The OHSU Dermatology Research Division merges basic, clinical and translational research in skin/mucosal cancers and other dermatologic diseases. We build upon three elements:
- Molecular, cellular and tissue based models of disease
- Specialized cell separation and culture
- Molecular genetics for diagnosis and therapy
The research division is designed to foster interactions among basic and clinical scientists and resident fellows of the department for novel and synergistic research activities and applications.
Basic science labs
Molly Kulesz-Martin, Ph.D., Professor Emeritus
The Kulesz-Martin Lab research springs from the OHSU-bred paradigm that cancer causes make the best targets for prevention and therapy. Human surface epithelial cells of the skin and mucosal linings of the oral cavity, nose and throat can accumulate mutations that alter cellular lifespan, impair function and impact genomic stability leading to fields of cells already initiated on the road to cancer. Skin cancers and head and neck mucosal cancers arise in these fields, and, because of their accessible location, provide a unique window into the multiple stages of cancer through its earliest development. Previous research in my lab led to the development of one of the few clonal models of normal, initiated, benign, and malignant and metastatic cells, useful for uncovering mechanisms of stage-specific tumor initiation and progression, and to the identification and functional characterization of naturally occurring alternative splice variants of the tumor suppressors p53 and p73.
These form the background for three complementary areas of genomic and functional research on patient-derived cells in our laboratory, with our bioinformatics collaborators, which are:
- Defining targetable pathways in individual patient-derived oral and skin cancers, including those impacted by inflammation
- Determining a high risk signature of mutation and gene expression that predicts recurrence, deep invasion and metastasis and drug sensitivities, that can be developed into a clinical test of skin and mucosal cancers that will guide patient monitoring and treatment
- Validating targets for prevention and therapy in patient tumor cell-derived preclinical models to expand options for effective, minimally toxic therapy tailored to each patient.
Rajan Kulkarni, M.D., Ph.D., Associate Professor of Dermatology
Hilary Seifert, Ph.D., Research Instructor
Terri Clister, Ph.D., Senior Research Associate
Matthew Chang, Computation Biology Intern
Reilly Fankhauser, Research Assistant 2
Rachel Berryman, Research Assistant 2
Peter Pham, Research Assistant 2
Zach Garrison, Research Assistant 2
The Kulkarni Lab focuses on the intersection of basic biology, technology and medicine to help better realize the vision of personalized medicine in cancer.
Kulkarni Lab research is now centered on basic and translational studies to enable molecularly-based, personalized approaches to cancer care, in collaboration with the VA, the Center for Early Detection Research (CEDAR), and the Knight Cancer Institute. To this end, we are collaborating extensively with technology groups at OHSU and CEDAR to improve our abilities to gain information about tumor heterogeneity through single cell isolation and analysis, for all cancers, but primarily in melanoma, prostate and lung cancers.
A parallel line of research focuses on oncodermatology and elucidating the mechanisms by which novel chemotherapeutics and immunotherapies cause skin toxicities/rashes and whether these mechanisms have any correlation with anti-tumor effect and overall outcome. Our overall goal is to couple genomic, epigenetic and clinical information to design novel treatment strategies and ultimately improve patient outcomes.
Dr. Kulkarni's past research focused on two main areas:
- Development of innovative methods to enable earlier cancer detection and its recurrence through isolation and analysis of circulating tumor cells
- Improving our understanding of 3D tumor architecture through tissue clearing methods (PARS and PACT CLARITY) for intact 3D tissue imaging.
Sancy Leachman, M.D., Ph.D., Professor and Chair, Dermatology; Director, Melanoma Research Program, Knight Cancer Institute
Pamela Cassidy, Ph.D., Research Associate Professor
Gail Kent, Research Associate
The Leachman-Cassidy Lab is a transdisciplinary and translational research team designed to improve melanoma health outcomes with a focus on melanoma prevention and early detection before metastasis can occur. Their goal is to eliminate as many melanoma-related deaths as possible utilizing a full-spectrum approach; from bench-side basic science, to bed-side treatment and care, to wide-scale public health outreach.
Dr. Cassidy leads the Lab's translational and basic science efforts, incorporating molecular, cellular and human genetics studies to understand and develop prevention agents for the highest risk individuals. Together they have a long standing program in collaboration with Dr. Elizabeth Berry, to understand and identify individuals who are genetically predisposed to melanoma, for the purpose of improved screening and detection and chemoprevention.
Dr. Leachman leads the clinical science and population health efforts through her nationwide War on MelanomaTM effort. This includes the creation of the largest melanoma registry in the country, as well as other key efforts such as the MoleMapperTM mole tracking phone app, melanoma education efforts for several key audiences, and the public health campaign Start Seeing MelanomaTM. She is also an advocate for innovative technologies for melanoma screening and diagnosis.
Yuangang Liu, Ph.D., Research Assistant Professor
Zhiping Wang, Ph.D., Senior Research Associate
Liu Lab's research interest is to understand the molecular basis of skin interaction with the environment. As the first line of defense, innate immunity plays a central role in skin homeostasis. Altered innate immunity contributes to the pathogenesis of many inflammatory skin diseases, including atopic dermatitis (AD), psoriasis, and cancer. Research has been focused on understanding the role of TRIM32 in AD, psoriasis, and cancer. TRIM32 is an E3 ubiquitin ligase with innate antiviral activity. We found that TRIM32 is overexpressed in psoriasis and downregulated in atopic dermatitis. Liu Lab seeks to define the role of TRIM32 and its downstream targets in innate immunity in order to:
- address the questions why AD patients are susceptible to viral infection and Th2 polarized in response to infection
- harness innate immune pathway in cancer therapy
Lisa M. Coussens, Ph.D.
Professor of Cell, Developmental and Cancer Biology, School of Medicine
Associate Director for Basic Research, OHSU Knight Cancer Institute, School of Medicine
Chair, Department of Cell, Developmental & Cancer Biology
Cell and Developmental Biology Graduate Program, School of Medicine
Cancer Biology Graduate Program, School of Medicine
Program in Molecular and Cellular Biosciences, School of Medicine
The Ruhland lab is broadly interested in understanding the who, what, when and where of antigen presentation in the lymph node. In particular we focus on the pathways used by myeloid cell populations to bring tumor-derived antigen into the lymph node and subsequently seed antigen into lymph node resident cell populations.
Piperine for the treatment of vitiligo
Vitiligo, a skin pigmentation disorder which afflicts an estimated 100 million people worldwide, is characterized by the loss of pigment in affected areas of skin. It is neither life threatening nor contagious, but the white skin patches it causes produce emotional distress for many, and often lead to social ostracism because of a widespread misconception that the condition is infectious.
An estimated one to two percent of the world’s population, or 60 to 100 million people, suffer from the malady. Current treatments, which rely on immunosuppression or ultraviolet radiation to stimulate repigmentation, take time to work and are only partially effective, often producing a mottled appearance. Excessive UV radiation also poses the risk of skin cancer.
The Department of Dermatology has supported scientific research by Amala Soumyanath, Ph.D., a professor in the Department of Neurology, and Philippe Thuillier, Ph.D., an assistant professor in the Department of Dermatology, for their promising work on a new potential vitiligo therapy. Piperine, an extract of black pepper, has been demonstrated to enhance melanocyte growth in vivo. The goal of this innovative research is to offer people with vitiligo a new and effective treatment option.
“Based on the animal studies we have done, piperine, if proven safe in humans, may provide a means of speeding up repigmentation produced by standard treatments such as narrow band UVB” said Amala Soumyanath, Ph.D. “Vitiligo is a highly visible disease that can greatly affect patients psychologically and emotionally, even driving some to consider suicide. Any breakthrough in treating it would benefit a huge number of people around the world.”
Soumyanath and her collaborators have reported on the effects of their compounds in animals in a paper published in the British Journal of Dermatology. But development of the concept dates back more than two decades to work initiated by Soumyanath at King’s College London. Soumyanath’s group discovered –while researching natural remedies for vitiligo – that piperine, the pungent component of black pepper, stimulated the proliferation of melanocytes in cell cultures. Melanocytes are the cells that produce pigmentation in the skin. The researchers then designed and tested many synthetic piperine analogs and identified a number that produced the same result.
The group subsequently found that piperine and two of its analogs – tetrahydropiperine (THP) and a cyclohexyl derivative (RCHP) produced light, even pigmentation when applied to the skin of a poorly pigmented mouse model. When combined with UV radiation, the skin grew significantly darker and showed none of the patchiness caused by UV treatment alone. Moreover, skin pre-treated with a piperine compound required fewer UV exposures, thus lowering the cancer risk, and it took longer for the pigmentation to fade again than when UV alone was used.
Soumyanath came to OHSU in 2003, where she has established collaborations with scientific and clinical researchers at the Department of Dermatology to continue work on this project, including Philippe Thuillier, Ph.D., (Assistant Professor), Dr Pamela Cassidy Ph.D (Professor), Dr Eric Simpson (Professor) and Dr Sancy Leachman M.D. PhD (Professor and Chair of Dermatology). “Dr. Soumyanath’s discoveries open up completely new and exciting treatment possibilities for those individuals affected by vitiligo,” said Dr Sancy Leachman, M.D., Ph.D. “There is a huge unmet need for this disease, since we have very few treatments to offer patients right now,” she noted.
Soumyanath and the collaborative team are continuing to find additional scientific answers. An important step before clinical trials can be undertaken in the U.S., said Soumyanath, is to determine whether the repigmentation effects of piperine is associated in any way with melanoma or other skin cancers. “From our mouse and cell studies so far, it doesn’t appear that is the case,” she said. “In fact, piperine seems to have anti-cancer or cancer preventive effects. We are hopeful that more detailed research will bear this out.” The group has developed a cream formulation that allows good penetration of piperine into the skin. They are eager to test piperine in volunteers with vitiligo once they are able secure funding for a clinical trial.’
OHSU acquired the patents to Soumyanath’s piperine compounds from King’s College London and BTG International Ltd. in 2006, and is actively seeking a commercial partner to advance piperine through pharmaceutical development. In the meantime, the researchers are actively seeking grants and philanthropic donations to obtain data to attract such a partner.
To support this effort financially, you can choose Vitiligo Research on our Foundation Giving page.