The purpose of this application is to support my advanced training in patient-oriented research with the goal of becoming an independently funded investigator studying the epidemiology, immune profiles, and genetics of morphea in adults and children. I will achieve this objective with the help of a rich and supportive environment at the University of Texas Southwestern Medical Center (my institution) which includes: an experienced mentoring committee representing national experts in my fields of interest;a robust training nfrastructure through the Department of Clinical Sciences'Clinical Scholars Program;and an NIH NCRR linded Clinical and Translational Science Award (CTSA) supporting clinical research. These local resources are complemented by the University of Texas Health Science Center in Houston, also the recipient of a TSA award directed by one of my principle mentors, Dr. Frank Arnett. The training program detailed herein as well as the proposed research, represent the inaugural collaborative efforts between two geographically adjacent CTSA centers;which is a mandate and priority for CTSA awards. The Department of Dermatology has committed its full support to my training as a clinical investigator through its sponsorship of my participation in the Clinical Scholars Program (which requires salary support and 75% protected time to pursue training and a research project), access to the departmental clinical research center as well and its outstanding research coordinator, and the active dermatology practice for subject recruitment. The mentored research project that I will conduct in conjunction with my formal training in clinical research nvolves the epidemiology, autoantibody profiles, and immunogenetics of morphea. Morphea is characterized by thickening and hardening of the skin affecting both adults and children and has serious sequelae in terms of joint, limb, and facial deformities producing pain and functional impairment. At this time, there is controversy regarding the exact implications of morphea in terms of its risk for the development of other diseases, either autoimmune or systemic;if there are characteristic autoantibodies or HLA types associated with the disease that may predict disease activity or outcome;and the natural history of the disease. This confusion impairs the appropriate treatment of morphea patients, who suffer serious consequences from either over or under treatment. Having gained initial research experience in this area, I aim to conduct a case control study examining the frequency of systemic and autoimmune disease, presence of autoantibodies, and HLA associations in morphea patients vs. healthy and scleroderma (putatively the systemic form of morphea) controls. Morphea subjects enrolled in the first phase of the study will be asked to continue in a prospective cohort study for ascertainment of the natural history of the disease and if the characteristics measured at baseline predict these outcomes. Design and implementation of this study along with the training activities listed above will develop skills in epidemiological research as well as the translational research skills necessary to investigate the mechanistic aspects of my discoveries including immunogenetics, autoantibody characterization, and genetic epidemiology, thus launching a successful career as an independent clinical investigator.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23AR056303-05
Application #
8307243
Study Section
Arthritis and Musculoskeletal and Skin Diseases Special Grants Review Committee (AMS)
Program Officer
Witter, James
Project Start
2008-08-01
Project End
2014-07-31
Budget Start
2012-08-01
Budget End
2014-07-31
Support Year
5
Fiscal Year
2012
Total Cost
$115,510
Indirect Cost
$8,556
Name
University of Texas Sw Medical Center Dallas
Department
Dermatology
Type
Schools of Medicine
DUNS #
800771545
City
Dallas
State
TX
Country
United States
Zip Code
75390
Klimas, N K; Shedd, A D; Bernstein, I H et al. (2015) Health-related quality of life in morphoea. Br J Dermatol 172:1329-37
Kim, Andrew; Marinkovich, Nicholas; Vasquez, Rebecca et al. (2014) Clinical features of patients with morphea and the pansclerotic subtype: a cross-sectional study from the morphea in adults and children cohort. J Rheumatol 41:106-12
Vasquez, Rebecca; Jabbar, Aysha; Khan, Fatima et al. (2014) Recurrence of morphea after successful ultraviolet A1Ć½Ć½phototherapy: A cohort study. J Am Acad Dermatol 70:481-8
Jacobe, Heidi; Ahn, Chul; Arnett, Frank C et al. (2014) Major histocompatibility complex class I and class II alleles may confer susceptibility to or protection against morphea: findings from the Morphea in Adults and Children cohort. Arthritis Rheumatol 66:3170-7
Grabell, Daniel; Hsieh, Clifford; Andrew, Rachel et al. (2014) The role of skin trauma in the distribution of morphea lesions: a cross-sectional survey of the Morphea in Adults and Children cohort IV. J Am Acad Dermatol 71:493-8
Das, Shinjita; Bernstein, Ira; Jacobe, Heidi (2014) Correlates of self-reported quality of life in adults and children with morphea. J Am Acad Dermatol 70:904-10
Condie, Daniel; Grabell, Daniel; Jacobe, Heidi (2014) Comparison of outcomes in adults with pediatric-onset morphea and those with adult-onset morphea: a cross-sectional study from the morphea in adults and children cohort. Arthritis Rheumatol 66:3496-504
Dharamsi, Jennifer Warner; Victor, Sandra; Aguwa, Nancy et al. (2013) Morphea in adults and children cohort III: nested case-control study--the clinical significance of autoantibodies in morphea. JAMA Dermatol 149:1159-65
Zwischenberger, Brittany A; Jacobe, Heidi T (2011) A systematic review of morphea treatments and therapeutic algorithm. J Am Acad Dermatol 65:925-41
Saxton-Daniels, Stephanie; Jacobe, Heidi T (2010) An evaluation of long-term outcomes in adults with pediatric-onset morphea. Arch Dermatol 146:1044-5

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