Miller School Researchers Receive State Funding for Drug-Discovery Projects

Miller School of Medicine researchers have received three grants in the latest round of funding from the Florida Translational Research Program (FTRP), a state-funded initiative to advance drug discovery. All of the projects receiving awards focus on the discovery and development of novel small molecules for the treatment of disease, specifically cancer. This brings the total number of grants awarded to Miller School researchers in the two-year-old FTRP to six.

The primary investigators in the three newly funded projects are Claes Wahlestedt, M.D., Ph.D., Leonard M. Miller Professor, Associate Dean for Therapeutic Innovation, Vice Chair for Research in the Department of Psychiatry and Behavioral Sciences, and Director of the Center for Therapeutic Innovation; Joseph Rosenblatt, M.D., professor of medicine, microbiology and immunology, Chief of the Division of Hematology and Oncology in the Department of Medicine, and William J. Harrington Chair in Hematology; and Glen Barber, Ph.D., professor and Chair of the Department of Cell Biology, and Associate Director of Basic Science at the Sylvester Comprehensive Cancer Center.

The FTRP is funded through the Florida Department of Health and administered by the Sanford-Burnham Medical Research Institute at Lake Nona, which provides high-throughput screening for the research projects. The Miller School participates primarily through its Center for Therapeutic Innovation, which is focused on the discovery and development of novel therapeutics, as well as the evaluation of clinically approved compounds for efficacy in treating disease. The goal of the Center for Therapeutic Innovation is to create a pipeline to support the development of novel research programs by University of Miami scientists.

Wahlestedt has been the recipient of three of the six FTRP awards. His most recent award will fund a study of the histone-modifying epigenetic enzyme PRMT5, which causes cancer cells to grow. The research involves high-throughput screening of tens of thousands of compounds to look for those that inhibit this enzyme, which has been the focus of years of research performed in the laboratory of Stephen D. Nimer, M.D., professor of medicine, biochemistry and molecular biology, and Director of the Sylvester Comprehensive Cancer Center, and led by Fan Liu, Ph.D., research assistant professor of biochemistry and molecular biology. Wahlestedt’s prior two awards supported similar studies of a different epigenetic enzyme, MLL3, which has also been strongly implicated in cancer growth.

“A key to our success is that we are not only experts in drug discovery here at the Miller School, but that we also collaborate very closely with experts, such as Dr. Nimer, on the diseases and the drug targets that we are pursuing,” said Wahlestedt.

Rosenblatt was awarded an assay development grant to inhibit vasculogenic mimicry, which refers to the ability of tumors to directly form their own blood supply through the formation of channels by tumor cells, as well as the mobilization of endothelial cells. He is conducting the study with co-principal investigator Seung-Uon Shin, Ph.D., research associate professor of medicine in the Division of Hematology and Oncology.

“When you put tumor cells and endothelial cells together, they appear to have a way of communicating and working together to build a capillary network — almost like a scaffolding — to feed the tumor,” said Rosenblatt. “We will be screening for agents that disrupt that activity.”

Barber was awarded a grant for continuing research into how the immune system rallies to fight DNA pathogens, such as cancer-causing viruses. His laboratory has discovered a molecule called STING (Stimulators of Interferon Genes), which has been shown to be essential for controlling immune system responses. Activation of STING by DNA pathogens or DNA damage triggers the production of cytokines that invoke anti-microbial activity and anti-cancer activity through stimulation of the adaptive immune response.

“Isolating activators of STING will lead to the generation of new adjuvants for use in novel vaccine or cancer immunotherapeutic strategies,” said Barber. “Conversely, discovering compounds that suppress STING activity may lead to new treatments for inflammatory-related disease, including cancer.”

The other prior FTRP grant recipient from the Miller School was Shaun Brothers, Ph.D., assistant professor of psychiatry and behavioral sciences, and one of the founding members of the Center for Therapeutic Innovation. He received an award to find small molecules for HIF2alpha, a protein that is expressed when cancer cells adapt to hypoxia, which many cells must do in order to thrive. This work is being performed in collaboration with Stephen Lee, Ph.D., professor of biochemistry and molecular biology, who discovered the importance of inhibiting HIF2alpha in cancer.

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