Medical Student Research Fellowship for Summer 2010

Mentor: Heidi Jacobe
Department: Dermatology
Room number: JA5.120H
Mail Code: 9069
Phone number: 214-648-2985
E-mail: Heidi.Jacobe@UTSouthwestern.edu

Project I title: Protein microarray for determination of autoantibody reactivity in localized scleroderma.

Human subjects IRB approved project number (where applicable): 032007-021

Animal subjects IRB approved project number (where applicable): NA

Project Type patient-based research and 2nd translational research

Brief Description of Project:

Morphea is currently classified into 5 subtypes based on the clinical appearance of the lesions. To date, there have been no consistent correlations between disease subtypes and autoantibody profiles in terms of prognosis, response to therapy, or correlation with disease activity. There are case reports and small case series indicating certain autoantibodies may indicate disease activity or prognosis, but their characterization is incomplete. In order to: 1) identify novel autoantibody associations in morphea
2) determine whether significant differences exist in autoantibody reactivity between morphea subtypes and healthy controls, we did a pilot study using a proteosome microarray developed by Quan Li in the UTSW Microarray Core (Noori Kim's project). This study provided preliminary data identifying putative novel autoantibodies in morphea and signatures specific to morphea subsets (presented as a poster at the ACR by Noori Kim).

Ms. Geng's project represents the second phase of this project. I have received funding to characterize autoantibody profiles utilizing proteosome microarray for the entire UTSW Morphea Registry cohort. Ms. Geng will work with Drs. Olsen, Li, and I to design the microarray run encompassing our entire cohort. The student will use existing sera and data from the UT Southwestern Morphea Registry. She will then work with us in analyzing this data and correlating findings to the clinical phenotype of the patient. Further, these results will be correlated with the autoantibodies determined via traditional assays and emerging RNA microarray data.

Aims for This Project:

1. To validate our initial findings from the pilot study in a larger group of patients including:
" Novel autoantibody associations (anti PDGFR, collagens, and the like).
" Different patterns of autoantibody reactivity in morphea subtypes vs. normal controls.
2. In addition, Ms. Geng will explore 2 new areas of interest:
" Comparison of autoantibody reactivity patterns in morphea vs. scleroderma (sera provided through collaboration with the Scleroderma Registry, Maureen Mayes) using proteosome microarray
" And correlation of RNA microaaray data with changes in protein microarray.

Student role for project: The student will be directly responsible for working with the Microarray Core Facility and mentor in designing the experiment for proteosome microarray and analyzing the data as well as correlating findings with clinical phenotype.

Project II title: Cross-sectional study of patients currently enrolled in Morphea Registry to examine the impact of morphea on quality of life.

Human subjects IRB approved project number (where applicable): 032007-021

Animal subjects IRB approved project number (where applicable): NA

Project Type patient-based research and 2nd translational research

Brief Description of Project and Student Role:

Ms. Schaefer will be conducting a cross sectional study of patients currently enrolled in the Morphea Registry (220 individuals) examining the impact of morphea on quality of life (specifically impact on physical function, social function, ability to work/go to school, and psychological impact). The project will entail Ms. Schaefer contacting patients currently enrolled in the Registry (IRB approved) and asking them to fill out validated QOL instruments (SF 36, SKINDEX, and DLQI) as well as 3 write in questions specific to morphea domains. Ms. Schaefer will then enter the data into our existing Microsoft Access Database. With my help, as well as a known expert in QOL measures in dermatology, (Mary Margaret Chren) she will analyze the data specifically looking for effect of age, race, and gender on QOL in morphea. Further, she will correlate disease characteristics (subtype, body surface area involvement, site of involvement, presence of systemic disease, presence of functional impairment) with score of each instrument. These data points already exist in the Registry database. To date, there is only one published paper addressing these issues in morphea. This study will be significant in the following ways:

1. It will provide data on which QOL instrument best captures disease burden and impact in morphea.
2. It will provide an estimate of the impact of this disease on patients which can be compared to the impact of other dermatologic (via DLQI and SKINDEX score) and systemic disorders (SF36).
3. It will determine which disease attributes are most burdensome to patients, providing parameters for development of disease outcome measures and refinement of therapy.

Previous Research Activities or Publications with Medical Students:

Doris Duke Foundation Clinical Research Fellows

Doris Duke fellow 2007-2008
Rachael Cayce
A retrospective review of the epidemiologic and autoimmune characteristics of morphea patients.
Poster Presentation SID, Kyoto, Japan, May 2008
Leitenberger J, Cayce R, Haley RW, Adams-Huet B, Bergstresser PR Jacobe H. Morphea subtypes are distinct autoimmune syndromes: A review of 245 adult and pediatric cases. Arch Dermatol 2009 May; 145(5) 545-50.

Doris Duke fellow 2006-2007
Justin Leitenberger (UT Houston)
A retrospective review of the epidemiologic and autoimmune characteristics of morphea patients.
Poster Presentation SID, Los Angeles, CA, 2007.
Leitenberger J, Cayce R, Haley RW, Adams-Huet B, Bergstresser PR Jacobe H. Morphea subtypes are distinct autoimmune syndromes: A review of 245 adult and pediatric cases. Arch Dermatol 2009 May; 145(5) 545-50.

Third and Fourth Year Dermatology Elective

Noori Kim, fall 2008 - Protein microarray signatures in morphea. Abstract 2nd poster presentation, International Congress of Dermatology, Prague, Czech, May 2009, and ACR Annual Meeting, Philadelphia, PA, October 2009.

Shadi Kourosh, summer 2008 - Carpel tunnel syndrome as a presenting sign of scleroderma. Manuscript in preparation, Archives Internal Medicine.

Second Year Summer Research Fellowship

Siewee Lee, 2008
Mona Sadgephour, 2008 (Yale University School of Medicine)
Aimee (Heewon) Kwak, 2008
Julie Nguyen, 2007 - Jacobe HT, Nguyen J, Cayce R. UVA1 phototherapy is effective in darker skin: A review of 101 patients of Fitzpatrick skin types I-V. Br J Dermatol 159(3):691-696, 2008

Angela Brimhall
Summer 2004
Metaanalysis of biologics for psoriasis
Manuscript submitted for publication, British J of Dermatol. Brimhall A, King L, Licciardone J, Jacobe H, Menter A: Safety and efficacy of alefacept, efalizumab, etanercept and infliximab in treating moderate to severe plaque psoriasis: A meta-analysis of randomized controlled trials. Br J Dermatol 159(2):24-85, 2008.

Angela Escobar
Summer 2004
A comparison of medium high dose UVA, phototherapy for the treatment of morphea.
Manuscript in preparation.