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Carle Illinois Student’s Research Reveals Signaling Molecule as Key to Activating Hair Regrowth

New research by a Carle Illinois College of Medicine student may unlock new naturally occurring treatments for patients with hair loss. First-year medical student Christian Guerrero-Juarez and his California-based research team is the first to identify the Scube3 molecule as the signal that can switch the body’s hair follicles from ‘dormant’ to ‘active’ mode, resulting in new hair growth. The discovery has the potential to create new therapies to treat male and female pattern hair loss.

Christian Guerrero-Juarez, Carle Illinois College of Medicine

At the base of each hair follicle is a collection of cells called the dermal papilla. Dermal papillae are composed of specialized fibroblasts that are instrumental in triggering hair follicles to grow. But in people with pattern hair loss, those cells malfunction, and fewer hair follicles become activated to reproduce and create abundant hair growth. “The genetic basis for understanding how hair follicles can be reactivated has been a mystery until now,” Guerrero-Juarez explains.

To get some answers, Guerrero-Juarez and his colleagues at the University of California-Irvine developed a model to study hair growth in mice with hyperactivated dermal papilla cells and excessive hair. “Using a combination of computational and experimental approaches, our study identified Scube3 as a new dermal papilla-specific molecule and activator of hair follicle stem cells. Our results suggest that Scube3 is a possible therapeutic treatment for androgenetic alopecia [pattern hair loss].”

Human hair folicleThis is a human scalp hair follicle stained with the following markers:
Green for KRT14 mRNA. The cyan color for KI67 mRNA. The red color for SCUBE3 mRNA. Image by Dr. Yingzi Liu.

The team took their work one step further. They microinjected Scube3 into mouse skin that had been transplanted with human scalp follicles. The injection triggered new growth in both the dormant human follicles and the surrounding host mouse follicles.

The study results were published in the journal Developmental Cell, and the University of California-Irvine has filed a provisional patent application on the use of Scube3 and its related molecular compounds for hair growth stimulation, with Guerrero-Juarez listed as a co-inventor, along with Yingzi Liu, a postdoctoral fellow and first co-author of the study, and Professor Maksim Plikus of UC-Irvine’s Department of Developmental and Cell biology and the study’s corresponding author. “We hope to continue to collaborate on this project so that we can further dissect a more detailed mechanism of how Scube3 regulates hair follicle stem cells,” Guerrero-Juarez said.

Guerrero-Juarez, who holds a Ph.D. in biological sciences, says as an incoming student at Carle Illinois College of Medicine, he hopes to pursue further research into skin stem cell biology and regeneration to help patients with skin disorders. “I’m excited to utilize my regenerative medicine and systems biology training to help tackle clinical challenges, focusing primarily on AI-inspired, next-generation tissue engineering applications. In collaboration with my fellow classmates and professors at Carle Illinois, I hope to drive innovation facilitating tissue repair and regeneration, with the goal of helping patients suffering from chronic wound-healing and scarring conditions.”

Editor’s note:

The full article “Hedgehog signaling reprograms hair follicle niche fibroblasts to a hyper-activated state,” published in Developmental Cell can be found here.

This work was supported by LEO Foundation grants LF-AW-RAM-19-400008 and LF-OC-20-000611; Chan Zuckerberg Initiative grant AN-0000000062; WM Keck Foundation grant WMKF-5634988; National Science Foundation grants DMS1951144 and DMS1763272; National Institutes of Health grants U01-AR073159, R01-AR079470, R01-AR079150, R21-AR078939 and P30-AR075047; Simons Foundation grant 594598; the National Natural Science Foundation of China; the NNSFC’s Major Research Plan training program; and Taiwan’s Ministry of Science and Technology. Guerrero-Juarez’s work was also funded by a gift from the HHMI Hanna H. Gray Postdoctoral Fellowship Program.

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