The Oregon Health &Science University (OHSU) Department of Dermatology proposes continuation of its "Training in the Molecular Basis of Skin Pathobiology" program with objectives to train highly qualified predoctoral and postdoctoral researchers for academic careers in experimental dermatology and related epithelial disorders, in particular cancer and inflammatory disease. Specifically we aim: 1. to engage trainees in furthering an understanding of the molecular pathways that underlie mucosal and skin disease, in evolving and using specialized approaches needed to advance the field, and in providing insight and ultimately application to clinical problems;and 2, to foster interactions among our mentor/trainee laboratories that enrich the dermatology field and increase its scope and impact on understanding and treating disease. The proposed program offers a core of mentors including internationally recognized faculty researchers from the Dermatology research division and 5 basic science departments who through this program interact and collaborate to form a focus on epithelial carcinogenesis and inflammatory disease. The training program is designed to achieve these aims by 1) engaging trainees and mentors in discussion, interaction/collaboration and sharing ideas and approaches in multiple areas of epithelial carcinogenesis and inflammatory disease of surface epithelia (facilitated through monthly rotation of trainee presentations of data attended by all trainees and mentors, co-mentoring, and sharing specialized resources) and 2) exposing trainees to translation of basic science to clinical treatment through close interaction with clinical dermatologists and oncologists (facilitated through our monthly translational topics forum and journal clubs with joint presentations of residents and scientists). This program spans skin and mucosal carcinogenesis, homeostatic, oncogenic and tumor suppressor mechanisms (Trim32, Wnt, TGF?1/SMAD, c-Myc, Ras and B-Raf, insulin-like growth factors, Cox2, Piasy, p73, inhibitory SMADs), and cytokines in cancer and inflammatory disorders, and fosters sharing of specialized research resources for use in trainee projects (epithelial-targeted gene-switch models of skin, colon, and head and neck cancer and inflammatory disease;non-invasive optical imaging;specialized cell isolation of epithelial and immune populations;and our Molecular Profiling Resource containing freshly cryopreserved human tumor specimens and normal mucosa and skin controls). Two predoctoral and three postdoctoral MD, PhD or MD/PhD candidates are appointed each year, selected for their aptitude, the special experience they bring to the field and their desire to carry out skin/mucosa research with a strong clinical translational component and potential for impact on investigative dermatology in the areas of cancer and inflammation.

Public Health Relevance

This program studies cancer and inflammatory diseases of surface organs of the body (skin, oral and intestinal mucosa), to understand how they are caused at the tissue, cellular, molecular and biochemical levels, and to discover new treatments. Skin is a good model because we can see cancer and inflammatory diseases develop from their earliest stages and easily see responses to new treatments;however our group is developing non-invasive imaging that allows us to see oral and intestinal disease as well and to connect the pathology with changes in adult stem cells, cancer gene expression and inflammation-promoting molecules at these organ sites. Cancers of these and related epithelia make up the majority of human cancers, the most deadly of these affecting over 680,000 people a year in the US, with nearly 300,000 deaths, while psoriasis alone (a skin inflammatory disease) affects ~ 7.5 million people in the US annually,

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Institutional National Research Service Award (T32)
Project #
5T32CA106195-09
Application #
8318775
Study Section
Subcommittee G - Education (NCI)
Program Officer
Damico, Mark W
Project Start
2004-06-01
Project End
2014-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
9
Fiscal Year
2012
Total Cost
$258,323
Indirect Cost
$16,685
Name
Oregon Health and Science University
Department
Dermatology
Type
Schools of Medicine
DUNS #
096997515
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

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