I am a rheumatologist and PhD-trained epidemiologist who has devoted my career to patient-oriented research (POR) focused on osteoarthritis (OA) and gout, two of the most common rheumatologic conditions, which contribute to pain, functional limitations, and diminished quality of life. My training has not only positioned me well to pursue high quality POR, but has also provided me with the necessary skills to train the next generation of clinical scientists. Over the past decade, I have demonstrated a strong commitment to mentorship though mentoring or co-mentoring 21 trainees in POR. These mentoring activities have led to successful funding for the majority of those mentees, including a junior faculty with a fundable K23 score. Further, all continue to perform clinical research, with all but one conducting Rheumatology-related research, and 4 current medical resident mentees are interested in pursuing clinical research careers in Rheumatology. This K24 award would enable me to expand and extend these successful mentoring endeavors so that I may serve as primary mentor to a greater number of mentees by ensuring that I have protected time and relief from future clinical and administrative duties. The broad goals of this K24 grant are to: 1) support my continued development and impact as a primary mentor in POR with a new focus on junior faculty, particularly K applicants and awardees, and those transitioning from K to R awards; 2) establish a new formal research mentor training program for POR in Rheumatology at Boston University School of Medicine (BUSM); and 3) enhance my own POR in a novel direction so that I continue to conduct scientifically rigorous and meaningful POR. With my commitment to POR and mentoring to date, the rich resources available at BUSM and the Clinical Epidemiology Unit, and strong institutional support, the K24 provides an invaluable opportunity to expand my mentoring capacity of junior faculty as primary mentor, with a special emphasis on women clinical researchers, and to establish a specialized structured POR and mentor training curriculum in Rheumatology with formal evaluation of mentees and mentors. In addition to mentoring, one of my long-term goals is to continue advancing my recognized research capabilities. The research proposed leverages my established expertise in OA and gout, and collaboration with experts in the field who have complementary proficiencies to strengthen my research program. Supported by strong biologic rationale, I propose to study the interrelationship between urate (the pathophysiologic culprit in gout) and OA using novel technologies. I will examine the relation of local urate deposition within the knee joints of 3000 subjects in a large NIH-funded cohort study using a novel imaging technology, dual-energy CT, which enables differentiation of urate from other forms of crystal deposition such as calcium, to OA pathology on MRI and to pain. I will also conduct a state-of-the-art proteomic analysis of synovial fluid to discern the impact of urate on inflammatory mediators in knee OA synovial fluid, and the relation to inflammatory features in OA, such as synovitis. The knowledge gap to be addressed by the proposed research will provide novel insights into a potentially new therapeutic target in OA, a disease for which there are currently no therapies available. Moreover, the proposed research will provide excellent mentoring opportunities. This K24 grant would greatly augment my existing research mentoring program in POR by enabling me to recruit and act as primary mentor to 2-3 new trainees and junior faculty annually, with the ultimate goal of developing the next generation of patient-oriented rheumatic disease clinical investigators and research mentors.

Public Health Relevance

Public Health Relevance: Knee osteoarthritis is a leading cause of disability in the US and globally, largely due to knee pain, yet fundamental knowledge regarding what causes osteoarthritis and pain are lacking, hampering the development of rational pain treatment options. This project would build on previous work by the applicant and others to examine the role of urate, which causes gout (another common rheumatic condition) and is treatable, in triggering inflammation, joint damage, and knee pain in people with knee osteoarthritis. Furthermore, these studies will allow the applicant to continue and expand her successful mentoring of junior investigators in patient-oriented research focused on improving the lives of millions of Americans suffering from osteoarthritis, and training the next generation of clinical research mentors in Rheumatology.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
5K24AR070892-04
Application #
9825384
Study Section
Arthritis and Musculoskeletal and Skin Diseases Special Grants Review Committee (AMS)
Program Officer
Zheng, Xincheng
Project Start
2017-02-01
Project End
2022-06-30
Budget Start
2020-07-01
Budget End
2021-06-30
Support Year
4
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Boston University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
Wohlfahrt, Alyssa; Bingham 3rd, Clifton O; Marder, Wendy et al. (2018) Responsiveness of Patient Reported Outcomes Measurement Information System (PROMIS) Measures in RA Patients Starting or Switching a DMARD. Arthritis Care Res (Hoboken) :
Felson, David T; Neogi, Tuhina (2018) Emerging Treatment Models in Rheumatology: Challenges for Osteoarthritis Trials. Arthritis Rheumatol 70:1175-1181
Macri, E M; Felson, D T; Ziegler, M L et al. (2018) The association of frontal plane alignment to MRI-defined worsening of patellofemoral osteoarthritis: the MOST study. Osteoarthritis Cartilage :
Dua, Anisha B; Neogi, Tuhina; Mikolaitis, Rachel A et al. (2018) Somatosensation in OA: exploring the relationships of pain sensitization, vibratory perception and spontaneous pain. BMC Musculoskelet Disord 19:307
Cohen, Ezra M; Edwards, Robert R; Bingham 3rd, Clifton O et al. (2018) Pain and Catastrophizing in Patients With Rheumatoid Arthritis: A Prospective Observational Cohort Study. J Clin Rheumatol :
Abhishek, Abhishek; Neogi, Tuhina; Choi, Hyon et al. (2018) Review: Unmet Needs and the Path Forward in Joint Disease Associated With Calcium Pyrophosphate Crystal Deposition. Arthritis Rheumatol 70:1182-1191
Stefanik, Joshua J; Felson, David T; Apovian, Caroline M et al. (2018) Changes in Pain Sensitization After Bariatric Surgery. Arthritis Care Res (Hoboken) 70:1525-1528
Vargas-Santos, Ana Beatriz; Peloquin, Christine E; Zhang, Yuqing et al. (2018) Association of Chronic Kidney Disease With Allopurinol Use in Gout Treatment. JAMA Intern Med 178:1526-1533
Zhang, MaryAnn; Solomon, Daniel H; Desai, Rishi J et al. (2018) Assessment of Cardiovascular Risk in Older Patients With Gout Initiating Febuxostat Versus Allopurinol. Circulation 138:1116-1126
Choi, Hyon; Neogi, Tuhina; Stamp, Lisa et al. (2018) New Perspectives in Rheumatology: Implications of the Cardiovascular Safety of Febuxostat and Allopurinol in Patients With Gout and Cardiovascular Morbidities Trial and the Associated Food and Drug Administration Public Safety Alert. Arthritis Rheumatol 70:1702-1709

Showing the most recent 10 out of 24 publications