Valerie Horsley: Getting under the Skin

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  • 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

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  • People & Ideas

    Valerie Horsley: Getting under the skin Valerie Horsley investigates the regulation and differentiation of stem cells

    in mammalian skin.

    Epidermal stem cells in mammalian

    skin can develop primarily along three alternative paths, differenti

    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

    scription factors is a question that first

    grabbed Valerie Horsley's interest as a

    postdoc in Elaine Fuchs' laboratory at the

    Rockefeller University. Now an assistant

    professor at Yale University, she's continu

    ing to use a powerful combination of

    mouse genetics and cell biology to study how the skin is developed and maintained.

    Before her time at Rockefeller, Horsley attended Furman University as an under

    graduate, and studied for her PhD with Grace Pavlath at Emory

    "When I got to Emory,

    I didn't know what research

    was really like. My first

    year there was a great

    learning experience/7

    University in Atlanta. In Pavlath's laboratory, she

    worked on signaling path

    ways and transcription factors regulating skeletal

    muscle development ( 1-3).

    As a postdoc, she switched

    her attention to skin, look

    ing at the functions of two

    transcription factors in

    particular: NFATc 1, which controls the exit of epider mal stem cells from their

    niche to grow new hair

    follicles (4), and Blimp 1, which regulates the differentiation of spe cific precursor cells into the sebaceous

    gland (5). We caught up with Horsley to ask her

    about these precursor stages of her career

    and her recent differentiation into an inde

    pendent group leader at Yale.

    AN EARLY START What do you think you'd be if you weren't a scientist?

    I kind of always knew I was going to be a scientist. I wanted to be a doctor when I

    was a kid, but that's because it was the only

    thing I knew you could do as a career that's

    science-y. When I was in college, I realized

    that I didn't really want to take care of sick

    people. I was more interested in how the

    body works?that's why research really

    suited me better than medicine.

    What gave you this idea at such a

    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

    esting. We did experiments, and it was a

    lot of fun. That really inspired me. From then on, I knew I wanted to be a scientist.

    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

    grade I went to the Fernbank Science Center in Atlanta, which has a science

    program. High school students attend

    one- or two-week classes in physics,

    ornithology?all these different science

    classes over the course of three months. We

    did a few experiments there. I thought clon

    ing was cool after going to this program, so

    I remember trying to clone plants for a sci

    ence fair project! When you're a kid, you

    need to come up with ideas for doing ex

    periments and I think our education system

    could be better at stimulating those ideas.

    When did you get your first proper taste

    of being in a laboratory? When I went to grad school, really. Furman

    is a very small undergraduate college, so there's not a large research enterprise.

    When I got to Emory, I didn't know what research was really like. My first

    year there was a great learning experi

    ence, I learned a ton.

    TRANSCRIPTION AND TISSUES What made you choose Grace Pavlathfs

    laboratory? I'm interested in how the body works and she was one of the only faculty members

    Valerie Horsley with her daughter, Avery.

    at Emory who was really working on tis

    sue function. She had a lot of interesting cell and developmental biology projects in the laboratory, working on skeletal

    muscle. I looked at how NFATc2, which is a transcription factor, controls muscle

    development. I identified an intermediate

    stage of muscle development, in which

    multinucleated myotubes grow larger

    by recruiting additional nuclei. NFATc2 controls that step.

    I found that a secreted factor, IL-4, is

    released from these initial myotubes and

    gives that "come fuse with me" signal. I

    also did some work on prostaglandins and

    how they control this stage of myogenesis as well. That was my first love: I still love that project!

    So why did you change fields for your postdoc? A few of my favorite faculty at Emory told

    me, "Don't change, stay in muscle devel

    opment," but I really thought it would broaden me to go to a different tissue. Bone

    development was initially what I wanted to

    do, but I also wanted to go to a large

    laboratory and work with someone that was

    famous. Skin development seemed like it had a lot of tools to study developmental questions, so I came to Rockefeller.

    ?466 JCB VOLUME 1 B4 NUMBER A 2009

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  • Text and Interview by Ben Short

    bshort@rockefeller.edu

    What did you work on during your postdoc? I looked at a transcription factor called

    Blimp 1.1 found that it was expressed in a

    progenitor population for the sebaceous

    gland, which is the gland that produces the oil for the skin. When I deleted

    Blimp 1 from the epidermis of mice,

    they developed oily skin. We really know almost nothing about this gland, so

    now I want to study how it forms. Clini

    cally, it's important for acne, and there

    are some human tumors that form from it.

    I hope that by understanding what Blimp 1

    does, we can start to understand how

    these clinical diseases arise.

    I also worked on a transcription factor

    called NFATcl?from the same family that I worked on in graduate school. It's

    expressed in the hair follicle stem cell

    compartment, and I found that it controls

    the proliferation of those cells and there

    fore controls hair growth. It basically puts the brakes on proliferation and allows the stem cells at the hair follicle to grow

    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.

    slowly. Then, as the cells exit the stem

    cell niche, they turn off their NFATcl

    expression and start to proliferate, and

    that allows them to form a new hair follicle.

    BECOMING INDEPENDENT

    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

    also has a strong teaching element and

    I've always enjoyed that. As I said, when

    I was 12 a teacher inspired me to be a

    scientist, so I think you can really stimu

    late people this way. That's why I went to

    graduate school actually: to teach at a

    school like Furman. It was only as I went

    along that I found I really enjoyed re

    search as well.

    Your husband has also just begun his own group at Yale. Any advice on

    dealing with the "two-body"problem? You have to be as broad as possible in

    your applications, and hope that multiple options will work out for the two of you. It's hard

    when you're in the middle of the job search because

    you have two independent careers; you're trying to fit

    them into one place, and

    there really aren't a lot of

    mechanisms that universi

    ties have come up with to

    try to help. But in the end, if they really want you,

    they'll make it work, and we had a number of places that made us good offers.

    To have a choice was amaz

    ing?I never thought that would happen. But it was

    very stressful.

    What's the funding situation like for you as you begin your independent career? I'm not worried about fund

    ing right now. Science is hard enough without wor

    rying about money! I just

    work I can."

    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

    has stem cell grant oppor- /y S CIG n C G ?S tunities that I'm applying , , , for at the moment. hard enough

    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.

    Yeah, this was great! Be

    sides fellowships, I don't know of another way that postdocs are re

    warded for what they've done?usually

    the credit goes to the head of laboratory. So it's a real honor to have this award.

    What's up next for you in terms of projects? I want to understand how the sebaceous

    gland develops, and how NFATcl is

    regulated in the stem cell compartment

    of the hair follicle. But I'd also like to use some of the tools that have been de

    veloped in the skin?such as specific keratin promoters?to understand other

    epithelia in our body. There's a lot of

    epithelia that express the same keratins as skin, so we can use these genetic tools

    to study those tissues as well. I want to

    understand how transcription factors

    regulate the development of the mam

    mary gland and the thymic epithelium. These are the type of questions I like to ask: how does a tissue form and then

    maintain itself? What happens in disease states? That's the overarching theme for

    what I've done since graduate school,

    and what I want to do now in my own

    laboratory. JCB

    1. Horsley, V., ?tal. 2001. J. CellBiol. 153:

    329-338.

    2. Horsley, V., and G. Pavlath. 2003. J. Cell Biol.

    1611111-118.

    3. Horsley, V., et al. 2003. Cell. 113:483-494.

    4. Horsley, V., etal. 2008. Cell. 132:299-310.

    5. Horsley, V., etal. 2006. Cell. 126:597-609.

    PEOPLE S IDEAS THE JOURNAL OF CELL BIOLOGY 467

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    Article Contentsp. 466p. 467

    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 &IdeasValerie Horsley: Getting under the Skin [pp. 466-467]

    CommentMitochondrial Membrane Biogenesis: Phospholipids and Proteins Go Hand in Hand [pp. 469-472]

    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]

    $\text{Wld}^{\text{S}}$ 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