School of Medicine

Graduate Student Ryan Davis Studies Tumor Cells for Answers to Metastatic Breast Cancer

Graduate Student Ryan Davis
Graduate Student Ryan Davis

June 3, 2020

Metastasis is the number one cause of most mortality associated with breast cancer, responsible for killing as many as 40,000 American women each year. Graduate student Ryan Davis aims to lower that number. His team’s recent research finding, reported in Nature Cell Biology in March, with Davis as first author, shows he is headed in a promising direction.

“Breast cancer is the most common and second deadliest of all cancers for women,” says Davis. “We have to stop it. Metastasis is key to this problem. Compared to someone with a localized tumor, whose five-year survival rate can exceed 97 percent, the five-year survival rate someone with metastatic disease is 30 percent or worse.”

Davis, who is in within months of completing his doctorate in biomedical sciences, entered UCI as a biology major, planning to become a physician.

In his junior year, he participated in the Undergraduate Research Opportunities Program, which introduces students to the UCI research culture as they develop research and creative skills, with support from faculty mentors.  Working in the lab of Yongsheng Shi, PhD, Professor, Microbiology & Molecular Genetics School of Medicine and current Chancellor’s fellow, he became involved in RNA research.

“There, in his lab, I was exposed to a whole other side of medicine—where people are really developing the future treatments for patients,” says Davis.

He abandoned the idea of becoming a physician. Instead, he would seek to save and improve lives through scientific research.

In 2016, Davis became one of the first graduate students to join the lab of a new UCI School of Medicine researcher, Assistant Professor Devon Lawson, PhD.

Lawson’s lab in the Department of Physiology and Biophysics explores the cellular and molecular mechanisms underlying the metastatic spread of cancer cells to peripheral tissues. It is where Davis’s journey to understand metastasis began.

Although breast cancer surgery can effectively treat localized disease, it is still possible for microscopic cells from the tumor to escape undetected and travel to lymph nodes, lungs or other parts of the body, where they grow to threaten the health of their host months or years later. Davis is studying how these micrometastatic tumor cells differ from primary tumor cells in breast cancer patients and why these cells thrive.

His timing is good. Only in the last decade has single-cell sequencing technology made it possible to view and analyze individual cancer cells at an unprecedented level of detail.

Davis ultimately generated and analyzed a library of more than 1500 cells. As the research team reported in Nature Cell Biology, the investigation showed that micrometastatic cancer cells preferentially shift their metabolism towards mitochondrial oxidative phosphorylation. Blocking this metabolic process could prevent the cells from being able to spread and metastasize, ultimately leading to therapeutics that prevent metastasis.

“Ryan’s rapid progress on his research project is remarkable, given that he had to learn challenging bioinformatics, statistics, and computational biology skills in order to analyze the large and complex single-cell datasets,” says Lawson.

Co-mentor David Fruman, PhD, Professor of Molecular Biology and Biochemistry and Associate Director of the UCI Cancer Research Institute, says Davis’s technical mastery was instrumental to his project.  He describes Davis as “an original thinker with a broad knowledge base, capable of sorting through complex datasets to identify important biology.”

Davis has received several noteworthy fellowships to support his work including the Center for Complex Biological Systems Opportunity Award, the T32 Cancer Biology and Therapeutics Training Grant and the Gazzaniga Family Medical Research Award. The Gazzaniga Family Research Award was established with support from retired UCI cardiothoracic surgeon Dr. Alan Gazzaniga. It is presented annually to a graduate student like Davis, with outstanding academic credentials and a promising biomedical study underway.  

“Grad students, myself included, we become very invested in our specialized field, and we often miss out on new perspectives from outside our field,” says Davis. “Awards like Dr. Gazzaniga’s make it possible to travel to conferences to hear scientific leaders around the world talk about what going on outside my area…and see connections to my work—maybe spark other ideas for things I can do.”

The award also gave Davis additional resources to advance to the next step in his research—investigating the point in the metastatic process at which the metabolic switch is activated. For now, his lab research is on pause due to COVID-19. Depending upon when UCI labs open, his plan is to finish this summer.

Then, it’s on to a postdoctoral position, ideally in cancer immunotherapy. He hopes to integrate all he has learned about cancer metabolism with new knowledge of immunotherapy to generate original insights that help to solve medical mysteries.