Understanding the functional role of fibroid subtype mutations for drug discovery

This project focuses on understanding the functional role of fibroid subtype mutations to accelerate drug discovery for uterine fibroids.

The fibroid subtype mutation project is positioned to leverage MSU's collaborative strengths. The project's central goal is to define how distinct somatic or subtype-specific mutations in uterine fibroids alter cellular pathways and pharmacological vulnerabilities, and to translate those mechanistic insights into actionable strategies for small-molecule or biologic discovery. A primary emphasis is on linking genotype to phenotype and then to druggable mechanisms: determining which mutated genes drive tumor growth, extracellular matrix changes, hormone responsiveness or cellular signaling in ways that expose selective targets. By characterizing mutation-specific biology, the work aims to identify biomarker-defined patient subgroups and prioritize targets that would enable precision therapeutic approaches rather than one-size-fits-all treatments.

Methodologically, the project is expected to integrate molecular characterization, functional studies and iterative medicinal chemistry and pharmacology-approaches consistent with MSU's established strengths. Molecular profiling would delineate recurrent subtype mutations and associated transcriptional or signaling alterations. Functional assays, including in vitro models and translationally relevant preclinical systems, would test the contribution of specific mutations to fibroid-relevant phenotypes and assess the effect of candidate inhibitors. The drug discovery pathway would then use these functional readouts to inform lead optimization and generate proof-of-concept data necessary for progression to animal models and potential commercialization.

This initiative seeks to translate fundamental insights about fibroid subtype mutations into targeted therapeutic approaches, improving options for patients with uterine fibroids and enabling precision strategies guided by mutation-specific biology. The work aims to produce rigorous mechanistic data and target validation that can support the next stages of drug development and clinical translation.