April 16, 2019

Justin W. Leung, Ph.D.

Assistant Professor
Department of Radiation Oncology
Biochemistry and Molecular Biology (secondary appointment)
UAMS College of Medicine

Research Interest Statement

Tens of thousands of DNA damages occur per cell per day from endogenous metabolites, environmental and dietary carcinogens. It can threaten our genome integrity and promote tumor progression. To deal with this genotoxic challenge, our body has evolved an intricate defense mechanism, the DNA damage response (DDR) pathway, to maintain the genome stability. The DDR pathway is essential for normal development, cellular homeostasis, and tumor suppression. It relies on the precise orchestration of DNA replication, chromosome segregation, DNA repair and genome surveillance mechanisms.

Our lab is focused on the exploration of the causes and effects of genome instability and the mechanism of DNA repair. More specifically, we investigate how cells detect, signal and repair DNA damage in eukaryotes. We use genetics, biochemical, proteomics and cell-based assays to understand how cells protect our genome integrity. Our long-term goals are to define the chromatin-based DDR pathway, its regulatory mechanism and potentially discover a new therapeutic strategy to target cancer cells. Our current projects aim to dissect the underlying mechanism of how BRCA1-mediated DNA repair machinery is executed at the right place and the right time through chromatin modifications. These works will uncover the molecular mechanism in BRCA1 regulation and build a foundation for translational research in breast cancer.

Grants

NIH NCI K22 career development award

1/1/2018-12/31/2020

$166,100*

*cancer-related annual direct costs

Dr. Leung’s UAMS Collaborators

Fen Xia, M.D., Ph.D.

Gunnar Boysen, Ph.D.

Kevin Raney, Ph.D.

Robert Eoff, Ph.D.

Robert Griffin, Ph.D.

Rupak Pathak, Ph.D.

Dr. Leung’s External Collaborators

Dr. Jiadong Wang, Ph.D. (University of Beijing)

Dr. Jeffrey Dick, Ph.D. (University of North Carolina)

Dr. Gargi Ghosal, Ph.D. (University of Nebraska Medical Center)

Dr. Qingou Gong, Ph.D. (University of Science and Technology of China)

Dr. Michael Huen, Ph.D. (University of Hong Kong)

Dr. Wenqi Wang, Ph.D. (UC Irvine)

Opportunities for Collaboration

I am interested in studying chromatin biology, genome editing and DNA repair, but I also welcome collaborations on any interesting scientific topic.

You Might Not Know That …

I love coffee, and I roast coffee beans when I have free time. Stop by my lab if you want to try some.

Cancer-Related Publications

  • West KL, Kelliher JL, Xu Z, An L, Reed MR, Eoff RL, Wang J, Huen MS, Leung JW. LC8/DYNLL1 is a 53BP1 effector and regulates checkpoint activation. Nucleic Acid Research. In Press
  • Makharashvili N, Arora S, Yin Y, Fu Q, Leung JW, Miller KM, Paull TT. Sae2/CtIP prevents R-loop accumulation in eukaryotic cells. Elife. 2018; 7:e42733.
  • Leung JW, Emery LE, Miller KM. CRISPR/Cas9 gene editing of human histone H2A variants H2AX and macroH2A. Methods in Molecular Biology. 2018; 1832:255-269.
  • Leung JW, Makharashvili N, Agarwal P, Pourpre R, Cammarata M, Cannon J, Sherker A, Durocher D, Brodbelt J, Paull TT & Miller KM. ZMYM3 regulates BRCA1 localization at damaged chromatin to promote DNA repair. Genes and Development, 2017 Feb; 31:260-274.
  • Gong F, Chiu L, Cox B, Aymard F, Clouaire T, Leung JW, Cammarata M, Perez M, Agarwal P, Brodbelt JS, Legube G & Miller KM. Screen identifies bromodomain protein ZMYND8 in chromatin recognition of transcription-associated DNA damage that promotes homologous recombination. Genes & Development. 2015 Jan;29(2):197-211.
  • Huang Y, Leung JW, Lowery M, Matsushita N, Wang Y, Shen X, Huong D, Takata M, Chen J, Li L. Modularized functions of the Fanconi anemia core complex. Cell Reports. 2014 Jun 26;7(6):1849-57.
  • Leung JW, Agarwal P, Canny MD, Gong, Robison AD, Finkelstein IJ, Durocher D & Miller KM. Nucleosome acidic patch promotes RNF168- and RING1B/BMI1-dependent H2AX and H2A ubiquitination and DNA damage signaling. PLoS Genetics, 2014 Mar 6;10(3):e1004178.
  • Wang Y, Han X, Wu F, Leung JW, Lowery MG, Do H, Chen J, Shi C, Tian C, Li L, Gong W. Structure analysis of FAAP24 reveals single-stranded DNA-binding activity and domain functions in DNA damage response. Cell Research. 2013 Oct; 23(10):1215-28.
  • Wang Y, Leung JW, Jiang Y, Lowery MG, Do HG, Vasquez KM, Chen K, Wang W, Li L. Functional divergence of Fanconi anemia genes. The FASEB Journal. 2013 Apr; 27:451.3
  • Leung JW, Ghosal G, Wang W, Shen X, Li L, Chen J. Alpha thalassemia/mental retardation syndrome X-linked gene product ATRX is required for proper replication restart and cellular resistance to replication stress. Journal of Biological Chemistry. 2013 Mar 1;288(9):6342-50.
  • Wang Y, Leung JW, Jiang Y, Lowery MG, Vasquez KM, Chen J, Wang W, Li L. FANCM and FAAP24 maintain genomic stability through cooperative as well as unique functions. Molecular Cell. 2013 Mar 7;49(5):997-1009.
  • Wang J, Leung JW, Gong Z, Shi X, Chen J. PHF6 regulates cell cycle progression by suppressing ribosomal RNA synthesis. Journal of Biological Chemistry, 2013 Feb 1; 288 (5):3714-83.
  • Fong KW, Leung JW, Li Y, Wang W, Ling F, Ma W, Liu Dan, Zhou S, Chung J. MTR120/KIAA1383, a novel microtubule-associated protein, promotes microtubule stability and ensures cytokinesis. Journal of Cellular Science. 2013 Feb 1;126(Pt 3):825-37.
  • Ghosal G, Leung JW, Nair BC, Chen J. PCNA-binding protein C1orf124 is a regulator of translesion synthesis. Journal of Biological Chemistry, 2012 Oct 5;287(41):34225-33.
  • Leung JW, Wang Y, Fong KW, Huen MS, Li L, Chen J. Fanconi anemia (FA) binding protein FAAP20 stabilizes FA complementation group A (FANCA) and participates in interstrand cross-link repair. Proceeding of the National Academy of Sciences.2012 Mar 20;109(12):4491-6.
  • Leung JW, Leitch A, Wood JL, Shaw-Smith C, Metcalfe K, Bicknell LS, Jackson AP, Chen J. SET nuclear oncogene associates with microcephalin/MCPH1 and regulates chromosome condensation. Journal of Biological Chemistry. 2011 Jun 17;286(24):21393-400.
  • Huen MS, Huang J, Leung JW, Sy SM, Leung KM, Ching YP, Tsao SW, Chen J. Regulation of chromatin architecture by the PWWP domain-containing DNA damage-responsive factor EXPAND1/MUM1. Molecular Cell. 2010 Mar 26;37(6):854-64.
  • Richards MW, Leung JW, Roe SM, Li K, Chen J, Bayliss R. A pocket on the surface of the N-terminal BRCT domain of MCPH1 is required to prevent abnormal chromosome condensation. Journal of Molecular Biology. 2010 Feb 5;395(5):908-15.