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 #
5T32CA106195-10
Application #
8531667
Study Section
Subcommittee G - Education (NCI)
Program Officer
Damico, Mark W
Project Start
2004-06-01
Project End
2014-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
10
Fiscal Year
2013
Total Cost
$259,515
Indirect Cost
$16,853
Name
Oregon Health and Science University
Department
Dermatology
Type
Schools of Medicine
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239
Lane, Ryan S; Femel, Julia; Breazeale, Alec P et al. (2018) IFN?-activated dermal lymphatic vessels inhibit cytotoxic T cells in melanoma and inflamed skin. J Exp Med 215:3057-3074
Smith, Nicholas R; Swain, John R; Davies, Paige S et al. (2018) Monoclonal Antibodies Reveal Dynamic Plasticity Between Lgr5- and Bmi1-Expressing Intestinal Cell Populations. Cell Mol Gastroenterol Hepatol 6:79-96
Sha, Yan; Vartanian, Vladimir; Owen, Nichole et al. (2018) Modulation of UVB-induced Carcinogenesis by Activation of Alternative DNA Repair Pathways. Sci Rep 8:705
Paterson, Elyse K; Courtneidge, Sara A (2018) Invadosomes are coming: new insights into function and disease relevance. FEBS J 285:8-27
Medler, Terry R; Murugan, Dhaarini; Horton, Wesley et al. (2018) Complement C5a Fosters Squamous Carcinogenesis and Limits T Cell Response to Chemotherapy. Cancer Cell 34:561-578.e6
Lane, Ryan S; Lund, Amanda W (2018) Non-hematopoietic Control of Peripheral Tissue T Cell Responses: Implications for Solid Tumors. Front Immunol 9:2662
Gast, Charles E; Silk, Alain D; Zarour, Luai et al. (2018) Cell fusion potentiates tumor heterogeneity and reveals circulating hybrid cells that correlate with stage and survival. Sci Adv 4:eaat7828
Huang, Tao; Phelps, Carey; Wang, Jing et al. (2018) Simultaneous Multicolor Single-Molecule Tracking with Single-Laser Excitation via Spectral Imaging. Biophys J 114:301-310
Sha, Yan; Minko, Irina G; Malik, Chanchal K et al. (2017) Error-prone replication bypass of the imidazole ring-opened formamidopyrimidine deoxyguanosine adduct. Environ Mol Mutagen 58:182-189
Minko, Irina G; Rizzo, Carmelo J; Lloyd, R Stephen (2017) Mutagenic potential of nitrogen mustard-induced formamidopyrimidine DNA adduct: Contribution of the non-canonical ?-anomer. J Biol Chem 292:18790-18799

Showing the most recent 10 out of 80 publications