Research Description

My team and I in the Kawasumi Lab are specifically focused on the molecular mechanisms of UV-induced DNA damage responses and skin carcinogenesis. Our aim is to improve the prevention and treatment of cutaneous squamous cell carcinoma (cSCC) and melanoma.

UV radiation is the most prevalent carcinogen in humans, responsible for more than five million skin cancer cases annually in the United States. UV exposure induces both genetic mutations and epigenetic abnormalities that affect the expression of cancer-relevant genes, but how these epigenetic changes contribute to skin malignancies remains unclear.

Using CRISPR-Cas9-based genome and epigenome editing tools, the Kawasumi Lab aims to elucidate the role of epigenetic abnormalities in malignant transformation, with the goal of developing novel therapeutic strategies to target epigenetic aberrations and inhibit cSCC. I have been awarded a National Cancer Institute R01 grant to support this research project.

My previous research included a project focused on how cells sense UV damage. UV radiation induces over 100,000 DNA lesions per cell after just one hour of sun exposure, many of which can be mutagenic. UV radiation damages DNA by forming dimers at dipyrimidine sites. There are two major types of UV-induced DNA lesions: cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts (6-4PPs). However, it remained unclear which type of lesion activates the ATR-Chk1 signaling, a pivotal pathway that senses UV damage and regulates the cell cycle and DNA repair, maintaining genome integrity. We revealed that only 6-4PP, but not CPD, triggers DNA replication blockage and ATR activation.

Another project explored how caffeine can help prevent UV-induced skin carcinogenesis. We were inspired to investigate this topic because multiple human epidemiological studies demonstrate that caffeinated coffee intake is associated with decreased risks of developing skin cancer. However, molecular mechanisms by which caffeine suppresses UV-induced skin carcinogenesis remained elusive. Caffeine has many cellular targets, including the ATR kinase that elicits replication checkpoint and promotes survival of damaged cells. We found that genetic inhibition of the ATR kinase suppresses UV carcinogenesis by augmenting UV-induced apoptosis. We also discovered novel small-molecule inhibitors of the ATR pathway that can sensitize p53-deficient cells to DNA-damaging agents. Given the high prevalence of skin cancer and the popularity of coffee, these findings suggest that caffeine may offer a broadly accessible means of cancer prevention. Our studies provide new molecular insights into this protective effect, connecting fundamental mechanisms with population health.

My responsibilities include helping to educate the next generation of scientists. I completed training through the Center for the Improvement of Mentored Experiences in Research, and am now a facilitator for both research mentor and mentee training, with a strong interest in research education for graduate students.

I am actively involved with the American Society for Photobiology, and have been honored to receive the organization’s New Investigator Award and Presidential Service Award. I also serve as an associate editor for the peer-reviewed journal Photodermatology, Photoimmunology & Photomedicine.