CURRICULUM VITAE Mazhar ADLI, Ph.D. Assistant professor University of Virginia, School of Medicine Department of Biochemistry and Molecular Genetics www.adlilab.org Cell: 919-360-8327 Office: 434-243-8567 Email: [email protected] Address: 1340 Jefferson Park Ave Charlottesville, VA, 22908 EDUCATION Postdoctoral Training, Epigenomics…………………………..……………………………………………2007-2012 Broad Institute and Massachusetts General Hospital, Harvard Medical School Advisor: Prof. Bradley E. Bernstein Ph.D., Molecular Biology………………………………………………………………………………..……2002-2007 The University of North Carolina at Chapel Hill, NC, USA Advisor: Prof. Albert S. Baldwin M.Sc., Biological Sciences and Bioengineering….……………………………………………..…………….2000-2002 Sabanci University, Istanbul, Turkey Advisor: Prof. Huveyda Basaga B.S., Molecular Biology…………………………………………………...………………………..…………1995-2000 Middle East Technical University, Ankara, Turkey B.A., Science Education……………………………………………………...………………………..………1995-2000 Middle East Technical University, Ankara, Turkey PROFESSIONAL POSITIONS Assistant Professor (tenure-track)…………………..……………...…………………………………09/2012-Present University of Virginia, School of Medicine, Department of Biochemistry and Molecular Genetics Active Member, American Association of Cancer Research (AACR)…………….....................................2016-Present Member, faculty search committee, UVA department of Biochemistry..……………….................................2014-2015 Member, Grant review committee, Welcome Trust, UK………...…………………………..…………..……2015 Member, NASA International Life Sciences Research grant review panel ……..…...………………………2014 Member, NIH/ NIEHS review panel, TaRGET I (R01)...…………………...………………….………… March, 2013 Founding Member, Boston Biologist Colloquium of Harvard Medical School.……..…....……...…...… 2011-Present Postdoctoral Research Fellow……………………..………………...………………………….…….09/2007-08/2012 Harvard Medical School, Massachusetts General Hospital, Broad Institute Research Assistant.……………….……………………………..……...………………………………….....2002-2007 The University of North Carolina at Chapel Hill, Department of Biology, NC, USA Research Assistant.……………….……………………………….…………........……………………….....2000-2002 Sabanci University, Istanbul, Turkey HONORS & AWARDS V Scholar plus award, V foundation for cancer research.…….……….….................................................2016-present V Scholar, V foundation for cancer research.…….……….…......................................……………...............2014-2016 STARR Cancer Consortium Visiting Fellow Award….…..…….……….…...……………...............…………...2011 Sabanci Scholarship (Tuition and Stipend)….…………….……………...…………………..............……...2000-2002 Sabanci University, Istanbul, Turkey President’s High Honor Graduate Award (Ranked 1st in the Graduate School)…...……………………….........2002 Graduate School of Biological Sciences and Bioengineering, Sabanci University, Istanbul, Turkey Presidential-METU Scholarship (tuition and stipend) …...…………………………...…………………….1995-2000 Middle East Technical University, Ankara, Turkey 1 President’s Honor Student Award (both in Major and Double Major Programs)………..…...……………1995-2000 Middle East Technical University, Ankara, Turkey PUBLICATIONS Published Articles: 1. Kuscu, Parlak M, Tufan T, Yanh J, Szlachta K, Mammeadov R, Adli M. CRISPR-STOP: Gene silencing through base editer-induced nonsense mutations Nature Methods, 2017 (January 2017, accepted in principle) 2. Peiwu Q*, Parlak M*, Kuscu C, Bandaria J, Singh R, Yildiz A & Adli M. Multicolor labeling and imaging nuclear organization of native chromatin loci with type II CRISPR/Cas9 system in living cells. Nature Communication, 2017 * Equally Contributed 3. Kuscu C & Adli M. CRISPR/Cas9-AID base editor is a powerful gain of function screening tool. Nature Methods, 2016. DOI: 10.1038/nmeth.4076. 4. Ataman B, Boulting GL, Harmin DA, Yang MG, Baker-Salisbury M, Yap EL, Malik AN, Mei K, Rubin AA, Spiegel I, Durresi E, Sharma N, Hu LS, Pletikos M, Griffith EC, Partlow JN, Stevens CR, Adli M, Chahrour M, Sestan N, Walsh CA, Berezovskii VK, Livingstone MS, Greenberg ME. 1. Evolution of Osteocrin as an activity-regulated factor in the primate brain. Nature, 2016. DOI: 10.1038/nature20111. 5. Illendula N, Gilmour J, Grembecka J, Tirumala V.S.S, Boulton A, Kuntimaddi A, Schmidt C, Wang L, Pulikkan JA, Zong H, Parlak P, Kuscu C, Pickin A, Zhou Y, Gao Y, Mishra L, Adli M, Castilla LH, Rajewski RA, Janes KA, Guzman ML, Bonifer C, Bushweller JH. Small Molecule Inhibitor of CBFβ-RUNX Binding for RUNX Transcription Factor Driven Cancers. EBioMedicine, 2016. DOI: http://dx.doi.org/10.1016/j.ebiom.2016.04.032 6. Anderson CJ, Clark DE, Adli M, Kendall MM. Ethanolamine Signaling Promotes Salmonella Niche Recognition and Adaptation during Infection. PLoS Pathogen, 2015. DOI: 10.1371/journal.ppat.1005278. 7. Singh R, Kuscu C, Quinlan A, Qi Y & Adli M, Cas9-Chromatin binding information enables more accurate CRISPR Off-target Prediction. Nucleic Acid Research, 2015. DOI: 10.1093/nar/gkv575. 8. Kuntimaddi A, Achille NJ, Thorpe J, Lokken AA, Singh R, Hemenway CS, Adli M, Zeleznik-Le NJ, Bushweller JH. Degree of Recruitment of DOT1L to MLL-AF9 Defines Level of H3K79 Di- and Trimethylation on Target Genes and Transformation Potential. Cell Reports, 2015. DOI: 10.1016/j.celrep.2015.04.004. 9. Roadmap Epigenomics Consortium. Integrative analysis of 111 reference human epigenomes. Nature, 2015. DOI: 10.1038/nature14248. 10. Qin F, Song Z, Babiceanu M, Song Y, Facemire L, Singh R, Adli M& Li H. Discovery of CTCF-sensitive cis-spliced fusion RNAs between adjacent genes in human prostate cells. PloS Genetics, 2015. DOI: 10.1371/journal.pgen.1005001. 11. Adli M, Parlak M, Li Y, El-Dahr S. Epigenetic States of Nephron Progenitors and Epithelial Differentiation. J Cell Biochem, 2015. DOI: 10.1002/jcb.25048. 12. Rubeis et al.(Adli M: consortium collaborator). Synaptic, transcriptional and chromatin genes disrupted in autism. Nature, 2014. DOI: 10.1038/nature13772. 2 13. Kuscu C, Arslan S, Singh R, Thorpe J, Adli M. Genome-wide analysis reveals characteristics of off-target sites bound by the Cas9 endonuclease. Nature Biotechnology, 2014. DOI: 10.1038/nbt.2916. 14. Rissman EF, Adli M. Transgenerational epigenetic inheritance: focus on endocrine disrupting compounds. Endocrinology, 2014. DOI: 10.1210/en.2014-1123. 15. Abdel-Wahab O*, Gao j*, Adli M*, Dey A, Trimarchi T, Rock Chung RY, Kuscu C, Hricik T, Lobry ND, La Fave L, Koche R, Shih AH, Guryanova OA, Pandey S, Shin Y, Bhatt PK, Monette S, Taylor JE, Zhao X, Jaffe JD, Dixit V, Park CY, Bernstein BE, Aifantis I, and Levine RL. Deletion of Asxl1 Results in Myelodysplasia and Severe Developmental Defects in Vivo. Journal of Experimental Medicine, 2013. DOI: 10.1084/jem.20131141, PMCID: PMC3832937. *Equally contributed 16. Zhu J* & Adli M*#, Zou J, Verstappen G, Coyne M, Zhang X, Durham T, Miri M, Deshpande V, De Jager PL, Bennett DA, Houmard JA, Muoio DM, Onder TT, Camahort R, Cowan C, Meissner A, Epstein CB, Shoresh N and Bernstein BE#. Genome-wide chromatin state transitions associated with developmental and environmental cues. Cell, 2013. DOI: 10.1016/j.cell.2012.12.033 PMCID: PMC3563935. *Equally contributed, #Co-corresponding author. 17. T.W. Yu, M.H. Chahrour, M.E. Coulter, S. Jiralerspong, K. Okamura-Ikeda, B. Ataman, D.A. Harmin, Adli M, A.N. Malik, A. D'Gama, K. Schmitz-Abe, E. Lim, S.J. Sanders, G.H. Mochida, J.N. Partlow, C.M. Sunu, J.M. Felie, J. Rodriguez, J. Ware, R.M. Joseph, R.S. Hill, B.Y. Kwan, M. Al-Saffar, N.M. Mukaddes, A. Hashmi, S. Balkhy, G.G. Gascon, F.M. Hisama, E. LeClair, A. Poduri, O. Oner, S. Al-Saad, T. Ben-Omran, L. Al-Gazali, V. Eapen, C.R. Stevens, L. Rappaport, S.B. Gabriel, K. Markianos, M.W. State, M.E. Greenberg, H. Taniguchi, N.E. Braverman, E.M. Morrow, C.A. Walsh. Using whole exome sequencing to identify inherited causes of autism. Neuron, 2013. DOI: 10.1016/j.neuron.2012, PMCID: PMC3694430. 18. AbdelWahab O*, Adli M*, LaFave LM, Gao J, Hricik T, Shih AH, Pandey S, Patel JP, Chung YR, Koche R, Perna F, Zhao X, Taylor JE, Park CY, Carroll M, Melnick A, Nimer SD, Jaffe JD, Aifantis I, Bernstein BE, Levine RL. ASXL1 mutations promote myeloid transformation through loss of PRC2-mediated gene repression. Cancer Cell. 2012. DOI: 10.1016/j.ccr.2012.06.032, PMCID: PMC3422511. *Equally contributed 19. Adli M, Bernstein BE. Whole-genome chromatin profiling from limited numbers of cells using nano-ChIPseq. Nature Protocols, 2011. DOI: 10.1038/nprot.2011.402. NIHMSID: NIHMS427239. 20. Adli M, Zhu J, Bernstein BE. Genome-wide chromatin maps derived from limited numbers of hematopoietic progenitors. Nature Methods. 2010. DOI: 10.1038/nmeth.1478, PMCID: PMC2924612. 21. Goren A, Ozsolak F, Shoresh N, Ku M, Adli M, Hart C, Gymrek M, Zuk O, Regev A, Milos PM, Bernstein BE. Chromatin profiling by directly sequencing small quantities of immunoprecipitated DNA. Nature Methods, 2010. DOI: 10.1038/nmeth.1404, PMCID: PMC2862482. 22. Ku M, Koche RP, Rheinbay E, Mendenhall EM, Endoh M, Mikkelsen TS, Presser A, Nusbaum C, Xie X, Chi AS, Adli M, Kasif S, Ptaszek LM, Cowan CA, Lander ES, Koseki H, Bernstein BE. Genome-wide analysis of PRC1 and PRC2 occupancy identifies two classes of bivalent domains. PLoS Genetics, 2008. DOI: 10.1371/journal.pgen.1000242, PMCID: PMC2567431. 23. Koppikar P, Bhagwat N, Kilpivaara O, Manshouri T, Adli M, Hricik T, Liu F, Saunders LM, Mullally A, Abdel-Wahab O, Leung L, Weinstein A, Marubayashi S, Goel A, Gönen M, Estrov Z, Ebert BL, Chiosis G, Nimer SD, Bernstein BE, Verstovsek S, Levine RL. Heterodimeric JAK-STAT activation as a mechanism of persistence to JAK2 inhibitor therapy. 3 Nature, 2012. DOI: 10.1038/nature11303, PMCID: PMC3991463. 24. Chapman MA, Lawrence MS, Keats JJ, Cibulskis K, Sougnez C, Schinzel AC, Harview CL, Brunet JP, Ahmann GJ, Adli M, Anderson KC, Ardlie KG, Auclair D, Baker A, Bergsagel PL, Bernstein BE, Drier Y, Fonseca R, Gabriel SB, Hofmeister CC, Jagannath S, Jakubowiak AJ, Krishnan A, Levy J, Liefeld T, Lonial S, Mahan S, Mfuko B, Monti S, Perkins LM, Onofrio R, Pugh TJ, Rajkumar SV, Ramos AH, Siegel DS, Sivachenko A, Stewart AK, Trudel S, Vij R, Voet D, Winckler W, Zimmerman T, Carpten J, Trent J, Hahn WC, Garraway LA, Meyerson M, Lander ES, Getz G, Golub TR. Initial genome sequencing and analysis of multiple myeloma. Nature, 2011. DOI: 10.1038/nature09837, PMCID: PMC3560292. 25. Koche RP, Smith ZD, Adli M, Gu H, Ku M, Gnirke A, Bernstein BE, Meissner A. Reprogramming factor expression initiates widespread targeted chromatin remodeling. Cell Stem Cell. 2011. DOI: 10.1016/j.stem.2010.12.001, PMCID: PMC3220622. 26. Adli M, Merkhofer E, Cogswell P, Baldwin AS. IKKalpha and IKKbeta each function to regulate NF-kappaB activation in the TNF-induced/canonical pathway. PLoS One, 2010. DOI:10.1371/journal.pone.0009428. PMCID: PMC2828475. 27. Dan HC, Adli M, Baldwin AS. Regulation of mammalian target of rapamycin activity in PTEN-inactive prostate cancer cells by I kappa B kinase alpha. Cancer Research, 2007. PMID: 17616684. 28. Adli M, Baldwin AS. IKK-i/IKKepsilon controls constitutive, cancer cell-associated NF-kappaB activity via regulation of Ser-536 p65/RelA phosphorylation. Journal of Biological Chemistry. 2006 Sep 15;281(37):26976-84. PMID: 16840782. 29. Kutuk O, Adli M, Poli G, Basaga H. (2004). Resveratrol protects against 4-HNE induced oxidative stress and apoptosis in Swiss 3T3 fibroblasts. Biofactors. 2004; 20(1):1-10. PMID: 15096656. PATENTS 1. Adli M. Using in vivo CRISPR screening viability scores to predict therapeutic response of cancer drugs (Application submitted, September 2016) 2. Adli M, Mikkelsen T, Bernstein BE. Methods for preparing high throughput sequencing libraries from scarce amount of DNA. Patent #: USA, 12/699,508 RESEARCH SUPPORT GF13102 Adli (PI) 01/10/14 – 09/30/16 The V Foundation for Cancer Research Epigenetic Engineering to Correct an Aberrantly Regulated Locus in Cancer The goal of this study is to use novel epigenetic engineering tools to change and reprogram aberrant chromatin state and function at specifically targeted genomic regions. Role: PI 5 R01ES022759-02 Rissman (PI) 06/15/14 – 02/28/19 NIH/NIEHS Transgenerational actions of the endocrine disrupting compound Bisphenol A The aim is to determine the parent of origin and mechanisms by which Bisphenol A has transgenerational actions on gene expression and behavior. Role: Co-Investigator 4 Completed Research Support 5 P50 DK096373-03 Gomez (PI) 09/01/14 – 08/31/15 NIH/NIDDK Kidney development cell fate and precursors of disease in the young and adult Pilot Project: CRISPR mediated whole-genome knock-out screening to identify essential genes in nephrovascular development The aim of this Pilot Project is to target every single gene in the genome by more than 10 unique sgRNAs to achieve CRISPR/Cas9 mediated genetic knock-outs. This will allow identification of essential genes for a specific cellular phenotype; the genes that are positively or negatively regulating a given phenotype or a cellular state. Role: PI (Pilot Project) CaTS Pilot Project Adli (PI) 11/01/14 – 10/31/15 UVA Cancer Center & NCI CCSG P30 CA44579 In vivo CRISPR based knock-out screening to identify essential epigenetic regulators of tumor progression in xenograft model of pancreatic cancer The aim of this project is to use CRISPR gene editing technology to perform knock screenings to identify essential genes involved in in vivo tumor progression and chemotherapy resitance in PDAC. Role: PI CaTS Pilot Project Zhong & Adli (co-PI) 11/01/14 – 10/31/15 UVA Cancer Center & NCI CCSG P30 CA44579 Targeting Radiation Resistance in Glioma The aim of this project is to identify the mechanism of radioresistance glioblastoma. The Adli lab will perform an unbiased genome-wide CRISPR gene knock-out screening to identify essential genes responsible for radioresistance. Role: Co-PI ACS-IGR Adli (PI) 11/2012 – 11/2013 American Cancer Society Institutional Research Grant Characterizing genomic targets and epigenetic aberrations due to ASXL1 and EZH2 mutations in myeloid malignancies Role: PI Pending Research Support: 1R01 CA211648-01 (2 percentile score) Adli (PI) 01/17–12/20 NIH/NCI $323,201 Title: Identifying the Drivers and Targeting Chemo Resistance in Ovarian Cancer The overall goal of our research has focused on understanding the genetic and epigenetic basis of chemoresistance in ovarian cancer. Our in preliminary results suggest that aberrant regulation at specific sets of distal regulatory sites in the genome called super enhancers drive the chemo resistance in ovarian cancer. We hypothesize that the development of chemoresistance in ovarian cancer is mediated, at least partially, by epigenetic alterations at these regulatory genomic elements. The overarching goal of this proposal is to characterize the functional roles of these elements in vivo and characterize the role of genes that are targets of these elements. 1R01CA215713-01 (22 percentile, 1st submission, resubmitted) 5 Adli (PI) 04/17-03/22 NIH/NCI $312,701 Title: Identifying novel drug targets in pancreatic cancer through in vivo screening We are presenting evidence that genome-scale genetic knockout (KO) screenings in in vivo propagated, patientderived tumors can be used to identify novel drug targets for pancreatic cancer. We have already demonstrated the power of this approach in our preliminary results. In this proposal, we will validate our preliminary findings and perform additional screenings to identify novel drug targets, which can be utilized to enhance the therapeutic response of standard of care chemotherapy agents for pancreatic cancer. INVITED TALKS (National and International) 1. Temporal and spatial epigenome editing allows precise gene regulation 41st Federation of European Biochemical Societies (FEBS), 2016, Izmir, TURKEY 2. Manipulating Chromatin structure and function Molecular Biology Association of Turkey, 2016, Denizli, TURKEY 3. Dual labeling and imaging chromatin structure using CRISPR technology Biological and clinical frontiers in epigenetic, Epicypher 2016, San Juan, PUERTO RICO 4. Understanding and manipulating human epigenome Turkish biochemical society annual meeting, 2015, Antalya, TURKEY 5. How to perform and publish high impact science. Turkish biochemical society annual meeting, 2015, Antalya, TURKEY 6. Using CRISPR to do locus specific epigenome editing and chromatin visualization Gordon Research Conference, Cell Growth & Proliferation, 2015, Mount Snow, VT, USA 7. Understanding the CRISPR targeting specificity Functional Genomics & Predictive Medicine, Boston, MA, USA, May 2015 8. Understanding and manipulating human epigenome Memorial Sloan Kettering Cancer Center, HOPP, New York, NY, USA March 2015 9. Understanding and manipulating human epigenome East Carolina University, Grenville, NC, USA April 2015 10. Understanding and manipulating human epigenome Koc University, Istanbul, Turkey, Nov 2014 11. Understanding and manipulating human epigenome Sabanci University, Istanbul, Turkey, Nov 2014 12. Understanding and manipulating human epigenome Bogazici University, Istanbul, Turkey, Nov 2014 13. Whole genome analysis of CRISPR/Ca9 targeting specificity FASEB Genome Engineering meeting, Nassau, Bahamas, June 2014 6 14. Manipulating the human epigenome with CRISPR technology National Institute of Health, NCI, Bethesda, MD, USA, May 2014 15. Understanding Human Epigenome University of Virginia, Center for Public Health Genomic, Charlottesville, VA, USA, November 2013 16. Comparative analysis of human epigenomic maps Epigenomics: A Roadmap to the Living Genome Meeting (NIH), Boston, USA October 2013 17. Chromatin state transition in response to developmental and environmental cues. World Epigenetics Summit, Boston, USA, July 2013 18. Human epigenome in normal and malignant settings 13th International Stroke Genetics Consortium, Charlottesville, VA, April, 2013 19. Large scale chromatin and cellular state transitions University of Virginia, School of Medicine, January 2013 20. Understanding human epigenome University of Chicago, Chicago, IL, March 2012 21. Whole genome mapping of human epigenome University of California at Riverside. Riverside, CA, February 2012 22. Human epigenome reveals dynamics of cellular state transitions Arizona state university, Phoenix, AZ, January, 2012 23. Understanding the whole genome mapping of human epigenome University of Wisconsin at Madison, Madison, WI, December 2011 24. Epigenomic landscape of primary and ex vivo expanded hematopoietic stem cells Fred Hutchinson Cancer Research Center, Seattle, WA, USA, September 2010 25. Epigenomic landscape in hematopoietic development Koc University, Istanbul, Turkey, January 2010 26. Large-scale epigenomic studies in hematopoietic development and disease Sabanci University, Istanbul, Turkey, January 2010 27. Genome-wide maps of protein-DNA interactions by high throughput DNA sequencing Health, Science and Technology Workshop, Bosphorus University, Istanbul, Turkey, December 2009 28. Large-Scale Studies of the Epigenetics of Human Leukemia STARR Cancer consortium, Cold Spring Harbor Laboratories, Cold Spring Harbor, NY, USA, September 2009 29. Epigenomic landscape in hematopoietic development and disease Cancer Genomics Platform, Broad Institute, Cambridge, MA, USA, November 2009 30. Genome-wide chromatin state analysis of pluripotent and multi-potent stem cells MGH Cancer Center, MGH Navy Yard, Boston, MA, USA, October 2009 TEACHING EXPERIENCE Chromatin II (BIOC814): Cancer Epigenetics…….……………………………....………….……....….………2016 7 Chromatin II (BIOC814): Epigenome Editing…….………………………………………….…….....…………2016 PHS5500: Genome editing technologies…….………………………………...……………….…….....…………2016 BIMS Core Course, Genome editing technologies…….………………………………...…….……....…………2015 SoM, Foundations of Molecular Medicine, Molecular Medicine Techniques…….………………..………..…2015 BIMS Core Course, Nucleosome remodeling…….…………………...…………………………..………...……2015 SoM, Foundations of Molecular Medicine, Molecular Medicine Techniques…….………….….…………..…2015 BIMS Core Course, Genome editing technologies…….…………………...…………………..………...………2014 Teaching assistant (Introduction to Genetics).…………….………………….……...………………...…….2003-2004 The University of North Carolina at Chapel Hill, Department of Biology Teaching assistant (Natural Sciences 101: Introduction to Biology).……………..……………………...….2001-2002 Sabanci University, Biological Sciences and Bioengineering Program, Istanbul, Turkey Substitute high school biology teacher…….……………………………………………………..……...….1999-2000 Private Ari High School, Ankara, Turkey MENTORING EXPERIENCE: Postdoctoral fellows: 1. Cem Kuscu 2. Jiekun Yang 3. Tom Xiaolong 4. Karol Szlachta 5. Sevki Arslan 6. Mahmut Parlak 7. Rashad MemMedow PhD committees: 1. Stephen Sang (PI: Mazhar Adli) 2. Ritambhara Singh (co-PI: Mazhar Adli) 3. Steve Griffith (PI: Gary Owens) 4. Charles Goforth (PI: Gary Owens) 5. Magdalena Cichewicz (PI: Anindya Dutta) 6. Bruno Takao (PI: Anindya Dutta) 7. Brian Reon (PI: Anindya Dutta) 8. Peter Balogh (PI: Adem Goldfarb) 9. Luke Oosdyk (Bryce Paschal) 10. Erin Harris (PI: Emilie Rissman) 11. Gabriel Falco Alencar (PI: Gary Owens) 12. Aravinda Kuntimaddi (PI: John Bushweller) 8
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