Valerie Horsley, PhD
Associate Professor of Molecular, Cellular, and Developmental Biology and Associate Professor of Dermatology
Research & Publications
Biography
News
Research Summary
Our laboratory studies the cellular and molecular mechanisms that control stem cell activity and function within epithelia, the tissues that line our internal organs and outer surfaces. We use the mouse as a genetic model system to study how adult stem cells within epithelial tissues maintain tissue homeostasis, wound healing and can contribute to cancer formation. The primary epithelial tissue we use is the mammalian skin, which contains multiple stem cell populations and forms a complex tissue that protects our bodies from external pathogens and loss of internal bodily fluids. Mammalian skin is an excellent model to study developmental and stem cell biology because the epidermis and its appendages are in a constant state of regeneration, which is actively sustained by tissue stem cells.
Our vision is to understand the cellular and molecular regulation of epithelial tissue development and regeneration. We focus on both the intrinsic transcriptional as well as the extrinsic signaling mechanisms that control these processes.
Coauthors
Research Interests
Dermatology; Epithelial Cells; Molecular Biology; Regeneration; Skin Diseases; Stem Cells; Tissue Survival
Research Image
Skin highlighting dermal adipocytes
Adiponectin-Cre; mT/mG mice show adipocytes with mG+ membranes surrounding mature hair follicles in the skin
Selected Publications
- NFATc1 balances quiescence and proliferation of skin stem cells.Horsley V, Aliprantis AO, Polak L, Glimcher LH, Fuchs E. NFATc1 balances quiescence and proliferation of skin stem cells. Cell 2008, 132:299-310.
- Blimp1 defines a progenitor population that governs cellular input to the sebaceous gland.Horsley V, O'Carroll D, Tooze R, Ohinata Y, Saitou M, Obukhanych T, Nussenzweig M, Tarakhovsky A, Fuchs E. Blimp1 defines a progenitor population that governs cellular input to the sebaceous gland. Cell 2006, 126:597-609.
- Adipocyte lineage cells contribute to the skin stem cell niche to drive hair cycling.Festa E, Fretz J, Berry R, Schmidt B, Rodeheffer M, Horowitz M, Horsley V. Adipocyte lineage cells contribute to the skin stem cell niche to drive hair cycling. Cell 2011, 146:761-71.
- Intradermal adipocytes mediate fibroblast recruitment during skin wound healing.Schmidt BA, Horsley V. Intradermal adipocytes mediate fibroblast recruitment during skin wound healing. Development (Cambridge, England) 2013, 140:1517-27.
- Transcriptional profiling of ectoderm specification to keratinocyte fate in human embryonic stem cells.Tadeu AM, Lin S, Hou L, Chung L, Zhong M, Zhao H, Horsley V. Transcriptional profiling of ectoderm specification to keratinocyte fate in human embryonic stem cells. PloS One 2015, 10:e0122493.
- Edges of human embryonic stem cell colonies display distinct mechanical properties and differentiation potential.Rosowski KA, Mertz AF, Norcross S, Dufresne ER, Horsley V. Edges of human embryonic stem cell colonies display distinct mechanical properties and differentiation potential. Scientific Reports 2015, 5:14218.
- Nuclear-cytoskeletal linkages facilitate cross talk between the nucleus and intercellular adhesions.Stewart RM, Zubek AE, Rosowski KA, Schreiner SM, Horsley V, King MC. Nuclear-cytoskeletal linkages facilitate cross talk between the nucleus and intercellular adhesions. The Journal Of Cell Biology 2015, 209:403-18.
- Loss of endogenous Nfatc1 reduces the rate of DMBA/TPA-induced skin tumorigenesis.Goldstein J, Roth E, Roberts N, Zwick R, Lin S, Fletcher S, Tadeu A, Wu C, Beck A, Zeiss C, Suárez-Fariñas M, Horsley V. Loss of endogenous Nfatc1 reduces the rate of DMBA/TPA-induced skin tumorigenesis. Molecular Biology Of The Cell 2015, 26:3606-14.
- Skin Adipocyte Stem Cell Self-Renewal Is Regulated by a PDGFA/AKT-Signaling Axis.Rivera-Gonzalez GC, Shook BA, Andrae J, Holtrup B, Bollag K, Betsholtz C, Rodeheffer MS, Horsley V. Skin Adipocyte Stem Cell Self-Renewal Is Regulated by a PDGFA/AKT-Signaling Axis. Cell Stem Cell 2016, 19:738-751.
- NFAT: ubiquitous regulator of cell differentiation and adaptation.Horsley V, Pavlath GK. NFAT: ubiquitous regulator of cell differentiation and adaptation. The Journal Of Cell Biology 2002, 156:771-4.
- Cell fusion in skeletal muscle--central role of NFATC2 in regulating muscle cell size.Pavlath GK, Horsley V. Cell fusion in skeletal muscle--central role of NFATC2 in regulating muscle cell size. Cell Cycle (Georgetown, Tex.) 2003, 2:420-3.
- Prostaglandin F2(alpha) stimulates growth of skeletal muscle cells via an NFATC2-dependent pathway.Horsley V, Pavlath GK. Prostaglandin F2(alpha) stimulates growth of skeletal muscle cells via an NFATC2-dependent pathway. The Journal Of Cell Biology 2003, 161:111-8.
- IL-4 acts as a myoblast recruitment factor during mammalian muscle growth.Horsley V, Jansen KM, Mills ST, Pavlath GK. IL-4 acts as a myoblast recruitment factor during mammalian muscle growth. Cell 2003, 113:483-94.
- Forming a multinucleated cell: molecules that regulate myoblast fusion.Horsley V, Pavlath GK. Forming a multinucleated cell: molecules that regulate myoblast fusion. Cells, Tissues, Organs 2004, 176:67-78.
- Epithelial stem cells: turning over new leaves.Blanpain C, Horsley V, Fuchs E. Epithelial stem cells: turning over new leaves. Cell 2007, 128:445-58.
- Reprogramming somatic cells to their embryonic state.Horsley V, Fuchs E. Reprogramming somatic cells to their embryonic state. HFSP Journal 2007, 1:89-93.
- More than one way to skin . . .Fuchs E, Horsley V. More than one way to skin . . . Genes & Development 2008, 22:976-85.
- FOXC2 controls formation and maturation of lymphatic collecting vessels through cooperation with NFATc1.Norrmén C, Ivanov KI, Cheng J, Zangger N, Delorenzi M, Jaquet M, Miura N, Puolakkainen P, Horsley V, Hu J, Augustin HG, Ylä-Herttuala S, Alitalo K, Petrova TV. FOXC2 controls formation and maturation of lymphatic collecting vessels through cooperation with NFATc1. The Journal Of Cell Biology 2009, 185:439-57.
- Epigenetics, Wnt signaling, and stem cells: the Pygo2 connection.Horsley V. Epigenetics, Wnt signaling, and stem cells: the Pygo2 connection. The Journal Of Cell Biology 2009, 185:761-3.
- Valerie Horsley: getting under the skin. Interview by Ben Short.Horsley V. Valerie Horsley: getting under the skin. Interview by Ben Short. The Journal Of Cell Biology 2009, 184:466-7.
- Ferreting out stem cells from their niches.Fuchs E, Horsley V. Ferreting out stem cells from their niches. Nature Cell Biology 2011, 13:513-8.
- Upward bound: follicular stem cell fate decisions.Horsley V. Upward bound: follicular stem cell fate decisions. The EMBO Journal 2011, 30:2986-7.
- Development and homeostasis of the sebaceous gland.Niemann C, Horsley V. Development and homeostasis of the sebaceous gland. Seminars In Cell & Developmental Biology 2012, 23:928-36.
- Unravelling hair follicle-adipocyte communication.Schmidt B, Horsley V. Unravelling hair follicle-adipocyte communication. Experimental Dermatology 2012, 21:827-30.
- Scaling of traction forces with the size of cohesive cell colonies.Mertz AF, Banerjee S, Che Y, German GK, Xu Y, Hyland C, Marchetti MC, Horsley V, Dufresne ER. Scaling of traction forces with the size of cohesive cell colonies. Physical Review Letters 2012, 108:198101.
- Split decisions: oesophageal progenitor cell behaviour.Horsley V. Split decisions: oesophageal progenitor cell behaviour. The EMBO Journal 2012, 31:3653-4.
- Home sweet home: skin stem cell niches.Goldstein J, Horsley V. Home sweet home: skin stem cell niches. Cellular And Molecular Life Sciences : CMLS 2012, 69:2573-82.
- Notch signaling represses p63 expression in the developing surface ectoderm.Tadeu AM, Horsley V. Notch signaling represses p63 expression in the developing surface ectoderm. Development (Cambridge, England) 2013, 140:3777-86.
- Cadherin-based intercellular adhesions organize epithelial cell-matrix traction forces.Mertz AF, Che Y, Banerjee S, Goldstein JM, Rosowski KA, Revilla SF, Niessen CM, Marchetti MC, Dufresne ER, Horsley V. Cadherin-based intercellular adhesions organize epithelial cell-matrix traction forces. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110:842-7.
- IL-22 promotes fibroblast-mediated wound repair in the skin.McGee HM, Schmidt BA, Booth CJ, Yancopoulos GD, Valenzuela DM, Murphy AJ, Stevens S, Flavell RA, Horsley V. IL-22 promotes fibroblast-mediated wound repair in the skin. The Journal Of Investigative Dermatology 2013, 133:1321-9.
- Characterization of Cre recombinase models for the study of adipose tissue.Jeffery E, Berry R, Church CD, Yu S, Shook BA, Horsley V, Rosen ED, Rodeheffer MS. Characterization of Cre recombinase models for the study of adipose tissue. Adipocyte 2014, 3:206-11.
- Developing stratified epithelia: lessons from the epidermis and thymus.Roberts N, Horsley V. Developing stratified epithelia: lessons from the epidermis and thymus. Wiley Interdisciplinary Reviews. Developmental Biology 2014, 3:389-402.
- Defining dermal adipose tissue.Driskell RR, Jahoda CA, Chuong CM, Watt FM, Horsley V. Defining dermal adipose tissue. Experimental Dermatology 2014, 23:629-31.
- Adipocytes in skin health and disease.Rivera-Gonzalez G, Shook B, Horsley V. Adipocytes in skin health and disease. Cold Spring Harbor Perspectives In Medicine 2014, 4.
- Epithelial stem cells in adult skin.Tadeu AM, Horsley V. Epithelial stem cells in adult skin. Current Topics In Developmental Biology 2014, 107:109-31.
- Pygo2 regulates β-catenin-induced activation of hair follicle stem/progenitor cells and skin hyperplasia.Sun P, Watanabe K, Fallahi M, Lee B, Afetian ME, Rheaume C, Wu D, Horsley V, Dai X. Pygo2 regulates β-catenin-induced activation of hair follicle stem/progenitor cells and skin hyperplasia. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111:10215-20.
- Calcineurin/Nfatc1 signaling links skin stem cell quiescence to hormonal signaling during pregnancy and lactation.Goldstein J, Fletcher S, Roth E, Wu C, Chun A, Horsley V. Calcineurin/Nfatc1 signaling links skin stem cell quiescence to hormonal signaling during pregnancy and lactation. Genes & Development 2014, 28:983-94.
- Dermal white adipose tissue: a new component of the thermogenic response.Alexander CM, Kasza I, Yen CL, Reeder SB, Hernando D, Gallo RL, Jahoda CA, Horsley V, MacDougald OA. Dermal white adipose tissue: a new component of the thermogenic response. Journal Of Lipid Research 2015, 56:2061-9.
- Origin of fibrosing cells in systemic sclerosis.Ebmeier S, Horsley V. Origin of fibrosing cells in systemic sclerosis. Current Opinion In Rheumatology 2015, 27:555-62.
- Montagna Symposium 2015: Harnessing Stem Cells to Reveal Novel Skin Biology and Disease Treatments.Horsley V, Kulesz-Martin M, Wang XJ. Montagna Symposium 2015: Harnessing Stem Cells to Reveal Novel Skin Biology and Disease Treatments. The Journal Of Investigative Dermatology 2016, 136:893-896.
- The Role of Adipocytes in Tissue Regeneration and Stem Cell Niches.Shook B, Rivera Gonzalez G, Ebmeier S, Grisotti G, Zwick R, Horsley V. The Role of Adipocytes in Tissue Regeneration and Stem Cell Niches. Annual Review Of Cell And Developmental Biology 2016, 32:609-631.
- Pigment epithelium-derived factor restoration increases bone mass and improves bone plasticity in a model of osteogenesis imperfecta type VI via Wnt3a blockade.Belinsky GS, Sreekumar B, Andrejecsk JW, Saltzman WM, Gong J, Herzog RI, Lin S, Horsley V, Carpenter TO, Chung C. Pigment epithelium-derived factor restoration increases bone mass and improves bone plasticity in a model of osteogenesis imperfecta type VI via Wnt3a blockade. FASEB Journal : Official Publication Of The Federation Of American Societies For Experimental Biology 2016, 30:2837-48.
- CD301b+ Macrophages Are Essential for Effective Skin Wound Healing.Shook B, Xiao E, Kumamoto Y, Iwasaki A, Horsley V. CD301b+ Macrophages Are Essential for Effective Skin Wound Healing. The Journal Of Investigative Dermatology 2016, 136:1885-1891.
- Prdm1 Regulates Thymic Epithelial Function To Prevent Autoimmunity.Roberts NA, Adams BD, McCarthy NI, Tooze RM, Parnell SM, Anderson G, Kaech SM, Horsley V. Prdm1 Regulates Thymic Epithelial Function To Prevent Autoimmunity. Journal Of Immunology (Baltimore, Md. : 1950) 2017, 199:1250-1260.
- Repeal and Replace: Adipocyte Regeneration in Wound Repair.Horsley V, Watt F. Repeal and Replace: Adipocyte Regeneration in Wound Repair. Cell Stem Cell 2017, 20:424-426.
- Tregs Expand the Skin Stem Cell Niche.Horsley V, Naik S. Tregs Expand the Skin Stem Cell Niche. Developmental Cell 2017, 41:455-456.
- E-cadherin integrates mechanotransduction and EGFR signaling to control junctional tissue polarization and tight junction positioning.Rübsam M, Mertz AF, Kubo A, Marg S, Jüngst C, Goranci-Buzhala G, Schauss AC, Horsley V, Dufresne ER, Moser M, Ziegler W, Amagai M, Wickström SA, Niessen CM. E-cadherin integrates mechanotransduction and EGFR signaling to control junctional tissue polarization and tight junction positioning. Nature Communications 2017, 8:1250.
- PDGFA regulation of dermal adipocyte stem cells.Rivera-Gonzalez GC, Shook BA, Horsley V. PDGFA regulation of dermal adipocyte stem cells. Stem Cell Investigation 2017, 4:72.
- Anatomical, Physiological, and Functional Diversity of Adipose Tissue.Zwick RK, Guerrero-Juarez CF, Horsley V, Plikus MV. Anatomical, Physiological, and Functional Diversity of Adipose Tissue. Cell Metabolism 2018, 27:68-83.
- Adipocyte hypertrophy and lipid dynamics underlie mammary gland remodeling after lactation.Zwick RK, Rudolph MC, Shook BA, Holtrup B, Roth E, Lei V, Van Keymeulen A, Seewaldt V, Kwei S, Wysolmerski J, Rodeheffer MS, Horsley V. Adipocyte hypertrophy and lipid dynamics underlie mammary gland remodeling after lactation. Nature Communications 2018, 9:3592.
- Myofibroblast proliferation and heterogeneity are supported by macrophages during skin repair.Shook BA, Wasko RR, Rivera-Gonzalez GC, Salazar-Gatzimas E, López-Giráldez F, Dash BC, Muñoz-Rojas AR, Aultman KD, Zwick RK, Lei V, Arbiser JL, Miller-Jensen K, Clark DA, Hsia HC, Horsley V. Myofibroblast proliferation and heterogeneity are supported by macrophages during skin repair. Science (New York, N.Y.) 2018, 362.
- Thin Skinned: Aged Adipocyte Atrophy Impacts Innate Immunity.Wasko RR, Horsley V. Thin Skinned: Aged Adipocyte Atrophy Impacts Innate Immunity. Trends In Immunology 2019, 40:175-177.
- Diversity is Excellence: Initiatives in the Society for Investigative Dermatology to Broaden Participation.Horsley V, Glass D, Minnillo R, Gallo R, Cruz P, Ward N. Diversity is Excellence: Initiatives in the Society for Investigative Dermatology to Broaden Participation. The Journal Of Investigative Dermatology 2019, 139:2217-2219.
- Calcineurin activity is required for the initiation of skeletal muscle differentiation.Friday BB, Horsley V, Pavlath GK. Calcineurin activity is required for the initiation of skeletal muscle differentiation. The Journal Of Cell Biology 2000, 149:657-66.
- Regulation of the growth of multinucleated muscle cells by an NFATC2-dependent pathway.Horsley V, Friday BB, Matteson S, Kegley KM, Gephart J, Pavlath GK. Regulation of the growth of multinucleated muscle cells by an NFATC2-dependent pathway. The Journal Of Cell Biology 2001, 153:329-38.
- Lifting Each Other Up: Epidermal Stem Cells in Tissue Homeostasis.Horsley V. Lifting Each Other Up: Epidermal Stem Cells in Tissue Homeostasis. Developmental Cell 2019, 51:296-298.
- Regulated in Development and DNA Damage Responses 1 Prevents Dermal Adipocyte Differentiation and Is Required for Hair Cycle-Dependent Dermal Adipose Expansion.Rivera-Gonzalez GC, Klopot A, Sabin K, Baida G, Horsley V, Budunova I. Regulated in Development and DNA Damage Responses 1 Prevents Dermal Adipocyte Differentiation and Is Required for Hair Cycle-Dependent Dermal Adipose Expansion. The Journal Of Investigative Dermatology 2020, 140:1698-1705.e1.
- Small-scale demixing in confluent biological tissues.Sahu P, Sussman DM, Rübsam M, Mertz AF, Horsley V, Dufresne ER, Niessen CM, Marchetti MC, Manning ML, Schwarz JM. Small-scale demixing in confluent biological tissues. Soft Matter 2020, 16:3325-3337.
- Skin in the Game: Stem Cells in Repair, Cancer, and Homeostasis.Horsley V. Skin in the Game: Stem Cells in Repair, Cancer, and Homeostasis. Cell 2020, 181:492-494.
- Dermal Adipocyte Lipolysis and Myofibroblast Conversion Are Required for Efficient Skin Repair.Shook BA, Wasko RR, Mano O, Rutenberg-Schoenberg M, Rudolph MC, Zirak B, Rivera-Gonzalez GC, López-Giráldez F, Zarini S, Rezza A, Clark DA, Rendl M, Rosenblum MD, Gerstein MB, Horsley V. Dermal Adipocyte Lipolysis and Myofibroblast Conversion Are Required for Efficient Skin Repair. Cell Stem Cell 2020, 26:880-895.e6.
- Statement on Racial Equality.Glass D, Gonzalez GR, Horsley V, Linos E. Statement on Racial Equality. The Journal Of Investigative Dermatology 2020, 140:1485.
- The LINC complex transmits integrin-dependent tension to the nuclear lamina and represses epidermal differentiation.Carley E, Stewart R, Zieman AG, Jalilian I, King DE, Zubek AE, Lin S, Horsley V, King MC. The LINC complex transmits integrin-dependent tension to the nuclear lamina and represses epidermal differentiation. ELife 2021, 10.
- Fibroblasts: Origins, definitions, and functions in health and disease.Plikus MV, Wang X, Sinha S, Forte E, Thompson SM, Herzog EL, Driskell RR, Rosenthal N, Biernaskie J, Horsley V. Fibroblasts: Origins, definitions, and functions in health and disease. Cell 2021, 184:3852-3872.