Research center funded by NIH award

The statistics are staggering: Kentucky has disproportionately high incidences of both cancer and metabolic disorders – leading the nation in cancer deaths and ranking in the Top 10 for highest obesity rates in the country. While scientists have long known of a direct link between obesity and cancer, the need for further research has become a priority in the interest of keeping Kentuckians healthy.

This need is being answered by the UK Center for Cancer and Metabolism, or CCM. Led by Daret St.Clair, PhD, and Binhua “Peter” Zhou, PhD, the CCM harnesses UK’s institutional strengths in cancer and advanced metabolomics tools to focus on the underlying mechanisms linking dysfunctional metabolism to cancer.

The CCM is funded by a prestigious Centers of Biomedical Research Excellence (COBRE) grant from the National Institutes of General Medical Sciences, part of the National Institutes of Health. The $11.2 million grant, awarded in April 2017, will fund the CCM over the next five years.

The COBRE grant and establishment of the CCM has put UK researchers in an excellent position to discover scientific breakthroughs that could yield potentially life-saving treatments for people across Kentucky.

UK Markey Cancer Center Director B. Mark Evers, MD, said the CCM is instrumental in Markey’s fight against cancer in the Commonwealth.

“Nowhere in the country is it more important to have this level of cancer research underway,” Evers said. “Kentuckians face a unique set of health issues, but Markey is distinctly positioned to help solve the problem. Being a National Cancer Institute-designated cancer center means being a leader in research as well as clinical care and outreach. This funding will allow us to translate our findings into potential new therapies for cancer patients from Kentucky and beyond.”

Making strides in cancer metabolism research

In the CCM, four junior investigators, mentored by teams of clinicians and scientists from a variety of disciplines, departments and colleges at UK, each lead major projects investigating an aspect of cancer metabolism.

“The Center for Cancer and Metabolism helps UK researchers to identify the mechanism underlying the dysregulation of metabolism and cancer development,” Zhou said. “Ultimately, this line of investigation will lead to development of innovative therapeutics to prevent cancer for the benefit of patients and their families in Kentucky.”

Each CCM project leads investigators into new territory to develop exciting new treatments. Travis Thomas, PhD; Yadi Wu, PhD; Ren Xu, PhD; and Kate Zaytseva, PhD, were the CCM’s first group of investigators, with Xu “graduating” from the program in the summer of 2017 after receiving independent grant funding to continue his research.

Thomas is analyzing the role of vitamin D in protecting patients against muscle wasting. To fight basal-like breast cancer, Wu is studying serine biosynthesis pathways to develop an effective therapy combining metabolic drugs and epigenetic inhibitors, which slow cancer’s development. And Zaytseva is developing selective therapies to prevent or reduce colorectal cancer metastasis, the leading cause of death from colorectal cancer-related tumors.

To replace Xu’s project, Luksana Chaiswing, PhD, was selected to join the CCM as a project lead investigator studying radiation-resistant prostate cancer, aiming to enhance radiation therapy as a more effective procedure.

Creating a culture of collaboration

Xu’s project focused on defining the role of RORα in suppressing breast cancer progression and metastasis. Thanks to Xu’s role in the CCM and the support of his mentors, his findings were published in the Journal of Cell Science, and an R01 grant proposal based on the project was funded by the NCI.

“The CCM provided substantial help in generating preliminary data, developing the proposal and preparing the application,” Xu said. “In fact, Drs. St. Clair and Andrew Lane are co-investigators on my R01 application.”

That kind of collaboration is exactly why the CCM was an appealing recipient of the COBRE grant, St. Clair said. Earning COBRE grant funding is intensely competitive, both institutionally and nationally. After nearly a year of preparation, UK’s submission was reviewed in June 2016. Upon review, it received a nearly perfect score and was among the leading submissions received for review in 2016.

“Having the kind of environment where learning and collaboration are placed at the forefront is why we were chosen for this grant, and we hope to continue that throughout the life of this center,” St. Clair said.

“It will also enable us to reach out to new and talented researchers who want to come to UK to become new project leaders and continue the work we’re doing.”