A Center of Research Translation in Psoriasis based at University Hospitals Case Medical Center will integrate a strong psoriasis and skin disease research base with a large existing cohort of psoriasis patients. $5M from the new University Hospitals Murdough Family Center for Psoriasis will further increase the capabilities and geography of the clinical referral network, and in combination with $2M from Case School of Medicine for recruitment in psoriasis, these resources comprise a substantial institutional commitment to the CORT. The Skin Diseases Research Center's cutaneous biology infrastructure and experience will accelerate the Case Psoriasis CORT's advances for psoriasis patient benefit. The translational projects envisioned will test innovative therapeutic interventions in psoriasis that are based upon new mechanistic findings. They also provide new pathogenetic information using biologic samples from patients and animal models. It is intended that each Project will generate therapeutic modalities that change the treatment of psoriasis patients. Project 1 is a novel photodynamic therapy (PDT) Phase I mechanistic, safety, and preliminary efficacy study which also develops a real-time patient-optimized therapy device. Project 2 is a basic study that determines novel roles for S100 proteins in the pathogenesis of psoriasis, including proof-of-principle testing of S100 and macrophage interplay in psoriasis skin on xenogenic transplants. Project 3 takes advantage of a novel transgenic mouse model of psoriasiform dermatitis to examine the potential role of VEGF, S100 A8/9 and vascular changes exacerbating psoriasis. Project 4 explores whether the new clinical finding that psoriasis patients are at higher cardiovascular risk is related to S100 A8/9 overexpression and addresses if aggressive psoriasis treatment directed at S100 serum levels improves cardiovascular risk. The studies will be supported by two project-focused scientific Cores in A) Statistics and B) Systems Biology, and by an Administrative Core. An Advisory Board with representation by both male and female patients, as well as parents, some of whom are also renowned scientists, will oversee the CORT and the P&F review. The CORT will thus bring a multidisciplinary team of translational physician scientists, nurses, community clinicians, laity, and basic scientists from different departments and disciplines together to apply the intellectual and scientific resources of the institution to new therapies for psoriasis patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Specialized Center (P50)
Project #
5P50AR055508-05
Application #
8126343
Study Section
Special Emphasis Panel (ZAR1-MLB-G (O1))
Program Officer
Cibotti, Ricardo
Project Start
2007-09-24
Project End
2013-08-31
Budget Start
2011-09-01
Budget End
2013-08-31
Support Year
5
Fiscal Year
2011
Total Cost
$784,722
Indirect Cost
Name
Case Western Reserve University
Department
Dermatology
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
Arbiser, Jack L; Nowak, Ron; Michaels, Kellie et al. (2017) Evidence for biochemical barrier restoration: Topical solenopsin analogs improve inflammation and acanthosis in the KC-Tie2 mouse model of psoriasis. Sci Rep 7:11198
Swindell, William R; Michaels, Kellie A; Sutter, Andrew J et al. (2017) Imiquimod has strain-dependent effects in mice and does not uniquely model human psoriasis. Genome Med 9:24
Hawkes, Jason E; Gudjonsson, Johann E; Ward, Nicole L (2017) The Snowballing Literature on Imiquimod-Induced Skin Inflammation in Mice: A Critical Appraisal. J Invest Dermatol 137:546-549
Santilli, S; Kast, D R; Grozdev, I et al. (2016) Visualization of atherosclerosis as detected by coronary artery calcium and carotid intima-media thickness reveals significant atherosclerosis in a cross-sectional study of psoriasis patients in a tertiary care center. J Transl Med 14:217
Soler, David C; Ohtola, Jennifer; Sugiyama, Hideaki et al. (2016) Activated T cells exhibit increased uptake of silicon phthalocyanine Pc 4 and increased susceptibility to Pc 4-photodynamic therapy-mediated cell death. Photochem Photobiol Sci 15:822-31
Wang, Yunmei; Golden, Jackelyn B; Fritz, Yi et al. (2016) Interleukin 6 regulates psoriasiform inflammation-associated thrombosis. JCI Insight 1:e89384
Golden, Jackelyn B; Groft, Sarah G; Squeri, Michael V et al. (2015) Chronic Psoriatic Skin Inflammation Leads to Increased Monocyte Adhesion and Aggregation. J Immunol 195:2006-18
Ward, Nicole L; Bhagathavula, Narasimharao; Johnston, Andrew et al. (2015) Erlotinib-induced skin inflammation is IL-1 mediated in KC-Tie2 mice and human skin organ culture. J Invest Dermatol 135:910-913
Lundberg, Kathleen C; Fritz, Yi; Johnston, Andrew et al. (2015) Proteomics of skin proteins in psoriasis: from discovery and verification in a mouse model to confirmation in humans. Mol Cell Proteomics 14:109-19
Soler, D C; Bai, X; Ortega, L et al. (2015) The key role of aquaporin 3 and aquaporin 10 in the pathogenesis of pompholyx. Med Hypotheses 84:498-503

Showing the most recent 10 out of 39 publications