# Valerie Horsley: Getting under the Skin

Post on 30-Jan-2017

218 views

Category:

## Documents

<ul><li><p>Valerie Horsley: Getting under the SkinAuthor(s): Valerie Horsley and Ben ShortSource: The Journal of Cell Biology, Vol. 184, No. 4 (Feb. 23, 2009), pp. 466-467Published by: The Rockefeller University PressStable URL: http://www.jstor.org/stable/20537165 .Accessed: 24/06/2014 21:42</p><p>Your use of the JSTOR archive indicates your acceptance of the Terms &amp; Conditions of Use, available at .http://www.jstor.org/page/info/about/policies/terms.jsp</p><p> .JSTOR is a not-for-profit service that helps scholars, researchers, and students discover, use, and build upon a wide range ofcontent in a trusted digital archive. We use information technology and tools to increase productivity and facilitate new formsof scholarship. For more information about JSTOR, please contact support@jstor.org.</p><p> .</p><p>The Rockefeller University Press is collaborating with JSTOR to digitize, preserve and extend access to TheJournal of Cell Biology.</p><p>http://www.jstor.org </p><p>This content downloaded from 185.2.32.106 on Tue, 24 Jun 2014 21:42:22 PMAll use subject to JSTOR Terms and Conditions</p><p>http://www.jstor.org/action/showPublisher?publisherCode=rupresshttp://www.jstor.org/stable/20537165?origin=JSTOR-pdfhttp://www.jstor.org/page/info/about/policies/terms.jsphttp://www.jstor.org/page/info/about/policies/terms.jsp</p></li><li><p>People &amp; Ideas </p><p>Valerie Horsley: Getting under the skin Valerie Horsley investigates the regulation and differentiation of stem cells </p><p>in mammalian skin. </p><p>Epidermal stem cells in mammalian </p><p>skin can develop primarily along three alternative paths, differenti </p><p>ating into hair follicles, sebaceous glands, or the interfollicular epidermis. How the stem cells are guided into these different fates by signaling molecules and tran </p><p>scription factors is a question that first </p><p>grabbed Valerie Horsley's interest as a </p><p>postdoc in Elaine Fuchs' laboratory at the </p><p>Rockefeller University. Now an assistant </p><p>professor at Yale University, she's continu </p><p>ing to use a powerful combination of </p><p>mouse genetics and cell biology to study how the skin is developed and maintained. </p><p>Before her time at Rockefeller, Horsley attended Furman University as an under </p><p>graduate, and studied for her PhD with Grace Pavlath at Emory </p><p>"When I got to Emory, </p><p>I didn't know what research </p><p>was really like. My first </p><p>year there was a great </p><p>learning experience/7 </p><p>University in Atlanta. In Pavlath's laboratory, she </p><p>worked on signaling path </p><p>ways and transcription factors regulating skeletal </p><p>muscle development ( 1-3). </p><p>As a postdoc, she switched </p><p>her attention to skin, look </p><p>ing at the functions of two </p><p>transcription factors in </p><p>particular: NFATc 1, which controls the exit of epider mal stem cells from their </p><p>niche to grow new hair </p><p>follicles (4), and Blimp 1, which regulates the differentiation of spe cific precursor cells into the sebaceous </p><p>gland (5). We caught up with Horsley to ask her </p><p>about these precursor stages of her career </p><p>and her recent differentiation into an inde </p><p>pendent group leader at Yale. </p><p>AN EARLY START What do you think you'd be if you weren't a scientist? </p><p>I kind of always knew I was going to be a scientist. I wanted to be a doctor when I </p><p>was a kid, but that's because it was the only </p><p>thing I knew you could do as a career that's </p><p>science-y. When I was in college, I realized </p><p>that I didn't really want to take care of sick </p><p>people. I was more interested in how the </p><p>body works?that's why research really </p><p>suited me better than medicine. </p><p>What gave you this idea at such a </p><p>young age? I think it's mostly just my personality. But when I was 12, I had a biology teacher who told stories and made it really inter </p><p>esting. We did experiments, and it was a </p><p>lot of fun. That really inspired me. From then on, I knew I wanted to be a scientist. </p><p>What kind of experiments did you do? We put plants in black boxes with differ ent colored light and tried to see which ones they could grow in. That's the only one I remember. When I was in ninth </p><p>grade I went to the Fernbank Science Center in Atlanta, which has a science </p><p>program. High school students attend </p><p>one- or two-week classes in physics, </p><p>ornithology?all these different science </p><p>classes over the course of three months. We </p><p>did a few experiments there. I thought clon </p><p>ing was cool after going to this program, so </p><p>I remember trying to clone plants for a sci </p><p>ence fair project! When you're a kid, you </p><p>need to come up with ideas for doing ex </p><p>periments and I think our education system </p><p>could be better at stimulating those ideas. </p><p>When did you get your first proper taste </p><p>of being in a laboratory? When I went to grad school, really. Furman </p><p>is a very small undergraduate college, so there's not a large research enterprise. </p><p>When I got to Emory, I didn't know what research was really like. My first </p><p>year there was a great learning experi </p><p>ence, I learned a ton. </p><p>TRANSCRIPTION AND TISSUES What made you choose Grace Pavlathfs </p><p>laboratory? I'm interested in how the body works and she was one of the only faculty members </p><p>Valerie Horsley with her daughter, Avery. </p><p>at Emory who was really working on tis </p><p>sue function. She had a lot of interesting cell and developmental biology projects in the laboratory, working on skeletal </p><p>muscle. I looked at how NFATc2, which is a transcription factor, controls muscle </p><p>development. I identified an intermediate </p><p>stage of muscle development, in which </p><p>multinucleated myotubes grow larger </p><p>by recruiting additional nuclei. NFATc2 controls that step. </p><p>I found that a secreted factor, IL-4, is </p><p>released from these initial myotubes and </p><p>gives that "come fuse with me" signal. I </p><p>also did some work on prostaglandins and </p><p>how they control this stage of myogenesis as well. That was my first love: I still love that project! </p><p>So why did you change fields for your postdoc? A few of my favorite faculty at Emory told </p><p>me, "Don't change, stay in muscle devel </p><p>opment," but I really thought it would broaden me to go to a different tissue. Bone </p><p>development was initially what I wanted to </p><p>do, but I also wanted to go to a large </p><p>laboratory and work with someone that was </p><p>famous. Skin development seemed like it had a lot of tools to study developmental questions, so I came to Rockefeller. </p><p>?466 JCB VOLUME 1 B4 NUMBER A 2009 </p><p>This content downloaded from 185.2.32.106 on Tue, 24 Jun 2014 21:42:22 PMAll use subject to JSTOR Terms and Conditions</p><p>http://www.jstor.org/page/info/about/policies/terms.jsp</p></li><li><p>Text and Interview by Ben Short </p><p>bshort@rockefeller.edu </p><p>What did you work on during your postdoc? I looked at a transcription factor called </p><p>Blimp 1.1 found that it was expressed in a </p><p>progenitor population for the sebaceous </p><p>gland, which is the gland that produces the oil for the skin. When I deleted </p><p>Blimp 1 from the epidermis of mice, </p><p>they developed oily skin. We really know almost nothing about this gland, so </p><p>now I want to study how it forms. Clini </p><p>cally, it's important for acne, and there </p><p>are some human tumors that form from it. </p><p>I hope that by understanding what Blimp 1 </p><p>does, we can start to understand how </p><p>these clinical diseases arise. </p><p>I also worked on a transcription factor </p><p>called NFATcl?from the same family that I worked on in graduate school. It's </p><p>expressed in the hair follicle stem cell </p><p>compartment, and I found that it controls </p><p>the proliferation of those cells and there </p><p>fore controls hair growth. It basically puts the brakes on proliferation and allows the stem cells at the hair follicle to grow </p><p>Epidermal stem cells reside in the bulge region of the hair follicle (red), where the transcription factor NFATcl (green) keeps them from proliferating too quickly. </p><p>slowly. Then, as the cells exit the stem </p><p>cell niche, they turn off their NFATcl </p><p>expression and start to proliferate, and </p><p>that allows them to form a new hair follicle. </p><p>BECOMING INDEPENDENT </p><p>Why did you choose Yale as the place to start your own laboratory? It's a very good developmental biology department in terms of research, but it </p><p>also has a strong teaching element and </p><p>I've always enjoyed that. As I said, when </p><p>I was 12 a teacher inspired me to be a </p><p>scientist, so I think you can really stimu </p><p>late people this way. That's why I went to </p><p>graduate school actually: to teach at a </p><p>school like Furman. It was only as I went </p><p>along that I found I really enjoyed re </p><p>search as well. </p><p>Your husband has also just begun his own group at Yale. Any advice on </p><p>dealing with the "two-body"problem? You have to be as broad as possible in </p><p>your applications, and hope that multiple options will work out for the two of you. It's hard </p><p>when you're in the middle of the job search because </p><p>you have two independent careers; you're trying to fit </p><p>them into one place, and </p><p>there really aren't a lot of </p><p>mechanisms that universi </p><p>ties have come up with to </p><p>try to help. But in the end, if they really want you, </p><p>they'll make it work, and we had a number of places that made us good offers. </p><p>To have a choice was amaz </p><p>ing?I never thought that would happen. But it was </p><p>very stressful. </p><p>What's the funding situation like for you as you begin your independent career? I'm not worried about fund </p><p>ing right now. Science is hard enough without wor </p><p>rying about money! I just </p><p>work I can." </p><p>have to do the best work I can and plan ahead. I have a good startup package, and a transitional award from the NIH: the K99/R00 Pathway to Independence series. Connecticut also </p><p>has stem cell grant oppor- /y S CIG n C G ?S tunities that I'm applying , , , for at the moment. hard enough </p><p>without You were a finalist in the vvor r VI na New York Academy of L i ScienceBlavatnik about money! Awards. It must be nice I ?USt have to to get recognition this JQ j^e \^es\ early in your career. </p><p>Yeah, this was great! Be </p><p>sides fellowships, I don't know of another way that postdocs are re </p><p>warded for what they've done?usually </p><p>the credit goes to the head of laboratory. So it's a real honor to have this award. </p><p>What's up next for you in terms of projects? I want to understand how the sebaceous </p><p>gland develops, and how NFATcl is </p><p>regulated in the stem cell compartment </p><p>of the hair follicle. But I'd also like to use some of the tools that have been de </p><p>veloped in the skin?such as specific keratin promoters?to understand other </p><p>epithelia in our body. There's a lot of </p><p>epithelia that express the same keratins as skin, so we can use these genetic tools </p><p>to study those tissues as well. I want to </p><p>understand how transcription factors </p><p>regulate the development of the mam </p><p>mary gland and the thymic epithelium. These are the type of questions I like to ask: how does a tissue form and then </p><p>maintain itself? What happens in disease states? That's the overarching theme for </p><p>what I've done since graduate school, </p><p>and what I want to do now in my own </p><p>laboratory. JCB </p><p>1. Horsley, V., ?tal. 2001. J. CellBiol. 153: </p><p>329-338. </p><p>2. Horsley, V., and G. Pavlath. 2003. J. Cell Biol. </p><p>1611111-118. </p><p>3. Horsley, V., et al. 2003. Cell. 113:483-494. </p><p>4. Horsley, V., etal. 2008. Cell. 132:299-310. </p><p>5. Horsley, V., etal. 2006. Cell. 126:597-609. </p><p>PEOPLE S IDEAS THE JOURNAL OF CELL BIOLOGY 467 </p><p>This content downloaded from 185.2.32.106 on Tue, 24 Jun 2014 21:42:22 PMAll use subject to JSTOR Terms and Conditions</p><p>http://www.jstor.org/page/info/about/policies/terms.jsp</p><p>Article Contentsp. 466p. 467</p><p>Issue Table of ContentsThe Journal of Cell Biology, Vol. 184, No. 4 (Feb. 23, 2009), pp. 463-614Front MatterIn This Issue [pp. 464-465]People &amp;IdeasValerie Horsley: Getting under the Skin [pp. 466-467]</p><p>CommentMitochondrial Membrane Biogenesis: Phospholipids and Proteins Go Hand in Hand [pp. 469-472]</p><p>ReportAsymmetric Enrichment of PIE-1 in the Caenorhabditis Elegans Zygote Mediated by Binary Counterdiffusion [pp. 473-479]One-Dimensional Topography Underlies Three-Dimensional Fibrillar Cell Migration [pp. 481-490]$\text{Wld}^{\text{S}}$ Protein Requires Nmnat Activity and a Short N-Terminal Sequence to Protect Axons in Mice [pp. 491-500]</p><p>$\text{Wld}^{\text{S}}$ Requires Nmnat1 Enzymatic Activity and N16-VCP Interactions to Suppress Wallerian Degeneration [pp. 501-513]Sister Telomeres Rendered Dysfunctional by Persistent Cohesion Are Fused by NHEJ [pp. 515-526]Dbf2-Mob1 Drives Relocalization of Protein Phosphatase Cdc14 to the Cytoplasm during Exit from Mitosis [pp. 527-539]Identification of Cell Cycle: Arrested Quiescent Osteoclast Precursors In vivo [pp. 541-554]Specific Combinations of SR Proteins Associate with Single Pre-Messenger RNAs in vivo and Contribute Different Functions [pp. 555-568]Mitochondrial Outer and Inner Membrane Fusion Requires a Modified Carrier Protein [pp. 569-581]The Genetic Interactome of Prohibitins: Coordinated Control of Cardiolipin and Phosphatidylethanolamine by Conserved Regulators in Mitochondria [pp. 583-596]A Concentration-Dependent Endocytic Trap and Sink Mechanism Converts Bmper from an Activator to an Inhibitor of Bmp Signaling [pp. 597-609]Correction: Sequential Roles for Myosin-X in BMP6-Dependent Filopodial Extension, Migration, and Activation of BMP Receptors [pp. 611-611]Correction: SMK-1/PPH-4.1-Mediated Silencing of the CHK-1 Response to DNA Damage in Early C. elegans Embryos [pp. 613-613]Back Matter</p></li></ul>