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PASPCR
August 2013
1
The PASCR Web-Site can be found at:
http://www.paspcr.org
The PASPCR Newsletter is published three times a
year and is intended to serve as a regular means of
communication for the members of our Society. The
PASPCR Newsletter is distributed via e-mail, in pdf
format, on the first of April, August and December and
it will continue to be posted on the web-site of the
Society.
Preparations for 18th
PASPCR Meeting, spear-
headed by Dr. Vijayasaradhi Setaluri, are progressing
well. The meeting will be held in Madison,
Wisconsin, from September 8th to September 11
th, 2013.
Further information on the meeting can be found on
pages 7-11 of this newsletter. In this issue, we continue the “Laboratory Updates”
section with a column by Dr. Gisela Erf. We also
continue the “Industry Perspectives” section with a
column by Dr. Gertrude-Emilia Costin, and the
“Clinical Insights” section with a column by Dr. Reza
Nejati.
We hope you enjoy this issue. We encourage you to
send us your comments at our email address
[email protected]. Let us know what you
would like to see in the letters, suggest sections you
think would be useful to include, and recommend any
changes that you would like to see.
We also encourage you to let us know about
meetings that you think would be of interest to members
of the Society. If you attend a scientific meeting at
which you heard about work which you think will be of
interest to the membership of the PASPCR, please write
a few paragraphs summarizing what was presented and
share it with us. If you know of training courses that
would be of interest to the PASPCR members, please let
us know and we will add them to a new section in our
Calendar of Events.
Also, keep us updated on any “Members in the
News” so we can spread the word of your successes.
This is your Newsletter, and we depend upon you to
help us ensure it best serves the Society’s needs. We
look forward to hearing your ideas and suggestions and
to continue working together to compile the Newsletters
for our Society.
The PASPCR Newsletter Editorial Team would like
to thank all our contributors for their columns submitted
to us for inclusion in the letters.
PASPCR Newsletter Editorial Team
PASPCR Newsletter August 2013
Vol. 21 Number 2
In this Issue . . . . PASPCR OFFICERS 2
CALENDAR OF EVENTS 2
CORPORATE SPONSORS 3
MEMBERSHIP UPDATES 3
PASPCR PRESIDENT’S CORNER 5
LETTER FROM THE PASPCR SECRETARY/TREASURER 6
18th PASPCR MEETING 7
The Venue 7
Scientific Program 9
Key Dates 11
Sponsors of the Meeting 11
PCMR JOURNAL CORNER 11
PCMR Journal – New Impact Factor 11
MEETINGS ANNOUCEMENTS 12
22nd IPCC 12
HUSCRI SKIN OF COLOR SYMPOSIUM 13
PIGMENTATION COMMUNITY CONNECTIONS 14
LABORATORY UPDATES 15
by Dr. Gisela Erf
INDUSTRY PERSPECTIVES 18
by Dr. Gertrude-Emilia Costin
CLINICAL INSIGHTS 21
by Dr. Reza Nejati
MEMBERS IN THE NEWS 24
PASPCR Members Featured in Yale News, June 26, 2013 24
POSITIONS WANTED/AVAILABLE 24
PASPCR
August 2013
2
C/O Andrzej T. Slominski, M.D., Ph.D.
University of Tennessee Health Science Center
Department of Pathology and Laboratory Medicine
930 Madison Avenue, Room 525 (Clinical Office)
Memphis, TN 38163, U.S.A.
Officers:
Greg Barsh President
Caroline Le Poole President-elect
Andrzej Slominski Secretary/Treasurer
Council Members: Gertrude-Emilia Costin (2012-2014)
Thomas Hornyak (2013-2015)
Lidia Kos (2013-2015)
Deborah Lang (2011-2013)
Sancy Leachman (2012-2014)
John Pawelek (2011-2013)
Glynis Scott (2012-2014)
Vijayasaradhi Setaluri (2011-2013)
Julio Valencia (2013-2015)
IFPCS Representatives:
Andrzej Slominski (Secretary)
Greg Barsh (Council Member)
Frank Meyskens (Council Member)
CALENDAR OF EVENTS
2013
The 18th ESPCR Meeting
Date and place: September 9-12, Lisbon, PORTUGAL
Web-site: http://www.espcr.org/ESPCR2013/
2013
The 18th PASPCR Meeting
Date and place: September 8-11, Madison, WI, USA
Web-site: www.paspcr.org/
2013
HUSCRI Skin of Color Symposium 2013
Date and place: October 25-27, Baltimore, MD, USA
Web-site: http://huscri.org/symposium/
2013
The Annual Meeting of American Society for Cell Biology
Date and place: December 14-18, New Orleans, LA, USA
Web-site: http://www.ascb.org/
2014
The 22nd IPCC
Date and place: September 4-7, Singapore, SINGAPORE
Web-site: http://www.ipcc2014.org/
The PASPCR Newsletter is published three times a year (April, August and December) by the PanAmerican Society for
Pigment Cell Research. All views are those of the authors. For further information or to submit articles, please use the
e-mail address [email protected].
Publication Committee
Gertrude-Emilia Costin, Ph.D., M.B.A.
Editor Institute for In Vitro Sciences, Inc. (IIVS)
30 W. Watkins Mill Road #100 Gaithersburg, MD 20878, U.S.A.
(301) 947-6524
Prashiela Manga, Ph.D.
Associate Editor New York University School of Medicine
Department of Dermatology
Smilow Research Center 522 First Avenue, Room 401
New York, NY 10016, U.S.A.
(212) 263-9086 [email protected]
William S. Oetting, Ph.D.
University of Minnesota
Department of Medicine - Genetics
MMC 485; 4-12 Moos Tower
515 Delaware Street S.E.
Minneapolis, MN 55455, U.S.A.
(612) 624-1139
Andrzej T. Slominski, M.D., Ph.D. University of Tennessee Health Science Center
Department of Pathology and Laboratory Medicine 930 Madison Avenue, Room 525 (Clinical Office)
Memphis, TN 38163, U.S.A.
(901) 448-3741 [email protected]
The PanAmerican Society for
Pigment Cell Research
PASPCR
August 2013
3
CORPORATE SPONSORS
by Dr. Andrzej Slominski
The PASPCR would like to acknowledge
and thank our Sponsors. The list below reflects
contributions made during the year of 2012. In
the past, financial gifts from our Sponsors have
allowed our Society to increase benefits to the
membership far out of proportion to the actual
dues collected from members. We gratefully
acknowledge the contributions for the 17th
PASPCR Meeting made through PASPCR as
follows (in alphabetical order):
All Resort Transportation
Department of Dermatology at the University
of Utah
Huntsman Cancer Institute at the University
of Utah
Johnson & Johnson Consumer Companies
(Aaron B. Lerner Lecture)
Merck
Morphotek
Myriad Genetics
Prometheus
St. Regis Hotel
- // -
MEMBERSHIP UPDATES
Renewals
Michael G. Anderson
University of Iowa
Iowa City, IA, USA
Raymond E. Boissy
University of Cincinnati
Cincinnati, OH, USA
Sreenivasulu Chintala
Roswell Park Cancer Institute
Buffalo, NY, USA
John A. D'Orazio
University of Kentucky College of Medicine
Lexington, KY, USA
Howard A. Epstein
EMD Chemicals
Philadelphia, PA, USA
David Fisher
Harvard Medical School Boston, MA, USA
Deborah Lang
University of Chicago
Chicago, IL, USA
Julian M. Menter
Morhouse School of Medicine
Atlanta, GA, USA
William J. Pavan
National Institutes of Health Bethesda, MD, USA
Joel Pinczewski
University of Maryland
Owings Mill, MD, USA
Javier Pino
Florida International University
Miami, FL, USA
Archit Trivedi
Toledo, OH, USA
PASPCR
August 2013
4
New Members
Nihal Ahmad
University of Wisconsin Madison, WI, USA
Mark R. Albertini
University of Wisconsin
Madison, WI, USA
Amanda Decker
University of Iowa
Iowa City, IA, USA
Adam M. Hammer
Loyoula University Chicago Maywood, IL, USA
Adam Hedberg-Buenz
University of Iowa
Iowa City, IA, USA
Daniel P. Kestler
University of Tennessee
Knoxville, YN, USA
Himangi Marathe University of Toledo
Toledo, OH, USA
Katsuo Matsumoto
POLA Chemical Industries, Inc. Totsuka-ku
Yokohama, JAPAN
Gaurav Mehta
University of Toledo
Toledo, OH, USA
Tahseem H. Nasti
University of Alabama Birmingham, AL, USA
Amy Saldana
Florida International University
Miami, FL, USA
Hannah Seberg
University of Iowa
Iowa City, IA, USA
Laura Timares
University of Alabama Birmingham, AL, USA
Xiaoqi Wang
Northwestern University Feinberg School of
Medicine
Chicago, IL, USA
Maria L. Wei
UCSF San Francisco, CA, USA
Sunghan Yim
Avon Products, Inc.
Suffern, NY, USA
Update
Sancy Leachman
New E-mail Address: [email protected]
- // -
PASPCR
August 2013
5
PASPCR PRESIDENT’S CORNER
We are still a few months away from
Autumn, but I find myself feeling somewhat
autumnal, in part because my term as PASPCR
President will finish this year, in part because
the continued sorry state of US science funding
heralds a very cold spell for important advances
in basic research, and in part because of my own
midlife, er, catharsis.
Helping to lead PASPCR has been terrific,
but I wish I could do more. Like other scientific
societies, we continue to face a diversity of
challenges, yet manage to hang on as a
community of colleagues with shared interests,
and, often, as friends. I continue to believe that
for our Society to flourish (perhaps even to
survive), we must identify areas that will attract
and excite young scientists, consider new ways
of communicating that are not tied to publishing
companies, and look to our sister Societies for
alliances that offer synergy and strength.
Perhaps these issues can be discussed informally
next month in Madison, in ways that will
energize and invigorate, and maybe even
expand, our group and our comfort zones.
Of course, the biggest challenge we face is
the increasingly grim outlook for NIH funding.
Caught in a perfect storm of a national economy
that is still stumbling, NIH priorities that
threaten individual investigators funded by RO1
grants, and a political landscape poisoned by
bickering and ignorance, it’s hard to stay
optimistic. One bright spot is the Society itself -
speaking with many of you by phone or by email
over the last several months, I sense the same
curiosity, critical thinking, and fascination with
biology that characterized the Pigment Cell
Societies at their inception, and that continues, I
think, to motivate all of us. Another bright spot,
for me at least, is genomics. The same
technological advances that feed “big biology”
can, perhaps ironically, be applied to systems
and questions that were previously inaccessible.
I’m reminded of a quote from Sydney Brenner:
“Progress in science depends on new techniques,
new discoveries, and new ideas, probably in that
order”. Ideas may be our currency, but their
value depends heavily on implementation, and I,
for one, continue to be amazed at the ways in
which genomic technology can be applied to
new questions.
What about that midlife crisis? While other
middle aged pigment cell biologists have ended
up in small sports cars, I decided to get a big
telephoto lens, which was put to good use after
the IFPCS Special Interest Developmental
Biology Meeting earlier this year. Ian Jackson
and Liz Patton organized a wonderful 3 days of
science and science friends, and did so in the
amazing city of Edinburgh. It was my first real
visit to Scotland, and I took full advantage of the
opportunity to spend an extra 3 or 4 days
wandering through the Scottish Highlands.
There was a bit of whisky tasting, but I spent
most of my time in search of warm-blooded
pigmentary diversity apparent in Atlantic
Puffins, Northern Gannets, and, a spectacular
King Eider, courtesy of an insider
recommendation from Robert Kelsh. The only
thing more exciting than seeing these animals in
their natural environment is the opportunity to
capture and share their images, which I hope to
do with many of you this Fall in Madison.
Greg Barsh, M.D., Ph.D.
PASPCR President
- // -
PASPCR
August 2013
6
LETTER FROM THE PASPCR
SECRETARY/TREASURER
Dear PASPCR members,
The date of the XVIIIth
PASPCR meeting
in Madison, Wisconsin (see
http://www.paspcr.org/paspcr2013/index.php) is
approaching very fast and I urge all members of
the PASPCR or investigators interested in the
pigment cell biology to attend this meeting.
Those who want to present their latest work can
still submit it as a late breaking abstract till
August 15, 2013. The Organizing Committee
under the leadership of Dr. Vijayasaradhi
Setaluri has prepared an outstanding scientific
program that is well balanced and focusses on
the Advances in Melanocyte and Melanoma
Biology. It is marked by excellent speakers
invited by the organizers, and is supplemented
by excellent oral presentations selected from the
submitted abstracts. Of note is the Key Note
lecture by Dr. Hector DeLuca entitled “The
Vitamin D Story, From Basic Science to the
Clinic”. Dr. DeLuca is a distinguished
investigator, member of the National Academy
of Science, USA and recipient of many awards
who built the foundations for modern research
on vitamin D and its clinical application.
Vitamin D is an extremely important molecule
that, in addition to regulating calcium body
homeostasis, expresses several other
bioregulatory functions both on systemic and
local (skin) levels. Here I would like to add that
during the PASPCR meeting in Memphis, Dr.
Holick, a trainee of Dr. DeLuca, also presented
on vitamin D and its crucial role in physiology.
Furthermore, Dr. David E. Fisher, Chairman
of the Department of Dermatology, MGH,
Harvard Medical School, will present the Aaron
B. Lerner Lecture entitled “From MITF to
Redheads and Associated Phenotypes”. Dr.
Fisher is a member of our Society in good
standing and we cherish his membership in the
PASPCR.
Importantly, having residual funds raised for
the PASPCR meeting in Memphis we are
planning to grant 16-17 travel grants in the
amount of $500 per award. These will be
distributed predominantly to postdocs and
students to attend the PASPCR meeting in
Madison, WI. The awards will be based on the
eligibility and scientific soundness of the
abstracts as determined by the Scientific
Committees. To be eligible, the recipient has to
be a member of the PASPCR, be first and
presenting author and the priority will be given
to students and postdoctoral fellows.
During the meeting a new
Secretary/Treasurer will be selected, since the
current Secretary/Treasurer is serving the sixth
year on this position, a maximum allowed by the
PASPCR bylaws. However, Dr. Slominski will
continue to serve as Council member for next 2
years (2014-2015), and will represent our
Society as the Secretary of the IFPCS till the end
of 2014.
We are also acknowledging the support of
Johnson and Johnson ($5,000) to cover the costs
connected with Aaron B. Lerner lecture. We also
acknowledge the sponsorship of the Conference
by Merck ($2,500), Janssen ($1,500) and
Daavlin ($1,000).
We hope that you will be able to attend this
meeting, which will not only cover many aspects
of pigment cell biology from basic to clinical
science, but also other areas of life science such
as role of vitamin D in biomedical research and
medicine. Therefore, please mark your calendar
for September 8-11, 2013 to attend the XVIIIth
PASPCR meeting in Madison, Wisconsin.
I also provide some statistics on the
membership. The total number of current
members in good standing is 123, which
includes 31 student members, 2 members of
Japanese and 2 members of the European
Society, and 5 members of the SMR.
Thank you again for your support of our
Society and I am looking forward to see you in
Madison!
Andrzej Slominski, MD, PhD
Professor of Pathology and Medicine
Secretary/Treasurer of the PASCPR and
Secretary of the IFPCS
PASPCR
August 2013
7
18th
PASPCR MEETING
September 8th
– September 11th
, 2013, MADISON, WI, USA
PASPCR
August 2013
8
PASPCR
August 2013
9
Scientific Program
Sunday, September 8, 2013
6:00pm – 9:00pm Reception & Registration
Monday, September 9, 2013
8:00am – 8:30am Breakfast
8:30am – 8:45am Welcome and opening remarks
Drs. Vijay Setaluri and Greg Barsh
8:45am – 8:50am Introduction of Keynote Speaker
Dr. Gary Wood
8:50am – 9:50am Keynote Lecture: The Vitamin D Story, From Basic Science to the Clinic Dr. Hector F. DeLuca, University of Wisconsin, Madison
9:50am – 10:00am Break
10:00am – 12:30pm Plenary Session I: Melanocyte Development & Melanoma Cancer Stem
Cells
10:00am – 10:30am Invited Lecture: Neurofibromin Gene Dosage and Melanocyte Development
Dr. Catherine Van Raamsdonk, University of British Columbia, Vancouver,
British Columbia, Canada
10:30am – 11:00am Invited Lecture: Phenotypic Heterogeneity in Tumorigenic Melanoma Cells
Dr. Elsa Quintana, OncoMed Pharmaceuticals, Redwood City, CA
11:00am – 11:45am Oral session 1: Melanocyte development
(3 talks from selected abstracts, 12 min plus 3 min discussion)
11:45am – 12:30pm Oral session 2: Melanoma tumor initiating cells
(3 talks from selected abstracts, 12 min plus 3 min discussion)
12:30pm – 1:30pm Lunch
1:30pm – 2:30pm Poster Session I
2:30pm – 5:15pm Plenary Session II: Melanocyte UV Response and Mouse Melanoma
Models
2:30pm – 3:00pm Invited Lecture: MC1R and Melanocyte Response to UV
Dr. Zalfa Abdel-Malek, University of Cincinnati, Cincinnati, OH
3:00pm – 3:30pm Invited Lecture: Genetic Mouse Models of Pigmentation and Melanoma
Dr. Marcus Bosenberg, Yale University, New Haven, CT
3:30pm – 3:45pm Break
3:45pm – 4:30pm Oral session 3: UV and skin pigmentation
(3 talks from selected abstracts, 12 min plus 3 min discussion)
4:30pm – 5:15pm Oral session 4: Animal models
(3 talks from selected abstracts, 12 min plus 3 min discussion)
PASPCR
August 2013
10
5:15pm – 6:15pm Poster session II with wine & cheese
Tuesday, September 10, 2013
8:00am – 9:00am Breakfast with experts: Opportunities and Challenges in Pigment Cell Research
A Q&A session for aspiring graduate students and postdocs
9:00am – 11:45am Plenary Session III: Cell & Molecular Biology of Normal & Malignant
Melanocytes
9:00am – 9:30am Invited Lecture: Fly Eye Pigmentation and Human Disease
Dr. Esteban Dell'Angelica, University of California, Los Angeles
9:30am – 10:00am Invited Lecture: ATF2, At the Crossroad of Nuclear and Cytosolic Functions
Dr. Ze'ev Ronai, Sanford-Burnham Medical Research Institute, La Jolla, CA
10:00am – 10:15am Break
10:15am – 11:00am Oral session 5: Biology of melanin pigmentation
(3 talks from selected abstracts, 12 min plus 3 min discussion)
11:00am – 11:45am Oral session 6: Biology of malignant melanocytes
(3 talks from selected abstracts, 12 min plus 3 min discussion)
11:45am – 12:30pm Poster session III
12:30pm – 1:30pm Lunch
1:30pm – 2:30pm Aaron Lerner Award Lecture: From MITF to Redheads and Associated
Phenotypes Dr. David Fisher, Harvard Medical School, Boston, MA
2:30pm – 5:15pm Plenary Session IV: Immune Responses to Normal & Malignant
Melanocyte
2:30pm – 3:00pm Invited Lecture: Dissection of T Cell Responses in Vitiligo
Dr. José A. Guevara-Patiño, Loyola University Medical Center, Chicago, IL
3:00pm – 3:30pm Invited Lecture: Genetics of Vitiligo
Dr. Richard Spritz, University of Colorado, Denver
3:30pm – 3:45pm Break
3:45pm – 4:30pm Oral session 7: Pathobiology of vitiligo
(3 talks from selected abstracts, 12 min plus 3 min discussion)
4:30pm – 5:15pm Oral session 8: Melanocyte antigens in melanoma immune response
(3 talks from selected abstracts, 12 min plus 3 min discussion)
5:15pm – 6:00pm Poster session IV
6:30pm Gala Dinner
PASPCR
August 2013
11
Wednesday, September 11, 2013
8:00am – 9:00am Breakfast with experts: Opportunities and Challenges in Pigment Cell &
Melanoma Research
A Q&A session for aspiring graduate students and postdocs
9:00am – 11:45am Plenary Session V: Bench-to-Bedside & Back
9:00am – 9:30am Invited Lecture: Melanoma Next-generation Sequencing, Biological
Significance and Clinical Applications
Dr. Ruth Halaban, Yale University School of Medicine, New Haven, CT
9:30am – 10:00am Invited Lecture: Survival in BRAF V600-mutant Advanced Melanoma Patients
Dr. Jeff Sosman, Vanderbilt-Ingram Cancer Center, Nashville, TN
10:00am – 10:15am Break
10:15am – 11:00am Oral session 9: Malignant transformation of melanocytes
(3 talks from selected abstracts, 12 min plus 3 min discussion)
11:00am – 11:45am Oral session 10: Drug resistance of melanoma
(3 talks from selected abstracts, 12 min plus 3 min discussion)
11:45am – 1:00pm Poster session V
1:00pm – 2:00pm Lunch & Departure
Key Dates
Early Registration Rates extended until August 15th
, 2013
Late Breaking Abstracts for Poster Session only can be submitted until August 15th
, 2013
Sponsors of the Meeting
Johnson & Johnson
Merck
Janssen
Daavlin
Nikon
- // -
PCMR JOURNAL CORNER
The PCMR Journal announced in July its new Impact Factor of PCMR: 5.839!
The journal is growing and thriving thanks to an amazing professional commitment of its editors,
reviewers and authors to constantly improve and develop the journal.
PASPCR
August 2013
12
22ND
INTERNATIONAL PIGMENT CELL CONFERENCE
September 4th
– September 7th
, 2014, SINGAPORE
The 22nd
International Pigment Cell Conference (IPCC) will be held from 4th
to 7th
September
2014 in Asia’s top convention city, Singapore. Hosted by the Asian Society for Pigment Cell Research
(ASPCR), in partnership with the Dermatological Society of Singapore (DSS), this triennial meeting of
the International Federation of Pigment Cell Societies will be held in conjunction with the 27th
Annual
Scientific Meeting of the DSS.
IPCC 2014 has been themed “Bringing Colours to Life” as it aims to capture the vibrant
advancements in pigment cell research and their applications in dermatology and clinical medicine.
Distinguished researchers, clinicians as well as young investigators will be sharing the leading
advances in basic and translational research in pigment cell biology and melanoma, and address the
burden of pigmentary disorders across Asia. The organizers believe that this important event offers an
excellent opportunity for the exchange of ideas among clinicians and scientists and fosters international
collaboration.
Apart from offering you an outstanding scientific program, the organizers invite the participants
to experience Singapore, a bustling cosmopolitan city-state with a unique blend of modernity and
traditional charm. Home to a vibrant, multi-cultural society and a multitude of award-winning
attractions, this beautiful city will undoubtedly enrich your overall experience.
Organizers:
Dr. Boon-Kee Goh, Organizing President - IPCC 2014
Dr. Su-Ni Wong, President - Dermatological Society of Singapore
Dr. Mauro Picardo, President - International Federation of Pigment Cell Societies
PASPCR
August 2013
13
2013 SKIN OF COLOR SYMPOSIUM
October 25th
– October 27th
, 2013, BALTIMORE, MD, USA
The 2013 Skin of Color Symposium will be held October 25-27, 2013 in Baltimore’s charming and
dynamic Inner Harbor at the Royal Sonesta Harbor Court Hotel. The symposium is designed for
dermatologists, plastic surgeons, primary care physicians, physician assistants, residents, students and
professionals with an interest in skin research in skin of color. The objectives of the symposium are to
identify, diagnose and treat rare or serious dermatological diseases that are more prevalent in skin of
color and to translate research about dermatological diseases that are most commonly seen in skin of
color and to apply those findings to clinical practice.
This activity has been planned and implemented in accordance with the Essential Areas and
policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint
supportership of Eastern Virginia Medical School and Hampton University’s Skin of Color Research
Institute. Eastern Virginia School is accredited by the ACCME to provide continuing medical
education for physicians. Eastern Virginia Medical School designates this activity for a maximum of
11.5 AMA PRA Category 1 CreditsTM. Physicians should only claim credit commensurate with the
extent of their participation in the activity.
For more information on the meeting, visit www.huscri.org/symposium.
Dear Colleague,
You are invited to submit abstracts for the Skin of Color Symposium 2013.
The meeting will be held October 25-27, 2013 in Baltimore's charming and dynamic Inner Harbor at the Royal Sonesta Harbor Court Hotel.
Abstract submission opens July 1, 2013.
All abstracts MUST BE SUBMITTED ONLINE VIA THE
HUSCRI ABSTRACTS SUBMISSION SITE
(http://huscri.org/symposium/abstract-submission.php).
Important Notice
The following abstract submission policies will be firmly enforced:
No Previously Published Submissions
The abstract submitted must present original work that has not and will not be
published or presented prior to the 2013 HUSCRI meeting.
No Dual Submissions
The abstract must not have been submitted to any other upcoming meeting.
No Previously Presented Data
All abstracts must be new and original content OR include at least 50% new data if previously presented at a meeting.
For more information, visit www.huscri.org/symposium.
PASPCR
August 2013
14
PIGMENTATION COMMUNITY CONNECTIONS
Courtesy: http://www.mygeo.info/karten/802784.jpg
Patient/
ConsumerResearch
Industry Academia
Regulatory bodies
Medicine
Final products
In this issue, we continue the “Laboratory
Updates” with a column by Dr. Gisela Erf, the
“Industry Perspectives” with a column by Dr.
Gertrude-Emilia Costin, and the “Clinical
Insights” with a column by Dr. Reza Nejati. We
hope that you will be inspired to take the
opportunity to fill us in on what is happening in
your lab or company. Volunteers would be greatly
appreciated, just email us at
This initiative is part of our effort to keep the
Pigmentation community connected and to
emphasize the importance of collaboration and
communication between groups. We will keep
adding stars on our world map below each time
you contribute a column about your newest
research projects. So, let’s go on a global research
adventure!
PASPCR
August 2013
15
LABORATORY UPDATES
by Dr. Gisela Erf
The study of spontaneous autoimmune
vitiligo in the Smyth line (SL) chicken model
(Figure 1) has been part of my research program
for 24 years; initially in collaboration with Dr. J.
Robert Smyth, Jr. during my tenure as Assistant
Professor at Smith College, Northampton, MA
and, since 1994, as PI at the University of
Arkansas, Division of Agriculture, in
Fayetteville, AR. At the time I started working on
SL vitiligo, Dr. Smyth and collaborators already
had strong evidence of a role of the immune
system in the post-natal loss of SL melanocytes
(Smyth, 1989). Collectively, research in our avian
immunology laboratory established the
autoimmune nature of SL vitiligo and further
demonstrated the many biological and clinical
similarities between SL and human vitiligo (Erf
et al., 1995, 1997; Erf and Smyth, 1996; Shresta
et al., 1997; Wang and Erf, 2003, 2004; Wick et
al., 2006; Erf, 2010, 2013).
Like other autoimmune diseases, autoimmune
vitiligo in SL chickens is multifactorial in nature
requiring interplay of genetic, immune system
and environmental components for expression.
Genetic susceptibility to SL vitiligo appears to be
manifested in part by inherent defects or
“weaknesses” in the pigmentation system,
predisposing melanocytes to immunorecognition.
Additionally, genetic susceptibility may include
aberrant immunological activity at various levels.
Genetic susceptibility alone, however, does not
appear to be sufficient for SL vitiligo expression.
Rather, post-natal development of vitiligo in
susceptible SL chickens appears to be dependent
on environmental triggers. We identified routine
herpesvirus of turkey (HVT) administration (live
virus vaccination) at hatch as one environmental
factor that reliably triggers vitiligo expression in
susceptible SL chickens (Erf et al., 2001). With
live HVT administration at hatch, 80-95% of SL
hatch-mates will develop vitiligo between 6 and
20 weeks of age, whereas without HVT and in
defined housing conditions, the incidence of SL
vitiligo is reduced to nearly 10%. Lastly, as is the
case in human autoimmune vitiligo and other
autoimmune diseases, SLV can be accompanied
by other autoimmune/inflammatory diseases,
most notably autoimmune thyroiditis (Smyth,
1989).
Figure 1. Post-natal development of
autoimmune vitiligo in Smyth line chickens Top: One-day-old Smyth line chick (top left) and
6-week-old male and female Smyth line chickens
(right) prior to vitiligo onset.
Middle: Adolescent (12-week-old) SL chickens
with varying degrees of vitiligo (left); young
adult Smyth line hen without vitiligo (right).
Bottom: growing feathers with varying degrees of
pigmentation loss.
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Other characteristics of this animal model that
make it particularly suitable to study the etiology
and pathology of vitiligo is the location of, and
the continual access to, the autoimmune lesion. In
birds, melanocytes are present in the bottom 3-4
mm newest growth of growing feathers where
they are arranged around a column of inner pulp
(dermis-like tissue) within an epidermal layer of
keratinocytes. Growing feathers can be easily
removed for analysis from the same individual at
various times before and throughout development
and progression of SLV (Figure 1, bottom) and
the target tissue can be manipulated by
microinjection of test-materials (Erf et al., 1995,
Shi and Erf, 2012; Shi et al., 2012).
We currently maintain three lines of chickens
that constitute the model system for our research:
The Smyth line (SL), the Brown line (BL), and
the Light-brown Leghorn (LBL), all of which
have similar plumage pigmentation patterns and
are MHC-matched (B101/101
). As stated above,
under conventional rearing conditions, 80-95% of
SL chicks will develop vitiligo (SLV) between 6
and 20 weeks of age. Hence, SL chickens are
considered vitiligo susceptible with high vitiligo
expression. The BL is the parental line from
which the SL was originally derived (Smyth et
al., 1981; Smyth, 1989). While vitiligo
expression in the BL is rarely observed, BL
chickens are never-the-less considered vitiligo-
susceptible based on a 71% incidence of vitiligo
when treated with the DNA-methylation inhibitor
5-Aza-cytidine (Sreekumar et al., 1996). The
LBL chicken has no incidence of vitiligo and
does not develop vitiligo with 5-Aza-cytydine
treatment, hence the LBL line is considered
vitiligo resistant. Additionally, SL that carry a
sex-linked homozygous recessive dermal
pigmentation gene (id/id-male, id-female) that
results in grey/green pigmentation of the shanks
(SL-GS) generally do not express SL vitiligo.
With the complex, multifactorial nature of SL
autoimmune vitiligo, ongoing research in our
laboratory is also multifaceted. The genetic
susceptibility to SL vitiligo is being addressed
through two collaborations. Quantitative trait
analysis continues to be conducted by Drs. S.
Kerje and L. Andersson at Uppsala University in
Sweden. Whole genome sequencing comparing
SL, SL-GS, BL and LBL to the Red Jungle Fowl
reference chicken genome is being conducted by
my colleague Dr. B-W Kong, Department of
Poultry Science, University of Arkansas.
Preliminary findings based on genome re-
sequencing of SL and BL DNA revealed various
potential genetic markers with amino acid
changes and potential roles in vitiligo
development.
While examining in vitro and in vivo effects
of 4-TBP, a phenolic compound associated with
vitiligo development in humans, Ph.D. student
Lei Dong observed highly divergent responses of
SL melanocytes compared to SL-GS-, BL- and
LBL-control melanocytes. Aspects examined
included oxidative radical production,
pigmentation-, apoptosis- and stress-related gene-
expression, and melanocyte morphology.
Findings from this study not only demonstrated
altered ability of SL melanocytes to cope with
cellular stress, but also provided us with a system
to reveal “inherent weaknesses” in the
pigmentation system that may predispose SL
chickens to vitiligo development. We are in the
process of developing research collaborations
with Dr. Prashiela Manga’s research group at
New York University School of Medicine, New
York, NY, to further examine cellular responses
of avian and human melanocytes.
Making use of the opportunity to monitor the
developing autoimmune lesion, we continue to
investigate immune system activities leading to
autoimmune loss of melanocytes. Targeted and
global gene-expression analysis at the
transcriptome level throughout SL vitiligo
expression revealed a unique cytokine signature
with concomitant increases of IFN-γ, IL-10 and,
most prominently, IL-21 and IL-21receptor
expression (Shi and Erf, 2012; Shi et al., 2012).
Current research by Ph.D. students Kristen Byrne
and Daniel Falcon focus on identifying key
immunological components (innate and adaptive
immunity, respectively) and activities that drive
and mediate the loss of melanocytes in
susceptible SL chickens.
The environmental trigger of SLV expression
in the form of HVT continues to be another focus
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August 2013
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of our research group. Recently, we identified a
window in time when this virus can influence
SLV expression. Administration of HVT within
the first 2 weeks of life was found most effective
in triggering SLV expression. However, the
incidence of SLV dropped to 35% when HVT
was administered at 6 weeks. SLV did not
develop when HVT was administered at 10
weeks of age (the next time point tested) or later.
The observation of the age-dependent
ability/inability of HVT to trigger vitiligo
expression in susceptible SL chickens provides
unique opportunities to examine the interplay
between genetic susceptibility and environmental
triggers in autoimmune disease expression. We
are hoping to find collaborators who would be
interested in pursuing this important research
question.
Several studies are also underway by
undergraduate researchers in our laboratory.
Amir Mortazavi is examining qualitative and
quantitative aspects of melanocyte-specific
autoantibodies in a time course study starting
when the chicks were 2 weeks of age until SLV
had fully developed. Jordan Sorrick and Wilson
Huett are examining immune activities in the
choroids of SL with apparently normal sight,
partial blindness or complete blindness. Immune
system activities (cell infiltration, cytokine and
chemokine expression) associated with loss of
choroidal melanocytes and development of
blindness appear to be strikingly similar to
activities observed in the autoimmune lesion in
growing feathers.
We’ll continue to maintain this animal model
and to conduct research in this area; however,
with other commitments and limited funding,
research progress is slow and many aspects of
this project extend beyond our area of expertise.
Hopefully this update will initiate discussion on
collaborative studies and the valuable
contribution this avian model can make to our
understanding, prevention and treatment of
multifactorial, non-communicable diseases such
as autoimmune vitiligo.
References:
Wick, G., L. Andersson, K. Hala, M. E. Gershwin, C. F.
Selmi, G. F. Erf, S. J. Lamont, and R. Sgonc. 2006.
Avian models with spontaneous autoimmune diseases.
Adv. Immunol. 92:71-117.
Erf, G. F. 2010. Animal models. Pages 205-218 in: Vitiligo,
Picardo, M and A. Taieb, editors. Springer-Verlag
GmbH, Berlin Heidelberg, Germany.
Erf, G. F. 2013. Autoimmune diseases of poultry. Avian
Immunology, 2nd
edition. Davison F., Kaspers B., and
K. Schat, editors. Elsevier, Oxford, UK (in press)
Erf, G. F., and J. R. Smyth, Jr. 1996. Alterations in blood
leukocyte populations in Smyth Line chickens with
autoimmune vitiligo. Poult. Sci. 75:351-356.
Erf, G. F., A. V. Trejo-Skalli, and J. R. Smyth, Jr. 1995. T
cells in regenerating feathers of Smyth line chickens
with vitiligo. Clin. Immunol. Immunopathol. 76:120-
126.
Erf, G. F., A. V. Trejo-Skalli, M. Poulin, and J. R. Smyth,
Jr. 1997. Dermal lymphoid aggregates in autoimmune
Smyth line chickens. Vet. Immun. Immunopathol.
58:335-343.
Erf, G. F., T. K. Bersi, X. Wang, G. P. Sreekumar, and J. R.
Smyth, Jr. 2001. Herpesvirus connection in the
expression of autoimmune vitiligo in Smyth line
chickens. Pigment Cell Res. 14:40-46.
Shi, F., and G. F. Erf. 2012. IFN-gamma, IL-21 and IL-10
co-expression in evolving autoimmune vitiligo lesions
of Smyth line chickens. J. Invest. Dermatol. 132:642-
649.
Shi, F., B.-W. Kong, J. J. Song, J. Y. Lee, R. L.
Dienglewicz, and G. F. Erf. 2012. Understanding
mechanisms of spontaneous autoimmune vitiligo
development in the Smyth line chicken model by
transcriptomic microarray analysis of evolving lesions.
BMC Immunology 13:18; 1-15.
Shresta, S., J. R. Smyth, Jr., and G. F. Erf. 1997. Profiles of
pulp infiltrating lymphocytes at various times
throughout feather regeneration in Smyth line chickens
with vitiligo. Autoimmunity 25:193-201.
Smyth, J. R. Jr., R. E. Boissy, and K. V. Fite. 1981. The
DAM chicken: a model for spontaneous postnatal
cutaneous and ocular amelanosis. J. Hered. 72, 150-156.
Smyth, J.R. Jr. (1989). The Smyth chicken: a model for
autoimmune amelanosis. Poult. Biol. 2, 1-19.
Sreekumar, G. P., G. F. Erf, and J. R. Smyth, Jr. 1996. 5-
Azacytidine treatment induces autoimmune vitiligo in
the parental control strains of the Smyth line chicken
model for autoimmune vitiligo. Clin. Immunol.
Immunopathol. 81:136-144.
Wang, X., and G. F. Erf. 2003. Melanocyte-specific cell
mediated immune response in vitiliginous Smyth line
chickens. J. Autoimmun. 21:149-160.
Wang X., and G. F. Erf. 2004. Apoptosis in feathers of
Smyth line chickens with autoimmune vitiligo. J.
Autoimmun. 22: 21-30.
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August 2013
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Contact:
Gisela F. Erf, Ph.D. Tyson Professor in Avian Immunology
University of Arkansas
Center of Excellence for Poultry Science O-410
1260 W. Maple Street
Fayetteville, AR 72701, USA
Phone: (479-575-8664
Fax: 479-575-7139
Email: [email protected]
- // -
INDUSTRY PERSPECTIVES
by Dr. Gertrude-Emilia Costin
Colors and nuances of transitions in science.
How I remained faithful to the field of
pigmentation…
I was thinking the other day that our journey
in life (and our evolution in science as scientists)
is a series of transformations/transitions. Being a
biochemist by training, I was looking at my
“transitions” from the perspective of a molecule
that goes so often from its T (tense) state to the R
(relaxed) state based on numerous molecular
interactions that occur within the cellular
environment. Likewise, we are many times facing
numerous transitions and have to find our best
way to interact with others, with the fast-paced
changes in science and somehow, if possible,
remain close to a field if that is what makes us
comfortable and at ease as researchers. I realized
over the years that remaining faithful to the field
of pigmentation offered me the strength to
transition better when needed. Here is my journey
that I would like to share with you.
My first research project having to deal with
pigmentation started with my first job as assistant
researcher at the Institute of Biochemistry of the
Romanian Academy in Bucharest, Romania. One
of the ongoing projects in the Glycobiology
Laboratory led by the Director of the Institute,
Dr. Stefana Petrescu, investigated the folding and
maturation of tyrosinase, the enzyme that
regulates the melanin production in mammals.
One of the compounds used in their research was
the glycosylation inhibitor N-
butyldeoxynojirimycin (NB-DNJ). The studies of
the team led by Dr. Petrescu showed that this
small molecule interfered with the folding and
maturation of tyrosinase and completely
abolished the enzymatic activity of tyrosinase
resulting in the complete loss of melanin
production in B16F1 mouse melanoma cells (1).
While learning from my mentor, Dr. Mihaela
Trif, about intracellular trafficking using
liposomes I started to use those vehicles for a
more efficient way to transport NB-DNJ into
mouse melanoma cells (B16F1). Thus, my Ph.D.
project showed that pH-sensitive liposomes were
efficient carriers for the delivery of imino-sugars
such as NB-DNJ to the endoplasmic reticulum of
mammalian cells (2, 3). While the system based
on B16F1 cells was initially designed as a
working model for the later investigated
trafficking of hepatitis B (4, 5), I soon became
interested in gaining a better understanding of
how melanin production can be modulated in
various ways by agents that could eventually be
used in cosmetic formulations or drugs. Luckily,
the occasion arose when I had been offered the
opportunity to become part of Dr. Vincent
Hearing’s lab at National Institutes of Health
(NIH), in Bethesda, MD, USA. That was my first
transition as scientist.
In many ways, the skills acquired during my
Ph.D. training advanced while in Vince’s lab.
However, I felt farther apart from my original
basic training as biochemist and it looked like I
was more of a cellular and molecular biologist. It
was then when I felt that I transitioned slowly but
still kept alive my interest in skin color
modulation and the fascination with color in
general. While at NIH, I was involved in several
very interesting projects that fulfilled in some
ways my interest in modulation of melanin
production at the cellular and molecular level.
One of my projects investigated oculocutaneous
albinism type 4 (OCA4), a (then) newly
identified human autosomal recessive
hypopigmentary disorder of skin, hair, and eyes.
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Our data showed that tyrosinase was abnormally
secreted within immature melanosomes from
primary melanocytes I had derived from mice
that carry the underwhite (uw) mutation
(provided by Dr. Lynn Lamoreux, Texas A&M
University, College Station, TX, USA) which
affects the membrane-associated transporter
protein (MATP) (6).
A secondary project was based on
melanocytes that carry the slaty and slaty light
mutations in the gene for dopachrome
tautomerase (dct), an enzyme that is pivotal in
the biosynthesis of melanin and in the rapid
metabolism of its toxic intermediates. This
project actually started as a “hobby” as I tried to
improve my cell culture skills, knowing that these
melanocytes were more difficult to grow being
more sensitive due to their mutations. We
published a first set of results showing the culture
of immortalized lines (7) and then used them
further for a more ample project that showed that
the slaty and slaty light mutations affect the
eumelanin/pheomelanin synthesis but not the
intracellular trafficking of the mutant proteins (8).
While attending PanAmerican Society for
Pigment Cell Research (PASPCR) meetings I had
the opportunity to meet Dr. Gopinathan Menon
(currently at ISP Corporation) who introduced me
to Avon Products Global R&D (Suffern, NY,
USA) where I started to work in 2005 as senior
research scientist shortly after concluding my
post-doctoral training at NIH. I lived through that
transition with eyes wide open as the industry
language was much different from what I was
used to and as the interests of my group were skin
care at large and not exclusively focused only on
pigmentation. I admit that while I have learned a
lot about skin, skin care, consumer expectations
from cosmetic products in general, etc. I still
managed to use my pigmentation background
since melanin production is a special skin trait.
As you have already understood, that was my
second scientific transition. And it was the one
that brought me closer to answering the questions
I left Bucharest with years before: how can basic
knowledge be applied to create products that
modulate melanin production on the basis of the
novelty and efficacy of their ingredients? While
my tenure at Avon Products was unfortunately
relatively short, it stimulated me to publish a
successful review manuscript entitled “Human
skin pigmentation: melanocytes modulate skin
color in response to stress” and co-authored with
Vince Hearing (9). To my big surprise even to
this day, this review manuscript that compiled the
best of my knowledge in pigmentation at that
time is still ranking first among the most
frequently read papers after six years or more
after its publication in FASEB Journal (10).
Needless to say, I am very proud to have co-
authored a manuscript that is of such steady and
high interest in the field.
My third scientific transition took place in
2007 with the move to the Institute for In Vitro
Sciences, Inc. (IIVS) (Gaithersburg, MD, USA)
where I have worked as Study Director and
Toxicologist since. At first I felt uneasy to be
called a toxicologist as I have always been “a
biochemist in transition” and cellular/molecular
biologist at most. To this day I struggle with that
title as I came to realize that I have not followed
the classical training of a toxicologist in the
United States. I am rather a toxicologist by
training at work rather than in school. Which at
times can be an excellent route to gain
experience.
I have recently attended the introductory
lecture presented by Dr. Wallace Hayes as part of
the Toxicology for Industrial and Regulatory
Scientists Course organized by the American
College of Toxicology. The presenter asked the
audience to raise hands if any of us were
toxicologists. I believe it was the first time in the
last six years of working as a toxicologist when I
felt almost fully comfortable to claim that
position. And that is because I learned a lot and
came to realize that I do that every day
continuously, by reading, attending meetings,
conferences, discussing with our clients and
collaborators, etc. My happiness was cut short
soon thereafter while realizing during the course
that the general concept is that “the toxicologist”
is that scientist who has a wide background
pertaining to in vivo studies. That made me
realize that the in vitro toxicology field I’m in
right now is catching up but it also has a lot of
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20
convincing to do when it comes to replacing the
animal work with cell- or tissue-based assays.
And that is IIVS’s mission by promoting in vitro
assays as a replacement of animal
experimentation whenever possible, particularly
for the safety assessment of cosmetic and
personal care products and based on the strict
regulations currently enforced by the European
Union.
At IIVS I am the Study Director for a wide
array of in vitro assays focused on safety
assessment of various types of products
(cosmetic, household, pharmaceuticals,
pesticides, etc.). While my primary responsibility
is geared towards dermal safety, my knowledge
expanded quickly to assays using in vitro ocular,
mucosal testing platforms (11-13). IIVS has the
status of a Contract Research Organization
(CRO) and therefore the commercial studies
performed at IIVS came with the mandatory
training in Good Laboratory Practices (GLPs).
Well, that was scary at first as I was not familiar
with GLPs when I started but I can currently state
that acquiring this knowledge was a rewarding
and useful experience. I was supported by and
have benefited fully from the experience of all
my coworkers, especially our Vice-President,
Hans Raabe whom I report to, and our Quality
Assurance Unit (Amanda Ulrey and Teri Beth
Wallace).
While I very much enjoy the type of work I
am currently doing, this transition seemed to get
me even further away from the pigmentation
field. But I found my ways back to it… There
was still a wild card in my sleeve when it came to
keeping my “color interest” alive: during my
transfer from Avon to IIVS I got to share the
work on this newsletter that you are now reading
with Dr. Prashiela Manga, as we took over from
the previous editor, Dr. William (Bill) Oetting.
And that’s how you all got to interact with me in
one way or another and how, unaware and
unknowingly, helped me stay in touch with the
field. Many of you know the story of my journey
as the editor of the newsletter so I will not
elaborate on that part here. I will just say that it is
a very rewarding experience and that I am
thankful to all of you as members of PASPCR
and newsletters contributors. Working with
Prashiela over the last almost six years grew into
a nice friendship and in a flawless collaboration
with the same goal: keeping the membership
informed through the means of the newsletters.
Still, while the PASPCR Newsletters are my
main venue of keeping in touch with the
pigmentation community at large, I have to admit
that I continued my work at IIVS with R&D (14,
15) and commercial studies focusing on melanin
modulation. Furthermore, I benefit from yet
another fruitful collaboration and friendship with
Dr. Stanca Birlea (University of Colorado,
Denver, CO, USA) which started way back, in
2002 in Netherlands while attending the 18th
International Pigment Cell Conference (IPCC)
held in Egmond aan Zee. We published several
pigmentation manuscripts together since then and
she was the one who actually introduced me to
the clinical aspect of the field through studying
vitiligo and the mechanisms behind this skin
condition (16, 17). This is yet another very
rewarding relationship that keeps me close to the
news in pigmentation and that grew during all
these transitions I have shared with you in my
column.
My journey continues and I would like to stay
close to the pigmentation community like to my
first “scientific love”; although I feel often times
as a satellite by not being 100% emerged in the
field anymore, I found it fascinating and the
scientists are very friendly and sharing. Please
continue being as such as this makes our colorful
scientific community unique. Thank you!
References:
1. Petrescu, S. M., Petrescu, A. J., Titu, H. N., Dewk, R.
A., Platt, F. M. (1997). Inhibition of N-glycan
processing in B16 melanoma cells results in
inactivation of tyrosinase but does not prevent its
transport to melanosome. J. Biol. Chem. 272, 15796-
05803.
2. Costin, G. E., Trif, M., Nichita, N., Dwek, R. A.,
Petrescu, S. M. (2002). pH-sensitive liposomes are
efficient carrier for endoplasmic reticulum-targeted
drugs in mouse melanoma cells. Biochem. Biophys.
Res. Commun. 293, 918-923.
3. pH-sensitive liposomes for targeted drug delivery. WO
2003032946 A2. Available at:
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http://www.google.com/patents/WO2003032946A2?cl
=en.
4. Pollock, S., Antrobus, R., Newton, L., Kampa, B.,
Rossa, J., Latham, S., Nichita, N. B., Dwek, R. A.,
Zitzmann, N. (2010). Uptake and trafficking of
liposomes to the endoplasmic reticulum. FASEB J. 24,
1866-1878.
5. Liposome treatment of viral infections. WO
2008088581. Available at:
http://www.google.com/patents/WO2008088581A3?cl
=en.
6. Costin, G.-E., Valencia, J. C., Vieira, W. D.,
Lamoreux, L. M., Hearing, V. J. (2003). Tyrosinase
processing and intracellular trafficking is disrupted in
mouse primary melanocytes carrying the underwhite
(uw) mutation. A model for oculocutaneous albinism
(OCA) type 4. J. Cell. Sci. 116, 3203-3212.
7. Costin, G.-E., Vieira, W. D., Valencia, J. C., Rouzaud,
F., Lamoreux, M. L., Hearing, V. J. (2004).
Immortalization of mouse melanocytes carrying
mutations in various pigmentation genes. Anal.
Biochem. 335, 171-174.
8. Costin, G.-E., Valencia, J. C., Wakamatsu, K., Ito, S.,
Solano, F., Milac, A. L., Vieria, W. D., Yamaguchi,
Y., Rouzaud, F., Petrescu, A. J., Lamoreux, M. L.,
Hearing, V. J. (2005). Mutations in dopachrome
tautomeras (Dct) affect eumelanin/pheomelanin
synthesis, but do not affect intracellular trafficking of
the mutant protein. Biochem. J. 391, 249-259.
9. Costin, G.-E., Hearing, V. J. (2007). Human skin
pigmentation: melanocytes modulate skin color in
response to stress. FASEB J. 21, 976-994.
10. FASEB J. Most-Read Articles during June 2012 thru
May 2013 – updated monthly. (2013). Available at:
http://www.fasebj.org/reports/most-read. Accessed on
4 June 2013.
11. Costin, G.-E., Raabe, H., Curren, R. (2009). The in
vitro safety testing strategy for skin irritation using the
3D reconstructed human epidermis. Rom. J. Biochem.
46, 165-186.
12. Costin, G.-E., Raabe, H. A., Priston, R., Evans, E.,
Curren, R. D. (2011). Vaginal irritation models: the
current status of available alternative and in vitro tests.
Altern. Lab. Anim. 39, 317-337.
13. Costin, G.-E., Birlea, S. A., Norris, D. A. (2012).
Trends in wound repair: cellular and molecular basis of
regenerative therapy using electromagnetic fields.
Curr. Mol. Med. 12, 14-26.
14. Costin, G.-E., Raabe, H. (2013). Optimized in vitro
pigmentation screening assay using a reconstructed
three dimensional human skin model. Rom. J.
Biochem. 50, 15-27 (in press).
15. Costin, G.-E., Raabe, H. (2013). Technical challenges
associated with dosing devices used for topical
treatment of three dimensional reconstructed
pigmented tissues. Rom. J. Biochem. (in press).
16. Birlea, S. A., Costin, G.-E., Norris, D. A. (2008).
Cellular and molecular mechanisms involved in the
action of vitamin D analogs targeting vitiligo
depigmentation. Curr. Drug Targets 9, 345-359.
17. Birlea, S. A., Costin, G.-E., Norris, D. A. (2009). New
insights on therapy with vitamin D analogs targeting
the intracellular pathways that control repigmentation
in human vitiligo. Med. Res. Rev. 29, 514-546.
Contact:
Gertrude-Emilia Costin, Ph.D., M.B.A. Study Director
Editor - PanAmerican Society for Pigment
Cell Research (PASPCR) Newsletters
Institute for In Vitro Sciences, Inc.
30 W Watkins Mill Road #100
Gaithersburg, MD 20878, USA
Phone: 301-947-6524
Fax: 301-947-6538
E-mail: [email protected]
- // -
CLINICAL INSIGHTS
by Dr. Reza Nejati
Sensing the environment by skin
I am honored that Drs. Slominski and Costin
asked me to write the Clinical Insight column for
this number of the PASPCR Newsletter. As a
new member of the pigment cell research family,
I was unsure if I would have so much to say
compared to many experts in this field.
Nevertheless, I would like to share my
experiences in both clinical and research fields
which hopefully may inspire some young
researchers.
It seems like yesterday that I was an
energetic, curious boy growing up in a small city
in Iran. At age of 4 I saw a TV series on Louis
Pasteur’s life. His character, determination, and
perseverance impressed me profoundly, as did his
intellectual curiosity and desire for innovation.
Mistakenly assuming that he was a physician, I
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August 2013
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decided to follow in his footsteps by becoming a
doctor. It was my first dream of practicing
medicine, and research was an inseparable part of
it. While in medical school, pathology interested
me as it was the field that most closely resembled
my childhood notions about medicine.
Thoroughly hooked, I started my first pathology
residency upon graduation.
My first job after finishing residency was as
both a pathologist and Director of the Clinical
and Anatomical Laboratory of a state-run general
hospital. In addition to my hospital duties, I
established and ran a private clinical and
anatomical laboratory which was challenging
because I had to act as both a leader and a
technician. The lab worked at full capacity and
was expanding quickly. Everything looked
perfect until one night I asked myself a question:
“What had I done so far in my life?” I realized
that despite my enjoyment of clinical practice,
something seemed to be missing. It was the
scientific part of medicine which was my original
motivation for becoming a doctor. I remembered
Pasteur’s advice to young scientists at the
celebration of his 70th
birthday at Sorbonne:
[“Say to yourselves, first, “What have I done for
my instruction?” And as you gradually advance,
“What am I accomplishing?” Until the time
comes when you may have the immense
happiness of thinking that you have contributed
in some way to the welfare and progress of
mankind.”]
Thinking about a new pathology field where
advanced technologies, procedures and research
opportunities existed led me to come to the
United States and fulfilled my lifelong dream to
contribute to the scientific community. First, I
had the opportunity to work with Dr. Andre
Balla, Professor and Director of the Trans-
disciplinary Pathology Department at University
of Illinois at Chicago. I then went to Yale
University and had the great honor to work on
GYN and breast pathology services under the
leadership of Dr. Tavassoli. I worked at Yale
University till I joined the pathology residency
program at the University of Tennessee (UT).
Starting the second residency in pathology was
somehow different from the first one. It seems
like I have been given a second chance to
experience and see the whole story of my
professional life from the beginning to the end
and that I have the choice to do it in a different
way.
And so I started my residency. As time flies, I
first do my best to appreciate this chance and
enjoy every moment of my residency as well as
my time with my family. Secondly, bioscience
and molecular pathology are being merged in the
new pathology era, therefore we are in need of
more experts who have experience in both
clinical and bioscience fields. This expertise will
strengthen the bridge connecting research to
practice for the benefit of patients. Keeping these
two ideas in mind, I decided to choose a research
area during residency and start a basic research
project. At UT, I had the opportunity to attend
Dr. Slominski’s lectures and get firsthand
experience in his novel pigment cell research
projects. In particular, I was interested in his
lecture on the Regulation of cutaneous
hypothalamic-pituitary-adrenal (HPA) axis
homolog by ultraviolet light. To follow this
interest, I have juggled the busy residency life to
include work in Dr. Slominski’s lab on most
weekends.
The work on the HPA axis that I’ve been
doing has been fascinating. Historically,
proopiomelanocortin (POMC)-derived peptides
like α-MSH, ACTH and β-endorphin (β-END)
were the first stress-related mediators detected in
mammalian skin (Slominski et al., 1993). The
concept of the cutaneous establishment of a
peripheral hypothalamic-pituitary-adrenal (HPA)
axis equivalent defining as a cutaneous
equivalent of the HPA axis, became intuitive by
the discovery of corticotropin releasing hormone
(CRH) in skin and several other stress-related
factors, like Urocortin (UCN) (Slominski and
Mihm, 1996). These days, it is well documented
that mammalian skin expresses all functional
elements of HPA axis which influence local
homeostasis (reviewed in Slominski et al., 2007;
Skobowiat et al., 2011; Slominski et al., 2012).
The cutaneous HPA axis is not random but highly
organized and follows the central HPA axis
pattern, where CRH or UCN produced by skin
PASPCR
August 2013
23
cells and/or released by nerve endings interact
with CRH receptor type 1 (CRH-R1) to produce
POMC-derived β-END and ACTH, where the
latter stimulates the local production of cortisol
(COR) or corticosterone (CORT) (Ito et al., 2005;
Slominski et al., 2000; Slominski et al., 2005a;
Slominski et al., 2005b; Cirillo and Prime, 2011;
Hannen et al., 2011; Vukelic et al., 2011).
Cutaneous CRH, β-END, ACTH and
glucocorticoids (GCs) can regulate not only the
local (cutaneous) homeostasis, but also may
potentially affect central body homeostasis
influencing welfare, mood and food intake,
through the neural and vascular connections
(Slominski and Wortsman, 2000; Slominski et
al., 2000b; Slominski et al., 2012).
Since UVB is the major cutaneous stressor
and triggers the pigmentary and neuroendocrine
activities (Slominski et al., 2000; Slominski et al.,
2004; Slominski et al., 2012), we are currently
investigating its effects in mice (Skobowiat et al.,
submitted for publication). The preliminary data
of this study suggest that UVB may influence
elements of the HPA axis differently depending
on the genetic background and the animal
model(s). As our work continues, the animal
model(s) raise many other questions. Are the
genetic predetermined differences implicated in
the progression of skin tumors or pigmentary
disorders? Could any of the genetic differences
potentially be a predictor of therapy response?
Could elements of the cutaneous HPA axis be
used as targets for therapy or immunoresponse?
Can we use any of these as markers of survival
and metastasis? We hope that our future studies
open a new window to the mysterious world of
pigment cell disorders.
References:
Slominski A, Paus R, Wortsman J. On the potential role of
proopiomelanocortin in skin physiology and pathology.
Mol. Cell. Endocrinol 1993;93:C1-6.
Slominski A, Mihm M. Potential mechanism of skin
response to stress. Int. J. Dermatol 1996;35:849-851.
Slominski, A., Wortsman, J., Tuckey, R.C. and Paus, R.
Differential expression of HPA axis homolog in the
skin. Mol Cell Endocrinol 2007;265-266:143-149.
Skobowiat C, Dowdy JC, Sayre RM, Tuckey RC,
Slominski A. Cutaneous hypothalamic-pituitary-
adrenal axis homolog: regulation by ultraviolet
radiation. Am J Physiol Endocrinol Metab.
2011;301(3):E484-93.
Slominski, A.T., Zmijewski, M.A., Skobowiat, C., Zbytek,
B., Slominski, R.M. and Steketee, J.D. Sensing the
environment: regulation of local and global
homeostasis by the skin's neuroendocrine system. Adv
Anat Embryol Cell Biol 2012;212:1-115.
Ito, N., Ito, T., Kromminga, A., Bettermann, A., Takigawa,
M., Kees, F., Straub, R.H. and Paus, R. Human hair
follicles display a functional equivalent of the
hypothalamic-pituitary-adrenal axis and synthesize
cortisol. FASEB J 2005;19:1332-4.
Slominski, A., Zbytek, B., Semak, I., Sweatman, T. and
Wortsman, J., CRH stimulates POMC activity and
corticosterone production in dermal fibroblasts. J
Neuroimmunol 2005a;162:97-102.
Slominski, A., Zbytek, B., Szczesniewski, A., Semak, I.,
Kaminski, J., Sweatman, T. and Wortsman, J. CRH
stimulation of corticosteroids production in
melanocytes is mediated by ACTH. Am J Physiol
Endocrinol Metab 2005b;288:E701-6.
Cirillo, N. and Prime, S.S. Keratinocytes synthesize and
activate cortisol. J Cell Biochem 2011;112:1499-505.
Hannen, R.F., Michael, A.E., Jaulim, A., Bhogal, R.,
Burrin, J.M. and Philpott, M.P. Steroid synthesis by
primary human keratinocytes; implications for skin
disease. Biochem Biophys Res Commun 2011;404:62-
7.
Vukelic, S., Stojadinovic, O., Pastar, I., Rabach, M.,
Krzyzanowska, A., Lebrun, E., Davis, S.C., Resnik, S.,
Brem, H. and Tomic-Canic, M., Cortisol synthesis in
epidermis is induced by IL-1 and tissue injury. J Biol
Chem 2011;286:10265-75.
Slominski, A. and Wortsman, J. Neuroendocrinology of the
skin. Endocr Rev 2000;21:457-87.
Slominski, A., Wortsman, J., Luger, T., Paus, R. and
Solomon, S. Corticotropin releasing hormone and
proopiomelanocortin involvement in the cutaneous
response to stress. Physiol Rev 2000;80:979-1020.
Slominski, A., Tobin, D.J., Shibahara, S. and Wortsman, J.,
2004. Melanin pigmentation in mammalian skin and its
hormonal regulation. Physiol Rev 2004;84:1155-1228.
Contact:
Reza Nejati, M.D.
University of Tennessee Health Science Center
Department of Pathology & Laboratory Medicine
930 Madison 5th
floor
Memphis, TN 38103, USA
E-mail: [email protected]
PASPCR
August 2013
24
MEMBERS IN THE NEWS
Yale News (Yale University) recently featured one
of the recent studies performed in collaboration by
Yale University, University of Colorado and
Denver Police Department Crime lab and authored
by several PASPCR members. The study was
published in PLOS one and is entitled “A
melanoma brain metastasis with a donor-patient
hybrid genome following bone marrow
transplantation: first evidence for fusion in human
cancer” by R. Lazova, G. S. Laberge, E. Duvall, N.
Spoelstra, V. Klump, M. Sznol, D. Cooper, R. A.
Spritz, J. T. Chang and J. M. Pawelek.
Visit http://news.yale.edu/2013/06/26/how-
cancer-spreads-metastatic-tumor-hybrid-cancer-
cell-and-white-blood-cell to read the press release
by Yale University and to get direct access to the
original paper.
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POSITIONS WANTED/AVAILABLE
Postings for Positions Wanted will be open only
to members of the PanAmerican Society for
Pigment Cell Research (PASPCR) or its sister
Societies (ASPCR, JSPCR and ESPCR). Postings
for Positions Available will be open to all
individuals and institutions so long as the position
is related to pigment cell research. Please send
postings to [email protected].
The postings will remain on the Positions
Wanted and Available section of the PASPCR
Newsletter and on the web page for 1 year, unless
other arrangements are made. Please provide an
expiration date for any submitted posting if less
than 1 year. Final decisions will be made by the
Publications Committee of the PASPCR.
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