Apr 01, 2021 10:00 AM

Read Time: 6 minutes

Members of the USPORE team- Martin McMahon PhD, Sheri Holmen, PhD, Douglas Grossman, MD, PhD
Huntsman Cancer Institute (HCI) is committed to providing an atmosphere where ideas can be created, cultivated, and shared. When cancer researchers from different disciplines work together, they gain new insights from each other’s expertise into how cancer develops and how it can be targeted. Here are some of the collaborations from HCI scientists that are accelerating progress in cancer research.

Improving Melanoma Prevention and Treatment through Collaborative Research

In order to support collaborative cancer research and bring innovative treatments to patients more quickly, the National Cancer Institute established Specialized Programs of Research Excellence (SPOREs). Each SPORE involves scientists from the lab and the clinic who work together on the same cancer type or theme.

The aspiring SPORE team at Huntsman Cancer Institute (HCI) at the University of Utah (U of U), known as USPORE, focuses on melanoma and includes investigators from U of U basic science and clinical departments who meet on a weekly basis as part of the Melanoma Disease Center at HCI. USPORE builds on the strengths of established, ongoing, collaborative scientific and clinical investigations within U of U and HCI, with the long-term goal of contributing to melanoma prevention and treatment strategies.

Melanoma is the leading cause of cancer death in young women ages 25–30, and Utah has the most cases, per capita, in the United States.

"I have dedicated my career to furthering our understanding of melanoma so therapies can be developed to improve outcomes for these women, who are in the prime of their lives," says Sheri L. Holmen, PhD, co-leader of both the Cell Response and Regulation Program and the Melanoma Disease Center.

The research team has identified three short-term goals for this research. The first project will evaluate the potential UV-protective effects of aspirin in mice and humans at high risk for melanoma. The second project will focus on developing the best dosing schedule to prevent drug resistance in melanoma patients with a mutation of the BRAF gene. Finally, the third project will look for a way to improve melanoma immunotherapy and investigate brain metastases.

The USPORE team received funding for the first project from a Department of Defense team science award, and the third project was funded by an NIH R21 grant and NIH R01 grant. The team will propose new projects for SPORE funding in the near future.

“We are confident our USPORE team will build on an outstanding history and foundation of melanoma research at the U of U and HCI, leading to new research insights and improvements in the prevention, prognosis, and treatment of melanoma,” Holmen adds.

bruce edgar
Bruce Edgar, PhD

Merging Metabolism Research with Stem Cell Biology to Understand Colon Cancer

Showing the importance of collaboration, a group of researchers at Huntsman Cancer Institute (HCI) studying metabolism and another exploring stem cell biology converged to create the gut stem cell team. The team studies the metabolism of intestinal stem cells in mice, fruit flies, and humans, with a focus on how it alters the way stem cells multiply and differentiate.

The team’s hypothesis is that stem cells in the gut are unique from other cells. The metabolism of these stem cells shares characteristics with the metabolism of gastrointestinal (GI) cancer cells.

“Intestinal stem cells give rise to colon cancer, and we believe alterations in their metabolism contributes to cancer development and progression. We aim to figure out precisely how by addressing different types of metabolism, analyzing stem cells in detail, and discovering and analyzing the genes that regulate metabolism in stem cells and tumors,” says Bruce Edgar, PhD. He serves as a project leader along with Jared Rutter, PhD, Scott Summers, PhD, and Dean Tantin, PhD.

The four project leaders each have a different area to analyze. Rutter’s group examines carbohydrate metabolism, Summers’s inspects fats and lipids, Tantin’s studies amino acids, and Edgar’s probes how epidermal growth factor signaling affects metabolism.

“This collaboration has generated a lot of synergy,” Edgar says. “Three groups are specialists in mice genetics. I am not. The others depend on my group for expertise in flies. Sheetal Hardikar, PhD, MBBS, and Ellen J. Beswick, PhD, are our experts on human gastrointestinal diseases; James Cox, PhD; is our dedicated metabolism expert; Beatrice Knudsen, MD, PhD; is our histology and imaging specialist; and there are many others. We have all learned different aspects of metabolism and that speaks to the collaborative nature at HCI.”

The team submitted a P01 grant to the National Cancer Institute in January 2021. The proposal investigates how intestinal stem cell metabolism impacts stem cell function during gut homeostasis, regeneration, and tumor development. The goal of the project is to identify new nutritional, medicinal, and genetic approaches for the prevention, diagnosis, and treatment of GI cancers.

katie ullman and colleague in lab
Katie Ullman, PhD, and Dollie LaJoie

Joining Together to Understand How Cells Divide

Cancer happens when cells divide uncontrollably and spread into surrounding tissues. Researchers at Huntsman Cancer Institute (HCI) from different specialties have teamed up with each other and with investigators outside HCI to better understand cell division pathways—the set of actions that lead to changes in the cell.

“Studying cell division is important because cancer often starts due to deregulation of these pathways,” says Katharine S. Ullman, PhD, a member of the Cell Response and Regulation (CRR) program at HCI and professor of oncological sciences at the University of Utah (U of U). “When we look at these steps, we begin to understand how cancer cells get around these barriers.”

Ullman and Wesley I. Sundquist, PhD, a CRR member and professor of biochemistry at the U of U, collaborated with Adam Frost, PhD, MD, at University of California at San Francisco, and Juan Martin-Serrano, PhD, a scientist and vice dean of Research and Impact at King’s College in London, on topics relating to cell division. One of the group’s projects focused on how a cell’s nucleus is formed and other changes that occur as the cell divides. The research was published in Nature in 2020.

Ullman and Sundquist mentor two trainees, Lauren Williams, PhD, and Genevieve Couldwell, who study abscission—the step of cell division that physically separates the two new cells.

Ullman and Sundquist also guide a larger collaborative team looking at abscission and its regulation.

CRR provided pilot funds that spurred on much of this cross-collaboration.

“The collaboration has been productive because we all have different backgrounds and specialties,” Ullman says. “Wesley is an expert in biochemistry and structural biology, which allows him to clarify the pathway for the abscission process. My team is focused on imaging cell division processes. Combining these different disciplinary backgrounds has been crucial to our research.”

Ullman and Sundquist now have an R01 grant from the National Institutes of Health involving multiple principal investigators. The team is working on a program project grant application.

“Understanding cell division is extremely fundamental,” Ullman states. “Yet surprisingly, there has not been a lot of attention paid to the last step of cell division, when cells disconnect, and how it is regulated. To create new tools to stop cell division, we need to know what keeps it going.”

cancer research community report melanoma cell response and regulation experimental therapeutics nuclear control of cell growth and differentiation cancer control and and population sciences

Cancer touches all of us.

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