The long term objectives of this grant proposal are to allow the applicant to develop into an independent physician scientist. In this proposal we present 3 synergistic mechanisms towards that end. 1) Research plan;The applicant proposes to study the regulation of Th17/Th1 responses in the animal model of collagen induced arthritis. This will be addressed in 3 specific aims:
Specific Aim 1 : To study the changes in Thi7 and Thi responses associated with onset and severity of arthritis following administration of lL-4DCs;
Specific Aim 2 and 3: To understand the regulation of Thi 7 and Thi responses by costimulatory molecules in collagen induced arthritis 2) Formal didactic training: the applicant will enroll in immunobiology courses as well as attend seminars and national meetings. 3) Advisory committee: the applicant has formed an advisory committee to not only provide guidance during this process, but also evaluate her progress towards an independent physician scientist. The applicants training will happen at the University of Arizona, Tucson, Arizona.

Public Health Relevance

Rheumatoid arthritis is associated with pain, swelling, deformity of the hands and feet. The prevalence remains at 1%. A significant proportion of patients do not benefit from the existing therapeutic options. This proposal is focused on identifying and understanding another cytokine, lL-17, that may have a pathogenic role in rheumatoid arthritis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08AR054323-05
Application #
8513916
Study Section
Arthritis and Musculoskeletal and Skin Diseases Special Grants Review Committee (AMS)
Program Officer
Mao, Su-Yau
Project Start
2009-08-01
Project End
2014-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
5
Fiscal Year
2013
Total Cost
$113,211
Indirect Cost
$8,386
Name
University of Arizona
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
806345617
City
Tucson
State
AZ
Country
United States
Zip Code
85721
Sarkar, S; Justa, S; Brucks, M et al. (2014) Interleukin (IL)-17A, F and AF in inflammation: a study in collagen-induced arthritis and rheumatoid arthritis. Clin Exp Immunol 177:652-61
Justa, Shivali; Zhou, Xiaoqun; Sarkar, Sujata (2014) Endogenous IL-22 plays a dual role in arthritis: regulation of established arthritis via IFN-? responses. PLoS One 9:e93279
Sarkar, Sujata; Zhou, Xiaoqun; Justa, Shivali et al. (2013) Interleukin-22 reduces the severity of collagen-induced arthritis in association with increased levels of interleukin-10. Arthritis Rheum 65:960-71
Gizinski, Alison M; Fox, David A; Sarkar, Sujata (2010) Pharmacotherapy: concepts of pathogenesis and emerging treatments. Co-stimulation and T cells as therapeutic targets. Best Pract Res Clin Rheumatol 24:463-77