This K08 proposal details a comprehensive five-year plan for Dr. Ali Jabbari's career development in basic and translational research in Dermatology. Dr. Jabbari is an early career physician scientist in the Department of Dermatology at Columbia University. Dr. Jabbari's prior clinical and research experience has him uniquely positioned to study alopecia areata (AA), an autoimmune disease in which the hair follicle is the target of attack. Despite its high prevalence, there are no evidence-based treatments for AA. Studies in a C3H/HeJ AA mouse model have shown that the development of AA is critically dependent on the T-helper 1 (Th1)-associated cytokine interferon-?, and an initial microarray-based assessment of gene expression signatures in the skin of a limited number of human subjects with AA identified the presence of a prominent interferon signature. Dr. Jabbari's proposal addresses the role of IL-12, a prototypical Th1 cytokine, in the pathogenesis of AA. Additionally, he will compare the transcriptional profile of AA, generated from dozens of samples collected through the National Alopecia Areata Registry, to publically available profiles from archetypal Th-associated inflammatory skin diseases. In this proposal, Dr. Jabbari proposes to (i) assess the role of IL-12 in AA development using genetic models of AA, (ii) assess the use of anti-IL- 12 or anti-IL-12R antibodies for therapeutic purposes in AA, and (iii) conduct transcriptomic comparisons of human AA with prototypical Th-associated skin diseases and an IL-12 gene signature. Results from this proposal address the pivotal role IL-12 may be playing in AA and may identify Th-associated signature heterogeneity among human AA samples. This mentored award will provide the training framework for transitioning into an independent position. His mentors will be Dr. Angela Christiano, an internationally-recognized skin and hair biologist and translational scientist, and Dr. Andrea Califano, a renowned expert in systems biology whose interests reside in the assembly and interrogation of gene regulatory models for the elucidation of mechanisms presiding over cell physiology and their dysregulation in disease. Dr. Yong-Guang Yang, Director of the Humanized Mouse Core Facility and head of a laboratory that focuses on transplantation and acute graft versus host disease, will also serve as an advisor for Dr. Jabbari's training plan. The comprehensive training plan described within is critical for Dr. Jabbari's transition to an independent scientist and to position him for applying for a career in academic dermatology.

Public Health Relevance

This K08 proposal is designed to assess the role of a particular molecule, interleukin-12, on the development of alopecia areata, a common autoimmune disease that results in hair loss. We postulate that interleukin-12 is a necessary part of the disease process and may be a potential target for treatments.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08AR069111-03
Application #
9274151
Study Section
Special Emphasis Panel (ZAR1)
Program Officer
Cibotti, Ricardo
Project Start
2016-07-01
Project End
2021-06-30
Budget Start
2018-07-01
Budget End
2019-06-30
Support Year
3
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of Iowa
Department
Dermatology
Type
Schools of Medicine
DUNS #
062761671
City
Iowa City
State
IA
Country
United States
Zip Code
52242
de Jong, Annemieke; Jabbari, Ali; Dai, Zhenpeng et al. (2018) High-throughput T cell receptor sequencing identifies clonally expanded CD8+ T cell populations in alopecia areata. JCI Insight 3:
Dai, Zhenpeng; Xing, Luzhou; Cerise, Jane et al. (2016) CXCR3 Blockade Inhibits T Cell Migration into the Skin and Prevents Development of Alopecia Areata. J Immunol 197:1089-99
Jabbari, Ali; Cerise, Jane E; Chen, James C et al. (2016) Molecular signatures define alopecia areata subtypes and transcriptional biomarkers. EBioMedicine 7:240-7
Kennedy Crispin, Milène; Ko, Justin M; Craiglow, Brittany G et al. (2016) Safety and efficacy of the JAK inhibitor tofacitinib citrate in patients with alopecia areata. JCI Insight 1:e89776
Jabbari, Ali; Nguyen, Nhan; Cerise, Jane E et al. (2016) Treatment of an alopecia areata patient with tofacitinib results in regrowth of hair and changes in serum and skin biomarkers. Exp Dermatol 25:642-3
Mackay-Wiggan, Julian; Jabbari, Ali; Nguyen, Nhan et al. (2016) Oral ruxolitinib induces hair regrowth in patients with moderate-to-severe alopecia areata. JCI Insight 1:e89790