Mazhar Adli

Education

  • PhD, University of North Carolina at Chapel Hill
  • MSc, Sabanci University
  • Postdoc, Harvard Medical School, Mass general Hosptal, Broad Institute of Harvad and MIT

Primary Appointment

  • Assistant Professor, Biochemistry and Molecular Genetics

Contact

Research Interest(s)

Identify and target key genomic and epigenomic drivers in cancer

Research Description

Main Goal: Identify and target key genomic and epigenomic drivers in cancer

Main Tools: CRISPR-based Genome & Epigenome editing, Genome scale CRISPR-screening, Live cell chromatin imaging, ChIP-Seq, ATAC-Seq, RNA-Seq, single cell RNA-Seq

Our ultimate research goal to understand key drivers of cancerous cellular state and identify therapeutic vulnerabilities for novel drug combinations to prevent cancer development and chemotherapy resistance. To achieve this goal, our lab is using genomic and epigenomic mapping, editing and imaging approaches to understand genome regulation in normal and malignant settings. We also use computation approaches to integrate large scale-genomic data and utilize experimental tools and technologies to understand and prevent aberrant genome regulation in disease, specifically cancer.

Our laboratory is utilizing and also developing cutting-edge functional genomics strategies and developing novel CRISPR based manipulation tools to understand dynamic gene regulation and 3D genome organization in normal and malignant settings. These efforts are based on our previous expertise in cancer research, genome-wide approaches, and development of novel technologies. During his postdoctoral training at Harvard Medical School and the Broad Institute, Dr. Adli established unique technical and analytical expertise in genomics and epigenomic profiling and computational data analysis. During this process, he developed the Nano-ChIP-Seq technology that overcomes the cell number limitation of conventional ChIP-Seq technology (Nature Methods, 2010; Nature Protocols, 2011) and played critical roles in multiple large-scale projects including Roadmap Epigenome Mapping Consortium (Cell, 2013) and cancer genome projects (Nature 2012, Cancer Cell 2012, NEJM 2013). Currently, the Adli lab is combining genome and epigenome mapping expertise with novel CRISPR-based manipulation tools to achieve our ultimate research goals. To this end, we have developed a strong expertise in CRISPR technologies (Nature Communications 2018; Nature Methods 2016; Nature Biotechnology 2014; NAR, 2015). We are actively developing and utilizing novel CRISPR tools to edit genome, manipulate epigenome and image live cells chromatin dynamics in living cells (Nature Methods, 2017, Nature Communications, 2017). These functional genomic tools combined with our capacity to analyze and integrate large-scale data analysis enables us to set rigorous and ambitious research goals and achieve them faster.

Main Research Projects in the Adli Lab:

Project #1: Characterizing therapy induced epigenetic alterations that drive chemoresistance in High Grade Serous Ovarian Cancer

Project #2: Genome-scale CRISPR KO screening in pancreatic cancer to identify novel tumor suppressors and combinatorial synthetic lethal drug targets

Project #3: Develop novel CRISPR-based tools for epigenome editing and chromatin engineering in living cells

Project 4: Identify functional roles and target recurrent non-coding mutations in cancer

Selected Publications

  • Kuscu C, Parlak M, Tufan T, Yang J, Szlachta K, Wei X, Mammadov R, Adli M. CRISPR-STOP: gene silencing through base-editing-induced nonsense mutations. Nature methods. 2017;14(7): 710-712. PMID: 28581493
  • Qin P, Parlak M, Kuscu C, Bandaria J, Mir M, Szlachta K, Singh R, Darzacq X, Yildiz A, Adli M. Live cell imaging of low- and non-repetitive chromosome loci using CRISPR-Cas9. Nature communications. 2017;8 14725. PMID: 28290446 | PMCID: PMC5424063
  • Ataman B, Boulting G, Harmin D, Yang M, Baker-Salisbury M, Yap E, Malik A, Mei K, Rubin A, Spiegel I, Durresi E, Sharma N, Hu L, Pletikos M, Griffith E, Partlow J, Stevens C, Adli M, Chahrour M, Sestan N, Walsh C, Berezovskii V, Livingstone M, Greenberg M. Evolution of Osteocrin as an activity-regulated factor in the primate brain. Nature. 2016;539(7628): 242-247. PMID: 27830782 | PMCID: PMC5499253
  • Illendula A, Gilmour J, Grembecka J, Tirumala V, Boulton A, Kuntimaddi A, Schmidt C, Wang L, Pulikkan J, Zong H, Parlak M, Kuscu C, Pickin A, Zhou Y, Gao Y, Mishra L, Adli M, Castilla L, Rajewski R, Janes K, Guzman M, Bonifer C, Bushweller J. Small Molecule Inhibitor of CBFβ-RUNX Binding for RUNX Transcription Factor Driven Cancers. EBioMedicine. 2016;8 117-31. PMID: 27428424 | PMCID: PMC4919611
  • Kuscu C, Adli M. CRISPR-Cas9-AID base editor is a powerful gain-of-function screening tool. Nature methods. 2016;13(12): 983-984. PMID: 27898061
  • Adli M, Parlak M, Li Y, El-Dahr S. Epigenetic States of nephron progenitors and epithelial differentiation. Journal of cellular biochemistry. 2015;116(6): 893-902. PMID: 25560433 | PMCID: PMC4511265
  • Anderson C, Clark D, Adli M, Kendall M. Correction: Ethanolamine Signaling Promotes Salmonella Niche Recognition and Adaptation during Infection. PLoS pathogens. 2015;11(12): e1005365. PMID: 26684793 | PMCID: PMC4684284
  • Kundaje A, Meuleman W, Ernst J, Bilenky M, Yen A, Heravi-Moussavi A, Kheradpour P, Zhang Z, Wang J, Ziller M, Amin V, Whitaker J, Schultz M, Ward L, Sarkar A, Quon G, Sandstrom R, Eaton M, Wu Y, Pfenning A, Wang X, Claussnitzer M, Liu Y, Coarfa C, Harris R, Shoresh N, Epstein C, Gjoneska E, Leung D, Xie W, Hawkins R, Lister R, Hong C, Gascard P, Mungall A, Moore R, Chuah E, Tam A, Canfield T, Hansen R, Kaul R, Sabo P, Bansal M, Carles A, Dixon J, Farh K, Feizi S, Karlic R, Kim A, Kulkarni A, Li D, Lowdon R, Elliott G, Mercer T, Neph S, Onuchic V, Polak P, Rajagopal N, Ray P, Sallari R, Siebenthall K, Sinnott-Armstrong N, Stevens M, Thurman R, Wu J, Zhang B, Zhou X, Beaudet A, Boyer L, De Jager P, Farnham P, Fisher S, Haussler D, Jones S, Li W, Marra M, McManus M, Sunyaev S, Thomson J, Tlsty T, Tsai L, Wang W, Waterland R, Zhang M, Chadwick L, Bernstein B, Costello J, Ecker J, Hirst M, Meissner A, Milosavljevic A, Ren B, Stamatoyannopoulos J, Wang T, Kellis M. Integrative analysis of 111 reference human epigenomes. Nature. 2015;518(7539): 317-30. PMID: 25693563 | PMCID: PMC4530010
  • Kuntimaddi A, Achille N, Thorpe J, Lokken A, Singh R, Hemenway C, Adli M, Zeleznik-Le N, Bushweller J. Degree of recruitment of DOT1L to MLL-AF9 defines level of H3K79 Di- and tri-methylation on target genes and transformation potential. Cell reports. 2015;11(5): 808-20. PMID: 25921540 | PMCID: PMC4426023
  • Qin F, Song Z, Babiceanu M, Song Y, Facemire L, Singh R, Adli M, Li H. Correction: discovery of CTCF-sensitive cis-spliced fusion RNAs between adjacent genes in human prostate cells. PLoS genetics. 2015;11(4): e1005161. PMID: 25860022 | PMCID: PMC4393099
  • Singh R, Kuscu C, Quinlan A, Qi Y, Adli M. Cas9-chromatin binding information enables more accurate CRISPR off-target prediction. Nucleic acids research. 2015. PMID: 26032770 | PMCID: PMC4605288
  • 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;32(7): 677-83. PMID: 24837660
  • Rissman E, Adli M. Minireview: transgenerational epigenetic inheritance: focus on endocrine disrupting compounds. Endocrinology. 2014;155(8): 2770-80. PMID: 24885575 | PMCID: PMC4098001
  • Abdel-Wahab O, Gao J, Adli M, Dey A, Trimarchi T, Chung Y, Kuscu C, Hricik T, Ndiaye-Lobry D, Lafave L, Koche R, Shih A, Guryanova O, Kim E, Li S, Pandey S, Shin J, Telis L, Liu J, Bhatt P, Monette S, Zhao X, Mason C, Park C, Bernstein B, Aifantis I, Levine R. Deletion of Asxl1 results in myelodysplasia and severe developmental defects in vivo. The Journal of experimental medicine. 2013;210(12): 2641-59. PMID: 24218140 | PMCID: PMC3832937
  • Zhu J, Adli M, Zou J, Verstappen G, Coyne M, Zhang X, Durham T, Miri M, Deshpande V, De Jager P, Bennett D, Houmard J, Muoio D, Onder T, Camahort R, Cowan C, Meissner A, Epstein C, Shoresh N, Bernstein B. Genome-wide chromatin state transitions associated with developmental and environmental cues. Cell. 2013;152(3): 642-54. PMID: 23333102 | PMCID: PMC3563935
  • Koppikar P, Bhagwat N, Kilpivaara O, Manshouri T, Adli M, Hricik T, Liu F, Saunders L, Mullally A, Abdel-Wahab O, Leung L, Weinstein A, Marubayashi S, Goel A, Gönen M, Estrov Z, Ebert B, Chiosis G, Nimer S, Bernstein B, Verstovsek S, Levine R. Heterodimeric JAK-STAT activation as a mechanism of persistence to JAK2 inhibitor therapy. Nature. 2012. PMID: 22820254 | PMCID: 22820254
  • Adli M, Bernstein B. Whole-genome chromatin profiling from limited numbers of cells using nano-ChIP-seq. Nature protocols. 2011;6(10): 1656-68. PMID: 21959244 | PMCID: 21959244
  • Chapman M, Lawrence M, Keats J, Cibulskis K, Sougnez C, Schinzel A, Harview C, Brunet J, Ahmann G, Adli M, Anderson K, Ardlie K, Auclair D, Baker A, Bergsagel P, Bernstein B, Drier Y, Fonseca R, Gabriel S, Hofmeister C, Jagannath S, Jakubowiak A, Krishnan A, Levy J, Liefeld T, Lonial S, Mahan S, Mfuko B, Monti S, Perkins L, Onofrio R, Pugh T, Rajkumar S, Ramos A, Siegel D, Sivachenko A, Stewart A, Trudel S, Vij R, Voet D, Winckler W, Zimmerman T, Carpten J, Trent J, Hahn W, Garraway L, Meyerson M, Lander E, Getz G, Golub T. Initial genome sequencing and analysis of multiple myeloma. Nature. 2011;471(7339): 467-72. PMID: 21430775 | PMCID: NIHMS385546
  • Adli M, Merkhofer E, Cogswell P, Baldwin A. IKKalpha and IKKbeta each function to regulate NF-kappaB activation in the TNF-induced/canonical pathway. PloS one. 2010;5(2): e9428. PMID: 20195534 | PMCID: PMC2828475
  • Adli M, Zhu J, Bernstein B. Genome-wide chromatin maps derived from limited numbers of hematopoietic progenitors. Nature methods. 2010;7(8): 615-8. PMID: 20622861 | PMCID: PMC2924612
  • Goren A, Ozsolak F, Shoresh N, Ku M, Adli M, Hart C, Gymrek M, Zuk O, Regev A, Milos P, Bernstein B. Chromatin profiling by directly sequencing small quantities of immunoprecipitated DNA. Nature methods. 2009;7(1): 47-9. PMID: 19946276 | PMCID: PMC2862482
  • Ku M, Koche R, Rheinbay E, Mendenhall E, Endoh M, Mikkelsen T, Presser A, Nusbaum C, Xie X, Chi A, Adli M, Kasif S, Ptaszek L, Cowan C, Lander E, Koseki H, Bernstein B. Genomewide analysis of PRC1 and PRC2 occupancy identifies two classes of bivalent domains. PLoS genetics. 2008;4(10): e1000242. PMID: 18974828 | PMCID: PMC2567431
  • Dan H, Adli M, Baldwin A. Regulation of mammalian target of rapamycin activity in PTEN-inactive prostate cancer cells by I kappa B kinase alpha. Cancer research. 2007;67(13): 6263-9. PMID: 17616684 | PMCID: 17616684
  • Adli M, Baldwin A. IKK-i/IKKepsilon controls constitutive, cancer cell-associated NF-kappaB activity via regulation of Ser-536 p65/RelA phosphorylation. The Journal of biological chemistry. 2006;281(37): 26976-84. PMID: 16840782 | PMCID: 16840782