Valerie Horsley is an American cell and developmental biologist. She currently works as an associate professor at Yale University, where she has extensively researched the growth, restoration, and maintenance of skin cells. She is a currently a member of the Yale Cancer Center and Yale Stem Cell Center. She received a Presidential Early Career Award for Scientists and Engineers in 2012 and in 2013 she was the recipient of the Rosalind Franklin Young Investigator Award.
Early life and educationEdit
Valerie Horsley was raised by a single mother, who was working toward her doctorate in industrial engineering throughout her early childhood. Horsley was often placed in the care of graduate students, who served as her babysitters. She initially considered a career in medicine working as a physician, but opted to pursue a career in research instead. In 1998, Horsley achieved a Bachelor of Science in biology at Furman University, and later her doctorate from Emory University in 2003.
The research Horsley explored throughout the duration of her doctorate degree, which was supervised by Grace Pavlath, focused on the transcription factors involved in the development of skeletal muscle tissue. The lab that Horsley worked in discovered that smaller muscles in mice were associated with a lack of transcription factor NFATc2. She was able to determine that factor NFATc2 was a foundational component that allotted myoblast cells to fuse and develop muscle fibers. She also found that NFATc2 factor regulates the transcription of a cytokine, IL-4.
Horsley later decided to shift away from muscle research to complete her postdoctoral training under the guidance of Elaine Fuchs at Rockefeller University. It was during this process that she investigated the factors that influence stem cell development in the skin, specifically the transcription of factor Blimp-1. After finding that eliminating the gene that encoded Blimp-1 led to oily skin in mice, Horsley discovered that Blimp-1 monitors the size of the sebaceous gland.
In 2009, Horsley joined the faculty of Yale University and was promoted to an associate professor of dermatology in 2011, as well as the Maxine F. Singer ’57 Associate Professor of Molecular, Cellular and Developmental Biology.
In her Yale laboratory, Horsley has studied the cellular and molecular pathways involved in skin tissue development and maintenance, as well as the relationship between fat cells in the skin, wound healing, regeneration of hair follicles, and the formation of keratinocytes during embryonic development. Horsley currently studies adult stem cells in epithelial skin tissue and how these cells contribute to wound healing and the development of cancer, using the mouse as a genetic model system.
Through collaborations with her ex-husband Matthew Rodheffer, who is also affiliated with Yale University, Horsley has been researching the role of adipocytes, or fat cells, in hair grow. She found that within epithelial tissues, cells tend to confine to distinct micro-environments. These environments regulate cell activity with the use of adhesion between cells and various signaling molecules that were formerly unknown. Horsley and Rodheffer discovered the source of both fat cells and immune cells as local signals, as the hormone signal, prolactin, is responsible for stem cell activity and the regeneration of skin cells. Together, they also found that cell differentiation of adipocytes and hair growth occur simultaneously, and when the cell differentiation process (adipogenesis) ceases, hair growth stops and the follicles deteriorate. They identified specific adipose progenitors in the skin, which indicated the necessity of these cells to sufficiently induce hair follicle growth. These cells are activated after injury and are required for fibroblast migration during the wound healing process. Finally, they discovered that aging causes the loss of dermal adipocyte precursor cells regeneration, and therefore requires Pdgf signaling. Her research provides a link between the communication of various cells which lead to hair growth, revealing a framework for the possible regulation of hair growth and prevention of hair loss in general or in relation to various diseases.
Mechanical forces are known to regulate the development, homeostasis and regeneration of multicellular tissues. To illustrate the mechanics involved in skin function, Horlsey and Rodheffer, with E. Dufresne, used traction force microscopy to discover the physical properties of epithelial cell clusters. Using genetics, function-blocking antibodies and mathematical modeling, their work revealed the significance of physical cohesion through cadherin molecules with the coordination of mechanical force throughout multicellular clusters. Together with M. King, they identified a role of nuclear-cytoskeletal adhesion during the growth of the hair follicle. They found that inner nuclear membrane proteins of the Sun family are required for the process of keratinocyte adhesion and hair follicle structure through regulation of the cytoskeleton.
During embryonic development, a number of signal molecules as well as transcription factors are required as epidermal keratinocytes form from a single layer of ectoderm stem cells. Using mouse embryos and human embryonic skin cells, they uncovered processes that regulate the transition from ectoderm to keratinocyte. They also identified two steps that lead to keratinocyte specification, demonstrating that reduced notch signaling was essential for the first phase of keratinocyte specification.
In 2012, Horsley received the Presidential Early Career Award for Scientists and Engineers for her research of skin cell generation. Also in 2012, she was one of two recipients and received the Rosalind Franklin Young Investigator Award, presented every three years by the Genetics Society of America and the American Society of Human Genetics to two top women scientists in the field of genetics. Horsley's work and lab are supported by federal funding from the National Institutes of Health.
- "Valerie Horsley Gets Under Skin". The Scientist. Retrieved 2017-12-01.
- Stewart, Jim (March 2, 2013). "Award-winning Horsley studies skin's mysteries". Furman University. Retrieved November 14, 2015.
- "Valerie Horsley, PhD". Yale University. Retrieved November 14, 2015.
- Short, Ben (February 23, 2009). "Valerie Horsley: Getting under the skin". Journal of Cell Biology. 184 (4): 466–467. doi:10.1083/jcb.1844pi. PMC 2654133. PMID 19237594.
- Horsley, V.; et al. (2003). "IL-4 acts as a myoblast recruitment factor during mammalian muscle growth". Cell. 113 (4): 483–94. doi:10.1016/s0092-8674(03)00319-2. PMID 12757709.
- Horsley, V.; et al. (2006). "Blimp1 defines a progenitor population that governs cellular input to the sebaceous gland". Cell. 126 (3): 597–609. doi:10.1016/j.cell.2006.06.048. PMC 2424190. PMID 16901790.
- Salhotra, Pooja (September 21, 2012). "Sitting down with Valerie Horsley". The Yale Herald. Retrieved November 14, 2015.
- Peart, Karen N. (July 27, 2012). "Stem cell researcher receives top Presidential Award". YaleNews. Retrieved November 14, 2015.
- "Genes & Development -- Future Table of Contents (May 1, 2014, Volume 28, Number 9)". genesdev.cshlp.org. Retrieved 2017-12-01.
- Rivera-Gonzalez, Guillermo C.; Shook, Brett A.; Andrae, Johanna; Holtrup, Brandon; Bollag, Katherine; Betsholtz, Christer; Rodeheffer, Matthew S.; Horsley, Valerie (2016-12-01). "Skin Adipocyte Stem Cell Self-Renewal Is Regulated by a PDGFA/AKT-Signaling Axis". Cell Stem Cell. 19 (6): 738–751. doi:10.1016/j.stem.2016.09.002. ISSN 1934-5909. PMC 5135565. PMID 27746098.
- Rosowski, Kathryn A.; Mertz, Aaron F.; Norcross, Samuel; Dufresne, Eric R.; Horsley, Valerie (2015-09-22). "Edges of human embryonic stem cell colonies display distinct mechanical properties and differentiation potential". Scientific Reports. 5: 14218. doi:10.1038/srep14218. ISSN 2045-2322. PMC 4585749. PMID 26391588.
- Stewart, Rachel M.; Zubek, Amanda E.; Rosowski, Kathryn A.; Schreiner, Sarah M.; Horsley, Valerie; King, Megan C. (2015-05-11). "Nuclear–cytoskeletal linkages facilitate cross talk between the nucleus and intercellular adhesions". J Cell Biol. 209 (3): 403–418. doi:10.1083/jcb.201502024. ISSN 0021-9525. PMC 4427780. PMID 25963820.
- Tadeu, Ana Mafalda Baptista; Lin, Samantha; Hou, Lin; Chung, Lisa; Zhong, Mei; Zhao, Hongyu; Horsley, Valerie (2015-04-07). "Transcriptional Profiling of Ectoderm Specification to Keratinocyte Fate in Human Embryonic Stem Cells". PLOS ONE. 10 (4): e0122493. doi:10.1371/journal.pone.0122493. ISSN 1932-6203. PMC 4388500. PMID 25849374.
- Tadeu, Ana Mafalda Baptista; Horsley, Valerie (2013-01-01). "Notch signaling represses p63 expression in the developing surface ectoderm". Development. 140 (18): 3777–3786. doi:10.1242/dev.093948. ISSN 0950-1991. PMC 3754476. PMID 23924630.
- Pantani, Liz (August 28, 2012). "Dr. Valerie Horsley Receives the 2012 Rosalind Franklin Young Investigator Award from the Genetics Society of America". Yale School of Medicine. Retrieved November 14, 2015.