The OHSU Department of Dermatology proposes continuation of its 10-year "Training in the Molecular Basis of Skin/Mucosa Pathobiology" program, with the objective of preparing highly qualified pre-doctoral and postdoctoral researchers for academic careers that lead to better understanding and treatment of skin, oral and intestinal cancers. Currently the only NCI-funded training program at OHSU, our program focuses on cancers that are accessible from their earliest stages, and thus ideal for understanding multi-step carcinogenesis, testing prevention strategies, and targeting and monitoring success of treatments. Specifically, we aim: 1. to engage trainees in furthering an understanding of the molecular pathways that underlie skin/mucosa disease, in evolving and using specialized approaches to advance the field, and in providing insight and ultimately applications to clinical problems~ and 2. to foster interactions among mentor/trainee laboratories that enrich the dermatology field and increase its scope and impact on understanding and treating cancer and inflammatory disease. The program offers internationally recognized faculty researchers from dermatology, 6 basic science departments and 5 OHSU institutes and centers, who are dedicated to training the next generation and collaborating to form a focus on carcinogenesis, diagnostics, prevention and treatment of cancer and inflammatory disease. The program engages trainees and mentors in sharing of ideas and specialized resources (keratinocyte- and melanocyte-targeted inducible genetic models of skin, colon and head and neck cancer and inflammatory disease~ non-invasive optical imaging~ specialized cell isolation of epithelial and immun populations~ the Molecular Profiling Resource containing freshly cryopreserved human tumor and normal mucosa and skin specimens and primary skin and oral tumor cultures), and exposes trainees to translation of basic science to clinical treatment through program-specific curriculum. These include monthly Joint Lab meeting for research presentations by trainees and dermatology research laboratories as well as outside speakers selected by trainees~ the forums "Translational Topics" and High Impact Translational (HIT) journal club that feature joint presentations of residents and scientists~ mandatory advisory committee meetings~ and didactic, career development and responsible conduct of research training. The scientific scope includes homeostatic and oncogenic mechanisms (c-Myc, Ras and B-Raf, IGFs, Trim32, Wnt, EGFR, RXR, CTIP, CDKN2A/p16, MC1R, cytokines and their receptors) of tumor, endothelial, immune and other stromal cell cross talk and role of matrix and secreted factors. Two predoctoral and 3 postdoctoral MD, PhD or MD/PhD candidates are appointed each year, selected for aptitude, special experience to offer the field, desire to incorporate a strong translational component and potential for impact on investigative dermatology in skin/mucosa cancer and inflammation.

Public Health Relevance

This program trains the next generation of scientists and physicians in cancer and inflammatory diseases of surface organs of the body (skin, oral and intestinal mucosa), so that they can to contribute to understanding causes at the tissue, cellular, molecular and biochemical levels and discovering new treatments. In these organs we can see cancer and inflammatory diseases develop from their earliest stages and easily observe responses to treatments, not only with the naked eye but also with non-invasive and advanced imaging being developed in our program to connect visible pathology with the underlying changes in cells, cancer gene expression, and inflammation-promoting molecules. Studies of skin and mucosa can offer broader insights about epithelial cancers (that make up the majority of human cancers, including many of its most deadly) and about regulatory mechanisms in non-cancerous skin inflammatory diseases like psoriasis, that alone affects ~7.5 million people in the U.S. annually.

Agency
National Institute of Health (NIH)
Type
Institutional National Research Service Award (T32)
Project #
2T32CA106195-11
Application #
8667277
Study Section
Special Emphasis Panel (ZCA1)
Program Officer
Damico, Mark W
Project Start
Project End
Budget Start
Budget End
Support Year
11
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Oregon Health and Science University
Department
Dermatology
Type
Schools of Medicine
DUNS #
City
Portland
State
OR
Country
United States
Zip Code
97239
Affara, Nesrine I; Ruffell, Brian; Medler, Terry R et al. (2014) B cells regulate macrophage phenotype and response to chemotherapy in squamous carcinomas. Cancer Cell 25:809-21
Medler, Terry R; Coussens, Lisa M (2014) Duality of the immune response in cancer: lessons learned from skin. J Invest Dermatol 134:E23-8
Coleman, Daniel J; Garcia, Gloria; Hyter, Stephen et al. (2014) Retinoid-X-receptors (?/?) in melanocytes modulate innate immune responses and differentially regulate cell survival following UV irradiation. PLoS Genet 10:e1004321
Farrell, Amy S; Pelz, Carl; Wang, Xiaoyan et al. (2013) Pin1 regulates the dynamics of c-Myc DNA binding to facilitate target gene regulation and oncogenesis. Mol Cell Biol 33:2930-49
Tormoen, Garth W; Khader, Ayesha; Gruber, Andras et al. (2013) Physiological levels of blood coagulation factors IX and X control coagulation kinetics in an in vitro model of circulating tissue factor. Phys Biol 10:036003
Kulesz-Martin, Molly F; Lagowski, James; Olson, Susan et al. (2013) A molecular case report: functional assay of tyrosine kinase inhibitors in cells from a patient's primary renal cell carcinoma. Cancer Biol Ther 14:95-9
Hyter, Stephen; Coleman, Daniel J; Ganguli-Indra, Gitali et al. (2013) Endothelin-1 is a transcriptional target of p53 in epidermal keratinocytes and regulates ultraviolet-induced melanocyte homeostasis. Pigment Cell Melanoma Res 26:247-58
Silk, Alain D; Gast, Charles E; Davies, Paige S et al. (2013) Fusion between hematopoietic and epithelial cells in adult human intestine. PLoS One 8:e55572
Malkoski, Stephen P; Haeger, Sarah M; Cleaver, Timothy G et al. (2012) Loss of transforming growth factor beta type II receptor increases aggressive tumor behavior and reduces survival in lung adenocarcinoma and squamous cell carcinoma. Clin Cancer Res 18:2173-83
Rizzo, Heather L; Kagami, Shinji; Phillips, Kevin G et al. (2011) IL-23-mediated psoriasis-like epidermal hyperplasia is dependent on IL-17A. J Immunol 186:1495-502

Showing the most recent 10 out of 30 publications