The primary objective of this mentored career development award in clinical research is for the candidate Dr. Jeffrey Greenberg to acquire the skills and expertise to become an independent investigator in clinical and translational arthritis research. Under the direction of Drs. Steven Abramson and Harry Ostrer, the candidate has constructed a focused training program that will build upon the candidate's prior Masters of Public Health degree in epidemiology and health services research. Selected courses with direct relevance to the current research proposal and anticipated future research directions will include intensive coursework in human genetics and translational research. The didactic component of the training program will also include weekly seminars, regular face-to-face mentor meetings and participation in Dr. Abramson's weekly arthritis laboratory meetings. In addition, this career development program will benefit from the oversight of a carefully selected Advisory Committee of senior research scientists with expertise in clinical and translational research. The research for this proposal will be conducted at three participating sites of the Consortium of Rheumatology Researchers of North America (CORRONA) including NYU, Johns Hopkins and Albany. This prospective cohort study will investigate single nucleotide polymorphisms (SNPs) of candidate inflammatory mediator genes as prognostic biomarkers for RA patients. The three specific aims include: 1) To determine whether genetic biomarkers can predict response to targeted biologic response modifiers;2) To determine whether genetic biomarkers can predict clinical disease activity and radiographic severity;and 3) To determine whether genetic biomarkers can predict the risk of serious infection. Candidate genes will be assessed using high-density single nucleotide polymorphism (SNP) genotyping to facilitate linkage disequilibrium (LD) mapping and extended haplotype construction. Clinical trials of BRM agents indicate that up to one-third of RA patients do not achieve a clinical response, and serious adverse outcomes including infections can occur. Pharmacogenetic studies that can identify genetic biomarkers to """"""""personalize"""""""" the likelihood of clinical response to targeted BRMs, as well as the risk of adverse outcomes, will represent a major advance for the treatment of RA.

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 #
5K23AR054412-04
Application #
7822904
Study Section
Special Emphasis Panel (ZAR1-MLB-L (O1))
Program Officer
Wang, Yan Z
Project Start
2007-04-15
Project End
2012-03-31
Budget Start
2010-04-01
Budget End
2011-03-31
Support Year
4
Fiscal Year
2010
Total Cost
$132,948
Indirect Cost
Name
New York University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
121911077
City
New York
State
NY
Country
United States
Zip Code
10016
Jain, Manish; Attur, Mukundan; Furer, Vika et al. (2015) Increased plasma IL-17F levels in rheumatoid arthritis patients are responsive to methotrexate, anti-TNF, and T cell costimulatory modulation. Inflammation 38:180-6
Solomon, Daniel H; Kremer, Joel M; Fisher, Mark et al. (2014) Comparative cancer risk associated with methotrexate, other non-biologic and biologic disease-modifying anti-rheumatic drugs. Semin Arthritis Rheum 43:489-97
Harrold, Leslie R; Reed, George W; Harrington, J Timothy et al. (2014) The rheumatoid arthritis treat-to-target trial: a cluster randomized trial within the Corrona rheumatology network. BMC Musculoskelet Disord 15:389
Fisher, Mark C; Hochberg, Marc C; El-Taha, Muhammad et al. (2012) Smoking, smoking cessation, and disease activity in a large cohort of patients with rheumatoid arthritis. J Rheumatol 39:904-9
Greenberg, Jeffrey D; Reed, George; Decktor, Dennis et al. (2012) A comparative effectiveness study of adalimumab, etanercept and infliximab in biologically naive and switched rheumatoid arthritis patients: results from the US CORRONA registry. Ann Rheum Dis 71:1134-42
Harrold, Leslie R; Harrington, J Timothy; Curtis, Jeffrey R et al. (2012) Prescribing practices in a US cohort of rheumatoid arthritis patients before and after publication of the American College of Rheumatology treatment recommendations. Arthritis Rheum 64:630-8
Fisher, Mark C; Furer, Victoria; Hochberg, Marc C et al. (2012) Malignancy validation in a United States registry of rheumatoid arthritis patients. BMC Musculoskelet Disord 13:85
Greenberg, Jeffrey D; Kremer, Joel M; Curtis, Jeffrey R et al. (2011) Tumour necrosis factor antagonist use and associated risk reduction of cardiovascular events among patients with rheumatoid arthritis. Ann Rheum Dis 70:576-82
Zhang, Jie; Shan, Ying; Reed, George et al. (2011) Thresholds in disease activity for switching biologics in rheumatoid arthritis patients: experience from a large U.S. cohort. Arthritis Care Res (Hoboken) 63:1672-9
Greenberg, Jeffrey D; Furer, Victoria; Farkouh, Michael E (2011) Cardiovascular safety of biologic therapies for the treatment of RA. Nat Rev Rheumatol 8:13-21

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