# 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

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,

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

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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