Valerie Horsley

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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.

Contents

Early life and education

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. [1] She initially considered a career in medicine working as a physician, but opted to pursue a career in research instead. [2] In 1998, Horsley achieved a Bachelor of Science in biology at Furman University, and later her doctorate from Emory University in 2003. [3]

Career

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. [4] 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. [5]

Horsley later decided to shift away from muscle research to complete her postdoctoral training under the guidance of Elaine Fuchs at Rockefeller University. [2] 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. [6]

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 Assistant Professor of Molecular, Cellular and Developmental Biology. [3]

Current research

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. [7] 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. [8]

Horsley revolutionized the field of epithelial stem cell biology by identifying skin adipocyte stem cells, establishing a major role for these progenitor cells in regulating turnover, rejuvenation and wound repair of the skin epidermis and hair follicles. [1] She found that within epithelial tissues, cells tend to confine to distinct micro-environments. Mechanisms of adipocyte cells in tissue homeostasis and regeneration are not well understood. Horsley 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. [9] Together, her laboratory 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. Her team 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. The Horsley laboratory discovered that aging causes the loss of dermal adipocyte precursor cells regeneration, and therefore requires Pdgf signaling. [10] Furthermore, adipocytes stem cells can form myofibroblasts after skin injury that generate extracellular matrix proteins and crosslink collagen and these cells are stimulated by macrophage-derived signaling proteins. [11] Her research provides a link between the communication of various cells which lead to hair growth and wound healing, revealing a framework for the possible regulation of tissue repair and the development of various diseases.

Mechanical forces are known to regulate the development, homeostasis and regeneration of multicellular tissues. To illustrate the mechanics involved in skin function, Horsley with E. Dufresne, used traction force microscopy to discover the physical properties of epithelial cell clusters. [12] 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. [13] 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. [13]

Awards

In 2008, Horsley was a regional finalist in the Blavatnik Awards for Young Scientists. [4]

In 2012, Horsley received the Presidential Early Career Award for Scientists and Engineers for her research of skin cell generation. [8] 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. [14]

In 2016, Horsley received the Montagna Lecture Award from the Society of Investigative Dermatology. [15]

In 2018, Horsley received the Graduate Division in Biomedical and Biological Sciences Distinguished Alumnus award from Emory University. [16]

Horsley's work and lab are supported by federal funding from the National Institutes of Health.

Public service

After realizing the lack of scientists in political decision making, Horsley made her first run for elected office in 2018, running for state senate in CT. [17] [18] She lost the three-way Democratic primary to Jorge Cabrera. [19]

Horsley was elected to Hamden's legislative council in CT in 2019, winning the 4th district. [20]

Controversy

In 2020, Horsley was involved in a Twitter feud. [21]

In 2021, Horsley had a dispute with fellow Hamden councilmember Justin Farmer, when she asked that he address her as "doctor", which was requested by the Hamden Council President a few months earlier in solidarity with Dr. Jill Biden. Her resignation was requested but Horsley finished her term. [22] [23]

Despite this political opposition, Horsley has actively supported diversity in science as a founding co-Chair of Society of Investigative Dermatology’s Diversity Committee. [24]

Related Research Articles

<span class="mw-page-title-main">Scar</span> Area of fibrous tissue that replaces normal skin after an injury

A scar is an area of fibrous tissue that replaces normal skin after an injury. Scars result from the biological process of wound repair in the skin, as well as in other organs, and tissues of the body. Thus, scarring is a natural part of the healing process. With the exception of very minor lesions, every wound results in some degree of scarring. An exception to this are animals with complete regeneration, which regrow tissue without scar formation.

<span class="mw-page-title-main">Keratinocyte</span> Primary type of cell found in the epidermis

Keratinocytes are the primary type of cell found in the epidermis, the outermost layer of the skin. In humans, they constitute 90% of epidermal skin cells. Basal cells in the basal layer of the skin are sometimes referred to as basal keratinocytes. Keratinocytes form a barrier against environmental damage by heat, UV radiation, water loss, pathogenic bacteria, fungi, parasites, and viruses. A number of structural proteins, enzymes, lipids, and antimicrobial peptides contribute to maintain the important barrier function of the skin. Keratinocytes differentiate from epidermal stem cells in the lower part of the epidermis and migrate towards the surface, finally becoming corneocytes and eventually being shed, which happens every 40 to 56 days in humans.

<span class="mw-page-title-main">Hair follicle</span> Organ found in the dermal layer of the mammalian skin that regulates hair growth

The hair follicle is an organ found in mammalian skin. It resides in the dermal layer of the skin and is made up of 20 different cell types, each with distinct functions. The hair follicle regulates hair growth via a complex interaction between hormones, neuropeptides, and immune cells. This complex interaction induces the hair follicle to produce different types of hair as seen on different parts of the body. For example, terminal hairs grow on the scalp and lanugo hairs are seen covering the bodies of fetuses in the uterus and in some newborn babies. The process of hair growth occurs in distinct sequential stages: anagen is the active growth phase, catagen is the regression of the hair follicle phase, telogen is the resting stage, exogen is the active shedding of hair phase and kenogen is the phase between the empty hair follicle and the growth of new hair.

<span class="mw-page-title-main">Wound healing</span> Series of events that restore integrity to damaged tissue after an injury

Wound healing refers to a living organism's replacement of destroyed or damaged tissue by newly produced tissue.

<span class="mw-page-title-main">Skin condition</span> Any medical condition that affects the integumentary system

A skin condition, also known as cutaneous condition, is any medical condition that affects the integumentary system—the organ system that encloses the body and includes skin, nails, and related muscle and glands. The major function of this system is as a barrier against the external environment.

<span class="mw-page-title-main">Regeneration (biology)</span> Biological process of renewal, restoration, and tissue growth

Regeneration in biology is the process of renewal, restoration, and tissue growth that makes genomes, cells, organisms, and ecosystems resilient to natural fluctuations or events that cause disturbance or damage. Every species is capable of regeneration, from bacteria to humans. Regeneration can either be complete where the new tissue is the same as the lost tissue, or incomplete after which the necrotic tissue becomes fibrotic.

The management of hair loss, includes prevention and treatment of alopecia, baldness, and hair thinning, and regrowth of hair.

<span class="mw-page-title-main">Elaine Fuchs</span> American cell biologist

Elaine V. Fuchs is an American cell biologist known for her work on the biology and molecular mechanisms of mammalian skin and skin diseases, who helped lead the modernization of dermatology. Fuchs pioneered reverse genetics approaches, which assess protein function first and then assess its role in development and disease. In particular, Fuchs researches skin stem cells and their production of hair and skin. She is an investigator at the Howard Hughes Medical Institute and the Rebecca C. Lancefield Professor of Mammalian Cell Biology and Development at The Rockefeller University.

<span class="mw-page-title-main">Human skin</span> Organ covering the outside of the human body

The human skin is the outer covering of the body and is the largest organ of the integumentary system. The skin has up to seven layers of ectodermal tissue guarding muscles, bones, ligaments and internal organs. Human skin is similar to most of the other mammals' skin, and it is very similar to pig skin. Though nearly all human skin is covered with hair follicles, it can appear hairless. There are two general types of skin, hairy and glabrous skin (hairless). The adjective cutaneous literally means "of the skin".

Hair multiplication or hair cloning is a proposed technique to counter hair loss. The technology to clone hair is in its early stages, but multiple groups have demonstrated pieces of the technology at a small scale with a few in commercial development.

Regeneration in humans is the regrowth of lost tissues or organs in response to injury. This is in contrast to wound healing, or partial regeneration, which involves closing up the injury site with some gradation of scar tissue. Some tissues such as skin, the vas deferens, and large organs including the liver can regrow quite readily, while others have been thought to have little or no capacity for regeneration following an injury.

<span class="mw-page-title-main">Margaret Hurlstone Hardy Fallding</span> Developmental biologist

Margaret Hurlstone Hardy Fallding was a developmental biologist in Australia and Canada who studied hair follicles.

Cédric Blanpain is a Belgian researcher in the field of stem cells. He is a tenured professor of developmental biology and genetics at Université Libre de Bruxelles and director of the stem cell and cancer lab at its Faculty of Medicine. He was one of the first researchers in the world to use cell lineage tracing in cancer research and he showed for the first time the existence of cancer stem cells in solid tumors in vivo. He was selected by Nature as one of 10 People who mattered most in 2012 and he received the outstanding young investigator award of the International Society for Stem Cell Research.

Valentina Greco is an Italian-born biologist who teaches at the Yale School of Medicine as the Carolyn Walch Slayman Professor of Genetics and is an Associate Professor in the Cell Biology and Dermatology departments. Her research focuses on the role of skin stem cells in tissue regeneration.

<span class="mw-page-title-main">Cheng-Ming Chuong</span>

Cheng-Ming Chuong is a Taiwanese-American biomedical scientist.

Angela M. Christiano is a molecular geneticist in the field of dermatology. Her research focuses on genes involved in hair and skin growth, as well as treatments for hair loss and skin cancers. She is the Richard and Mildred Rhodebeck Professor of Dermatology and Professor of Genetics and Development at Columbia University Vagelos College of Physicians and Surgeons.

<span class="mw-page-title-main">Shruti Naik</span> Indian American scientist

Shruti Naik is an Indian American scientist who is known for her interdisciplinary research in immunology and adult stem cell biology. She is an Associate Professor of Pathology, Dermatology, and Medicine and Associate Director for the Colton Center for Autoimmunity at NYU Langone Health. Her lab combines approaches from the fields of immunology, microbiology, stem cell biology, and cancer biology with cutting-edge imaging and sequencing technologies to discover new ways of treating inflammatory diseases.

CYLD cutaneous syndrome (CCS) encompasses three rare inherited cutaneous adnexal tumor syndromes: multiple familial trichoepithelioma (MFT1), Brooke–Spiegler syndrome (BSS), and familial cylindromatosis (FC). Cutaneous adnexal tumors are a large group of skin tumors that consist of tissues that have differentiated towards one of the four primary adnexal structures found in normal skin: hair follicles, sebaceous sweat glands, apocrine sweat glands, and eccrine sweat glands. CCS tumors are hair follicle tumors.

<span class="mw-page-title-main">Dermal macrophage</span> Skin macrophages used for wound repair and hair growth

Dermal macrophages are macrophages in the skin that facilitate skin homeostasis by mediating wound repair, hair growth, and salt balance. Their functional role in these processes is the mediator of inflammation. They can acquire an M1 or M2 phenotype to promote or suppress an inflammatory response, thereby influencing other cells' activity via the production of pro-inflammatory or anti-inflammatory cytokines. Dermal macrophages' ability to acquire pro-inflammatory properties also potentiates them in cancer defence. M1 macrophages can suppress tumour growth in the skin by their pro-inflammatory properties. However, M2 macrophages support tumour growth and invasion by the production of Th2 cytokines such as TGFβ and IL-10. Thus, the exact contribution of each phenotype to cancer defence and the skin's homeostasis is still unclear.

Emi K. Nishimura is a Japanese biologist who is Professor of Ageing and Regeneration at the University of Tokyo. Her research considers the molecular mechanisms that underpin ageing. She was elected Fellow of the National Academy of Sciences in 2022.

References

  1. 1 2 "Valerie Horsley Gets Under Skin". The Scientist. Retrieved 2017-12-01.
  2. 1 2 Stewart, Jim (March 2, 2013). "Award-winning Horsley studies skin's mysteries". Furman University. Archived from the original on November 17, 2015. Retrieved November 14, 2015.
  3. 1 2 "Valerie Horsley, PhD". Yale University . Retrieved November 14, 2015.
  4. 1 2 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.
  5. ↑ 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. S2CID   2111982.
  6. ↑ 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.
  7. ↑ Salhotra, Pooja (September 21, 2012). "Sitting down with Valerie Horsley". The Yale Herald . Retrieved November 14, 2015.
  8. 1 2 Peart, Karen N. (July 27, 2012). "Stem cell researcher receives top Presidential Award". YaleNews. Retrieved November 14, 2015.
  9. ↑ "Genes & Development – Future Table of Contents (May 1, 2014, Volume 28, Number 9)". genesdev.cshlp.org. Retrieved 2017-12-01.
  10. ↑ 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.
  11. ↑ Horsley, Valerie; Hsia, Henry C.; Clark, Damon A.; Miller-Jensen, Kathryn; Arbiser, Jack L.; Lei, Vivian; Zwick, Rachel K.; Aultman, Krystal D.; Muñoz-Rojas, Andrés R. (2018-11-23). "Myofibroblast proliferation and heterogeneity are supported by macrophages during skin repair". Science. 362 (6417): eaar2971. Bibcode:2018Sci...362R2971S. doi:10.1126/science.aar2971. ISSN   0036-8075. PMC   6684198 . PMID   30467144.
  12. ↑ 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. Bibcode:2015NatSR...514218R. doi:10.1038/srep14218. ISSN   2045-2322. PMC   4585749 . PMID   26391588.
  13. 1 2 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.
  14. ↑ 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.
  15. ↑ "Valerie Horsley, PhD, presenting at IID 2018". IID 2018. Archived from the original on 2019-06-07. Retrieved 2019-06-06.
  16. ↑ "Valerie Horsley receives Emory University's Graduate Division of Biological and Biomedical Sciences Distinguished Alumnus Award. | Molecular, Cellular and Developmental Biology". mcdb.yale.edu. Retrieved 2019-06-06.
  17. ↑ Altimari, Daniela (20 February 2018). "Yale Scientist Plans Run for State Senate". courant.com. Retrieved 2020-06-19.
  18. ↑ "Truth-seeking scientists run for office". BBC News. Retrieved 2020-06-19.
  19. ↑ Lambert, Ben (2018-08-15). "Cabrera wins Democratic race in 17th District, will face Logan in November". New Haven Register. Retrieved 2020-06-19.
  20. ↑ "The Times In Hamden: Are They A-Changin'? | New Haven Independent". www.newhavenindependent.org. 2019-11-06. Retrieved 2020-06-19.
  21. ↑ Jones, Asher Elbein,Tyler O. (August 2, 2020). "Worm Joke Causes Science Twitter Flame War Over Accusations of Sexism and Racism". The Daily Beast– via www.thedailybeast.com.{{cite news}}: CS1 maint: multiple names: authors list (link)
  22. ↑ "Activists call for Hamden councilwoman to resign over public comments| New Haven Register". www.nhregister.org. 2021-04-12. Retrieved 2021-04-16.
  23. ↑ "Activists demand Yale professor Valerie Horsley resign from Hamden Legislative Council| Yale Daily News". yaledailynews.com. 2021-04-16. Retrieved 2021-04-16.
  24. ↑ Horsley, Valerie; Glass, Donald; Minnillo, Rebecca; Gallo, Richard; Cruz, Ponciano; Ward, Nicole L. (October 2019). "Diversity is Excellence: Initiatives in the Society for Investigative Dermatology to Broaden Participation". The Journal of Investigative Dermatology. 139 (10): 2217–2219. doi: 10.1016/j.jid.2019.07.695 . ISSN   1523-1747. PMID   31381893. S2CID   199449092.
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