Five teams of cancer researchers have received UF Health Cancer Center pilot funding for collaborative projects that harness the strengths of the University of Florida with The Herbert Wertheim UF Scripps Florida Institute for Biomedical Innovation and Technology.
The inaugural pilot program pairs investigators across disciplines with the goal of generating preliminary data for future cancer-focused grant applications. The program builds on the UF Health Cancer Center’s deepening collaborations with researchers at The Wertheim UF Scripps Institute. Last fall, the center expanded its research programs, creating a Cancer Targeting and Therapeutics research program that leverages leading-edge technology such as robot-assisted drug discovery to complement pharmacogenomics research at UF.
“These pilot projects will significantly accelerate the integration between cancer researchers at the Gainesville and Jupiter campuses and will lead to the development of novel therapeutic strategies supported by the National Cancer Institute in the near future,” said Rolf Renne, Ph.D., associate director for basic sciences at the UF Health Cancer Center.
Learn more about the funded pilot projects below.
Design and evaluation of RiboTACs for oncogenic long noncoding RNA targeting in lung cancer
Principal investigators: Lizi Wu, Ph.D., professor, department of molecular genetics and microbiology, UF College of Medicine and co-leader, Mechanisms of Oncogenesis research program, UF Health Cancer Center; Matthew Disney, Ph.D., professor and chair, department of chemistry, The Wertheim UF Scripps Institute
Researchers aim to develop novel compounds called ribonuclease targeting chimeras (RiboTACs) that target crucial long noncoding RNAs in lung cancer for degradation.
The research brings together the strengths of the Wu lab, which has previously identified two long noncoding RNAs crucial for tumor growth and validated them as therapeutic targets, with the Disney lab, which has pioneered a transformative technology to selectively target and degrade disease-causing RNAs.
First, the researchers will design and synthesize RiboTACs targeting specific long noncoding RNAs in lung cancer. The team will then assess their efficacy in targeted gene degradation and their impact on lung cancer in laboratory testing, with the goal of providing potential therapeutic strategies for lung cancer.
Uncovering the mechanism of oncohistone mutations in lung cancer
Principal investigators: Jonathan D. Licht, M.D., director, UF Health Cancer Center; Ciaran Seath, Ph.D., assistant professor, department of chemistry, The Wertheim UF Scripps Institute
This project will uncover how histone fold mutations alter epigenetic and signaling mechanisms that play a key role in cancer development and progression. Genomic alterations in any histone gene occur frequently in a range of cancers. Understanding how histone mutants alter molecular-level interactions between the nucleosome and proteins that regulate gene expression may provide new opportunities for therapeutic interventions.
The team will use a method called μMAP photo proximity labeling to detect proteins in the immediate microenvironment of a mutant histone. One key advantage of this method is that it causes minimal disruption to the local environment.
Initially, the team will focus on lung cancer, the deadliest cancer in the U.S., in which histone-fold mutations are expected to be found in about 10,000 patients per year.
Leveraging the Actinobacteria Strain Collection at the NPDC for anti-cancer drug discovery using screening platforms at the CNPD3
Principal investigators: Hendrik Luesch, Ph.D., professor and chair, department of medicinal chemistry and Debbie and Sylvia DeSantis Chair in Natural Products Drug Discovery and Development, UF College of Pharmacy; Ben Shen, Ph.D., professor and director, Natural Products Discovery Center, The Wertheim UF Scripps Institute
Co-investigators: Yousong Ding, Ph.D.; Yanjun Li, Ph.D.; Ranjala Ratnayake, Ph.D.
Natural products are the richest resource for anti-cancer drug discovery; more than 50% of all drugs are inspired or derived from these genetically encoded and evolutionarily optimized compounds.
This project will assess the anti-cancer potential of the Actinobacteria Strain Collection in the Natural Products Discovery Center (NPDC) library at The Wertheim UF Scripps Institute using platforms at the UF Center for Natural Products, Drug Discovery and Development (CNPD3). The team will prioritize a subset of 5,000 diverse samples for screening, with the goal of providing the basis for targeted anti-cancer studies.
The teams have complementary expertise in the exploration of natural products and the chemical and genomic level. Shen is a leader in the biosynthesis and genomics of terrestrial microbes and houses the largest actinobacteria collection in academia. Luesch is a leader in marine natural products chemistry and biology. By joining forces, the researchers will become the top team domestically in combined terrestrial and marine natural products sciences.
Development of a first-in-class small molecule therapeutic for acute myeloid leukemia
Principal investigators: Zhijian Qian, Ph.D., Pierre Chagnon Professor of Cancer Research, division of hematology and oncology, UF College of Medicine and co-leader, Mechanisms of Oncogenesis research program, UF Health Cancer Center; Courtney Miller, Ph.D., director of academic affairs and professor, The Wertheim UF Scripps Institute
Co-investigators: Jue Wang, Ph.D.; Ted Kamenecka, Ph.D.
This project aims to elucidate the role of MYH9 in acute myeloid leukemia and further delve into preliminary data suggesting its potential as a therapeutic target. The MYH9 gene, encoding the molecular motor nonmuscle myosin IIA (NMIIA), is involved in various cellular processes and overexpressed in several cancers, correlating with adverse outcomes.
In parallel, the team will continue to develop NMIIA therapeutics by identifying the optimal compound from a proprietary library of small-molecule drug leads.
The researchers will use in vitro assays, mouse genetic models and human patient models, complemented by gene expression profiling and structure-activity relationship medicinal chemistry studies. The team anticipates generating data further substantiating the therapeutic potential of NMII inhibition and identifying an NMII-based inhibitor that minimizes central nervous system effects.
Harnessing artificial intelligence for small-molecule drug discovery targeting oncogenic RNAs
Principal investigators: Yanjun Li, Ph.D., assistant professor, department of medicinal chemistry, UF College of Pharmacy; Jessica Childs-Disney, Ph.D., research assistant professor, The Wertheim UF Scripps Institute
Co-investigators: Chenglong Li, Ph.D.; Matthew Disney, Ph.D.
Genome-wide association studies have identified genes linked to cancer, yet 85% of the proteins they encode are unsuitable for drug binding. If RNA could be drugged with small molecules, it would provide a new class of targeted therapeutics. This project aims to create an innovative AI-driven computational platform to discover drug candidates from RNA-specific compound libraries.
The central hypothesis is that deep-learning algorithms can discover and define RNA-small molecule binding patterns, predict their binding affinities and identify small-molecule binders, facilitating the discovery of small-molecule drug candidates.
The long-term goal is to leverage leading-edge AI techniques to unlock the therapeutic potential of cancer-associated RNAs and establish a world-class integrated AI wet lab platform that universally identifies and refines small-molecule drugs that target them. Triple negative breast cancer is one cancer that the team’s work will target.
The UF Health Cancer Center’s pilot funding programs receive crucial support from the state of Florida through the Casey DeSantis Cancer Research Act (Fla. Stat. § 381.915).
