Masaoki Kawasumi
Assistant Professor
Division of Dermatology
Principal Investigator, Kawasumi Lab
Related Links: 
Kawasumi Lab
American Society for Photobiology (ASP)

Faculty Information

Biography

Dr. Masaoki Kawasumi is a photobiology and skin cancer researcher at the University of Washington in Seattle.  During medical school, Masaoki had the opportunity to work with Masafumi Nishizawa, PhD (Microbiology, Keio University), elucidating the regulation of cell cycle progression in yeast.  After graduating from Keio University School of Medicine, Dr. Kawasumi received PhD training in the neuroscience field (Dissertation Adviser: Ikuo Nishimoto, MD, PhD, Pharmacology, Keio University). He generated a knock-in mouse model for Alzheimer’s disease that recapitulated memory deficits analogous to those in humans. 

In 2004, Dr. Kawasumi joined Dr. Nghiem’s laboratory at Massachusetts General Hospital as a postdoctoral fellow. In 2006, Dr. Kawasumi moved from Boston to Seattle when Dr. Nghiem moved his laboratory to the University of Washington. Since then, Dr. Kawasumi has been conducting research in skin cancer biology, particularly addressing how cells respond to UV damage and how the DNA damage response can be harnessed to prevent UV-associated skin cancers, the most prevalent cancers in the U.S.  After completing postdoctoral work with Paul Nghiem, Dr. Kawasumi launched a research laboratory in 2016 at the University of Washington Dermatology.

The Kawasumi Lab focuses on elucidating molecular mechanisms of UV-mediated diseases (skin cancer and lupus). His research has been supported by the National Institutes of Health and Dermatology Foundation. 

Education & Training: 
PhD
Keio University Graduate School of Medicine
Tokyo Japan
2004
MD
Keio University Graduate School of Medicine
Tokyo Japan
1999
Honors: 
Annual Biomedical Research Conference for Minority Students (ABRCMS) Judge Travel Award (4 consecutive years)
2015-2018
University of Washington School of Medicine Excellence in Teaching
2017
Society for Investigative Dermatology (SID)/Albert M. Kligman Travel Fellowship Award
2019
Contact
Email: 
kawasumi@uw.edu
Phone: 
(206) 897-5456
Mailing Address: 

UW Medicine South Lake Union
850 Republican St, Brotman Rm 321
Box 358050
Seattle, WA 98109

Lab: 206-897-5440

Fax: 206-897-5442

Research & Clinical Interests
Research Interests: 
  • UV skin carcinogenesis  
  • DNA damage responses
  • UV-induced DNA lesions (CPD and 6-4PP)
  • DNA replication blockage at UV lesions
  • Replication checkpoint
  • Small-molecule inhibitors of the ATR-Chk1 pathway
  • Chromatin recruitment of the ATR activation complex
  • CRISPR-Cas9-based epigenome editing to inhibit skin cancer
  • Super-enhancers as epigenetic targets in skin cancer
  • Skin cancer disparities
  • Skin cancer prevention by caffeine 

Modulation of the replication checkpoint to combat UV carcinogenesis.
Ultraviolet (UV) from one-hour sunlight generates 100,000 DNA lesions per cell that are potentially mutagenic, leading to the most prevalent cancers in humans. Understanding how cells respond to UV-induced DNA lesions could be helpful to selectively kill DNA-damaged cells and prevent UV-associated skin cancers. Strikingly, multiple human epidemiological studies and mouse data demonstrated that caffeine suppresses UV-induced skin cancer development. We found that genetic inhibition of ATR, which is a pivotal kinase for surviving DNA damage, suppresses UV carcinogenesis, and this finding supports ATR inhibition as the relevant mechanism for the protective effect of caffeinated beverage intake.

Elucidation of mechanisms that respond to UV-induced DNA damage, especially ATR kinase pathway (replication checkpoint).
To better understand UV-induced DNA damage response, we recently dissected differential roles of two major types of UV-induced DNA lesions (cyclobutane pyrimidine dimers and 6-4 photoproducts) in ATR pathway activation and DNA replication blockage. This study provides insight into potential mechanisms by which caffeine inhibits mutation incorporation following UV irradiation.

Chemical genetic approach to discover novel small-molecule inhibitors of DNA damage response.
To discover druggable targets in the ATR pathway, we performed a phenotype-based screen of 9,195 small-molecule compounds and identified four compounds that inhibit the ATR pathway but are mechanistically distinct from typical ATR kinase catalytic inhibitors. This study highlights the complexity of the ATR pathway, and these novel ATR pathway inhibitors can be used to further elucidate druggable mechanisms in order to improve cancer therapy.

Keywords: 

UV skin carcinogenesis 

Skin cancer prevention by caffeine

DNA damage responses
UV-induced DNA lesions (CPD and 6-4PP)
DNA replication blockage at UV lesions
Replication checkpoint
Small-molecule inhibitors of the ATR-Chk1 pathway
Chromatin recruitment of the ATR activation complex

Publications
PubMed: 
PubMed Bibliography
Publications: 

Selected Publications

Hung KF, Sidorova JM, Nghiem P, Kawasumi M. The 6-4 photoproduct is the trigger of UV-induced replication blockage and ATR activation. Proc Natl Acad Sci USA. 2020;117:12806-16. PMID: 32444488

Lee JW, Ratnakumar K, Hung KF, Rokunohe D, Kawasumi M. Deciphering UV-induced DNA Damage Responses to Prevent and Treat Skin Cancer. Photochem Photobiol. 2020;96:478-99. PMID: 32119110

Kawasumi M, Bradner JE, Tolliday N, Thibodeau R, Sloan H, Brummond KM, Nghiem P. Identification of ATR-Chk1 pathway inhibitors that selectively target p53-deficient cells without directly suppressing ATR catalytic activity. Cancer Res. 2014;74:7534-45. PMID: 25336189

Kawasumi M, Lemos B, Bradner JE, Thibodeau R, Kim YS, Schmidt M, Higgins E, Koo SW, Angle- Zahn A, Chen A, Levine D, Nguyen L, Heffernan TP, Longo I, Mandinova A, Lu YP, Conney AH, Nghiem P. Protection from UV-induced skin carcinogenesis by genetic inhibition of the ataxia telangiectasia and Rad3-related (ATR) kinase. Proc Natl Acad Sci USA. 2011;108:13716-21. PMID: 21844338

Huryn DM, Brodsky JL, Brummond KM, Chambers PG, Eyer B, Ireland AW, Kawasumi M, Laporte MG, Lloyd K, Manteau B, Nghiem P, Quade B, Seguin SP, Wipf P. Chemical methodology as a source of small-molecule checkpoint inhibitors and heat shock protein 70 (Hsp70) modulators. Proc Natl Acad Sci USA. 2011;108:6757-62. PMID: 21502524

Heffernan TP, Kawasumi M, Blasina A, Anderes K, Conney AH, Nghiem P. ATR-Chk1 pathway inhibition promotes apoptosis after UV treatment in primary human keratinocytes: potential basis for the UV protective effects of caffeine. J Invest Dermatol. 2009;129:1805-15. PMID: 19242509 [* Co-first authors]