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SDRC Spotlight — Summer 2009
News from the
UAB Skin Diseases Research Center
Issue 14
DEPARTMENT OF DERMATOLOGY SDRC SPOTLIGHT
Department
of Dermatology
Mail: EFH 414, Zip 0009
Web: www.uab.edu/derm
Phone: 205-934-5188
SDRC Personnel
Craig Elmets, M.D.— Director
David Chaplin, M.D., Ph.D. Co-Director
Mohammad Athar, Ph.D. Co-Director
Laura Timares, Ph.D. — Core B
William Grizzle, M.D., Ph.D. — Core C
Stephen Barnes, Ph.D. — Core D
Helen Kim, Ph.D.—Co-Director, Core D
Joel Glasgow, Ph.D. — PF 11
Amy Theos, M.D. — PF 12
Louise Chow, Ph.D.—PF 13
Nabiha Yusuf, Ph.D.—PF 14
Laurie Harrington, Ph.D. PF 15
Jennifer Frank — Administrator
Inside this issue:
SDRC Competitive
Renewal is funded for
five years
1
New Research Awards
2
Society for Investigative
Dermatology
3
Ongoing Clinical Trails
4
Training Grant Slot
Available
4
PAGE 1
SDRC Competitive Renewal
Funded from 2009 - 2014
The competitive renewal application for the Skin Diseases Research
Center (SDRC), submitted in July
2008, has been funded! It is one of
only six such centers in the country
and will continue to serve as an interdisciplinary center of excellence in
Investigative Dermatology.
The
SDRC has grown to include 39 investigators from 14 different departments within UAB.
The renewal application had four
thematic emphases: 1) immunodermatology and cutaneous microbiology; 2) skin cancer; 3) biochemistry
of the skin: and 4) genetics and developmental biology. Three Core
facilities serve the needs of SDRC
investigators: 1) Skin Cell Culture
Core (Laura Timares Ph.D., PI); 2)
Tissue Resources and Molecular
Pathology (William Grizzle, M.D.,
PI); and 3) Skin Proteomics
(Stephen Barnes, Ph.D., PI). These
cores continue to provide SDRC
members with the most current services, equipment, training and consultation and to do so in an efficient
and cost-effective manner.
The SDRC also supports a highly
successful Pilot and Feasibility program, with 11 studies funded to
date. For the new application, three
studies were selected from nine that
applied. These studies highlight the
diversity of interest in skin research
SDRC Director, Craig Elmets, M.D.
(center), and co-Directors, Mohammad
Athar, Ph.D. (left) and David Chaplin,
M.D., Ph.D. (right)
within the UAB community.
The
studies are: Human induced pluripotent stem cells to investigate inherited skin diseases (Louise Chow,
Ph.D., PI); Role of the innate immune system in regulation of UVB
induced skin carcinogenesis (Nabiha
Yusuf, Ph.D., PI); and Investigating
the requirement for Tbet expression
during psoriasis (Laurie Harrington,
Ph.D., PI).
A vibrant Enrichment and Communications Program will continue to
support speakers from inside and
outside of UAB. The activities of the
SDRC are administered by the Administrative Core, which is also responsible for continuing scientific
development and strategic planning.
The Director is Craig Elmets, M.D.,
and the co-Directors are Mohammad
Athar, Ph.D., and David Chaplin,
M.D., Ph.D. Jennifer Frank will continue to serve as the administrator.
ISSUE 14
DEPARTMENT OF DERMATOLOGY SDRC SPOTLIGHT
PAGE 2
Dermatology Grant News
New Awards
Despite the challenging funding climate, the Department of Dermatology maintains an outstanding
portfolio of external research support. Department
scientists currently hold three NIH R01 grants and
two VA Merit Review awards. In addition, Drs.
Laura Timares and Mohammad Athar recently competed successfully for grants from the NIH and Dr.
Nabiha Yusuf received a Career Development
Award from the Dermatology Foundation.
Dr. Timares will study the molecular effects of UV
photodamage on skin cells. In response to photodamage, skin carries out a number of processes
that protect it against cancer development; orchestration of these processes is quite complicated. At
the same time, mildly damaged cells are repaired
(DNA repair pathways are activated) and UVmutated oncogenic cells are eliminated (apoptosis
cascades are activated). Dr. Timares will study Bid,
a “BH3-only” member of the Bcl-2 family that appears to possess both prosurvival and proapoptotic
functions. In particular, Dr. Timares proposes that
the same protein can perform such distinct functions by virtue of undergoing two very different
modifications. She hypothesizes that phosphorylated Bid (pBid) acts in the cell nucleus in a prosurvival fashion and that a truncated form of Bid (tBid)
acts in the mitochondrion to support apopotosis.
Dr. Timares will pursue two aims in her R21
grant. First, she will examine the mechanisms by
which Bid promotes DNA repair in UVB-damaged
skin cells. In both mouse and human cells, Dr. Timares will determine the extent to which pBid promotes cell cycle checkpoint activity for regulating
DNA repair (see figure). She will also evaluate how
Bid itself is regulated by the UV-DNA damage
kinase ATR and p53, two proteins known to be important in the DNA repair process. Her second aim
will be to create a new mouse model in which Bid is
deficient in order to determine whether this affects
the development of UV-induced cutaneous tumors.
This work is quite clinically relevant in that UV from
sunlight is a potent carcinogen by virtue of causing
DNA mutations. Thus, the results of her studies
may help in developing strategies to control skin
cancer and give rise to new diagnostic and therapeutic applications.
Nabiha Yusuf, Ph.D. also studies effects of UVB
on skin cells, specifically the mechanisms of UVinduced non-melanoma skin cancer. Toll-like receptors (TLRs) are present on skin cells and are important in the initial anti-oncogenic immune responses.
Dr. Yusuf hypothesizes that UVB radiation activates
TLR signaling pathways, thus suppressing the immune response and allowing skin cancer development. Specifically, her preliminary data indicate that
TLR4, a particularly critical TLR, may work to encourage production of so-called “regulatory T-cells”
that inhibit the development and/or function of other
types of T-cells that eradicate tumors. Dr. Yusuf’
will use her grant to compare mice deficient in
TLR4 with those that have a functional TLR4 gene
to assess the abundance and characteristics of
regulatory T-cells that develop after UVB radiation
in the two mouse models. Importantly, she will also
determine whether the TLR4-deficient mice, which
are more resistant to UVB-induced immune suppression develop tumors when chronically exposed
to UVB radiation. This work will add important information about the nature of UVB-induced skin cancer and potential genetic susceptibility markers
and/or targets for prevention or therapy.
UVB induced nuclear phosphorylation of Bid occurs independent of p53 in the
human SCC line A253 cells. Parental p53 negative and p53 transfected A253
cells were exposed to UVB radiation and examined after 6 hours of culture.
Immunofluorescent staining of DNA by DAPI is shown in blue; PCNA nuclear
staining patterns, shown in red, indicate the cell cycle phase as shown. (Early S
pattern - speckled; mid S - accumulation of PNCA at the nuclear membrane; late
S - patchy distribution, late G2/M - suggested by nuclear bifurcation. pBid staining is green and intensifies in late S-G2/M phases in a UVB dose-dependent
manner (note reduced pBid staining following 20 mJ/cm2 as compared to cells
treated with 60mJ/cm2.)
ISSUE 14
DEPARTMENT OF DERMATOLOGY SDRC SPOTLIGHT
PAGE 3
Society of Investigative Dermatology
May 6-9, 2009
The Society of Investigative Dermatology,
the most prestigious organization for research
in cutaneous biology, held its 69th annual
meeting in Montreal, Canada on May 6-9,
2009. The UAB Department of Dermatology
was well represented with eight scientists attending, Out of fourteen presentations, six
were recognized by invitations for oral presentation. Many of the submissions reflect the cooperation and collaboration that characterize
the Department scientists. The posters are
classified by topic.
Clinical Research and Therapeutics
studies in the area of Carcinogenesis. Dr.
Santosh Katiyar, Ph.D. presented a talk on the
research in his laboratory investigating a possible role of IL-12 in the treatment or prevention
of skin tumors and angiogenesis. Lastly, Dr.
Chao-Cheng Wang, the Departmental expert in
proteomics, presented a poster on “Differential
proteomic analysis of the effects of immunosuppressant, Cyclosporinte A and rapamycin,
on squamous cell carcinoma by 2D difference
gel electrophoresis and mass spectrometry”.
Adaptive Immunity
The Department submitted two abstracts in
the area of Clinical Research and Therapeutics. The first with Craig Elmets, M.D., Chair,
as first author was an oral presentation on the
results of a Phase II/III clinical trial examining
the effects of celecoxib on non-melanoma skin
cancer. The second was authored by Wendy
Cantrell, C.R.N.P. (with Dr. Elmets as senior
investigator) and reports a study of the natural
course of actinic keratoses over an 11 month
period.
Dr. Hui Xu, Ph.D. (Associate Professor), the
Department expert in contact hypersensitivity,
was senior author on the submission “Cd5 is
expressed by dendritic cells and is a coinhibitory molecule for T cell activation and immune responses” given as an oral presentation
by Dongou He (postdoctoral fellow). Also in
the area of adaptive immunity, Nabiha Yusuf,
Ph.D. (Instructor) presented “Heat shock proteins-27 and –70 have a functional role in cutaneous and cell-mediated immune responses
through effects on dendritic cells.
Carcinogenesis
Photobiology
Four abstracts from the Department were in
the area of Carcinogenesis. The Laboratory of
Laura Timares, Ph.D. presented an abstract
entitled “A novel role for Bid in promoting UVinduced cell cycle checkpoint function and suppression of skin carcinogenesis.” with Hee
Kyung Kim, Ph.D. (Postdoctoral Fellow) as first
author. Dr. Mohammad Athar’s laboratory was
represented by Stephanie Beatrous, M.D., a
fellow on the Department’s NIH T32 training
grant, who delivered an oral presentation on
the laboratory’s work on “Cyclosporine A
(CsA), an immunosuppressant, transforms
squamous cell carcinoma to a more invasive
phenotype: a non-immunological effect”. Dr.
Athar was also a contributor to several other
The Department’s submission in the area of
photobiology was an oral presentation by Syed
Meeran, Ph.D. (postdoctoral fellow) from Dr.
Katiyar’s lab and was entitled “Inhibition of angiogenesis in UV-induced skin tumors by drinking green tea polyphenols requires IL-12”.
Pigmentation
In this area, Aton Holzer, M.D. (T32 training
grant fellow) presented “IL-12/23 suppresses
the growth of melanocytic nevi in mice” with Dr.
Elmets as senior author.
ISSUE 14
DEPARTMENT OF DERMATOLOGY SDRC SPOTLIGHT
UAB Department of Dermatology
CLINICAL TRIALS
Are your patients interested in free
treatment through a clinical study?
Do you have any patients
with the following?
Cutaneous T-cell Lymphoma
Epidermolysis Bullosa
Hand Dermatitis
Onychomycosis
Post-Herpetic Neuralgia
Psoriasis
Seborrheic Dermatitis
Tinea Versicolor
We also have two long-term
follow-up studies including:
ATLAS (for patients
already on Amevive)
PSOLAR (for patients on biologic
therapies for psoriasis)
Contact the UAB Dermatology clinical
research office at (205) 502-9960 / 9962
for more information or to make a referral.
PAGE 4
Postdoctoral Fellowship
Investigative Dermatology
The Department of Dermatology at
the University of Alabama at Birmingham is seeking a candidate for a T32
training grant in investigative dermatology and cutaneous biology beginning
July 1, 2010. The incumbents should
have an M.D., Ph.D., M.D./Ph.D., or the
equivalent and must be an American citizen or permanent resident.
The program will provide interdisciplinary training to talented individuals who
are interested in becoming independent
researchers in the area of skin carcinogenesis, cell cycle regulation, signaling
pathways regulating proliferation
(particularly sonic hedgehog signaling)
and development of suitable murine
models.
In addition to mentor based research
projects, trainees will participate in didactic activities that will strengthen the
intellectual foundation required for innovative dermatological projects and will
receive rigorous instruction in the principles necessary for ethical research.
Further information can be obtained
from Jennifer Frank at (205) 975-6415.
Interested candidates should forward
their CV to Craig Elmets, M.D., Professor and Chairman, Department of Dermatology, via mail at EFH 414, 1530 3rd
Avenue South, Birmingham, AL 352940009, or through email at [email protected].