Telocyte-targeted small molecule modulators to switch hair follicle growth on and off

This project develops small molecules that modulate telocytes-specialized stromal cells to secrete Wnt or BMP ligands to switch human hair follicles into growth or arrest modes on demand. It targets the niche rather than the follicle itself, opening a new control point for hair biology in both medical and aesthetic settings.

The screening array will use a medium-throughput 384-well plate platform combining telocyte-conditioned media with reporter cell lines for Wnt or BMP pathway activity (b-catenin- and phosphorylated SMAD1/5/8-responsive reporters). The initial library will include approximately 1,000 small molecules enriched for Wnt/BMP modulators and secretory‑pathway regulators, each tested across 6-8 concentrations. Key metrics will be quantitative reporter activity together with multiplexed measurements of telocyte-secreted factors (for example Wnts, BMPs, and cytokines) in conditioned media. Automated imaging and dose-response modeling will be used to calculate EC50/IC50 values and prioritize hits for follow‑up.

Secretome profiling will quantify how candidate compounds reprogram telocyte outputs and how these changes translate into hair follicle behavior in human skin explants. Key metrics will include multiplexed measurements of Wnts, BMPs, and inflammatory cytokines in telocyte‑conditioned media, analyzed as both absolute concentrations and pathway-level “signatures” associated with pro‑growth or growth‑arrest states. In parallel, top hits will be tested in human explants, measuring time to anagen entry, hair shaft elongation over 3–10 days, and the fraction of follicles entering growth versus remaining quiescent. By linking specific secretome shifts (for example, increased Wnt/low BMP or the converse) with quantifiable changes in hair shaft length and follicle-cycle state in explants, we can define mechanism-anchored pharmacodynamic markers and prioritize compounds with the strongest, most predictable control of hair growth.