016.The preleukemia program PI Liran Shlush. Budget 386,000 CAD. 7. Sponsored Research Agreement with Imago Biosciences 2015. The preleukemia program in AML, PI Liran Shlush. Budget 40,000 CAD. 8. The Itai Sharon Rambam Atidim Program and Grant 2016. PI Liran Shlush; Budget 60,000 USD. 9. Weizmann institute of science startup grant 2015-2018. Budget 1,250,000 USD. 10. Abisch Frenkel Grant 2016. Budget 45,000 USD. 11. ERC-2016-STG grant. Understanding the mechanisms of human acute myeloid leukaemia (AML) evolution (Proposal 714731 - MAMLE). 1,750,000 Euro. Start Jan 2017 for 5 years.

E. Intellectual property January 2014 “Identification of Pre-leukemic hematopoietic stem cell in human acute myeloid leukemia”, Patent numbers: US61/929,420; US61/938,551; CA2,842,635; Inventors: John E Dick, Mark Minden, Sasan Zandi, Jean Wang, Liran Shlush.