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Cartilage Basic Science Research
Mechanical Models of Arthritis
Mechanical Force and Signaling Pathways in Cartilage Molecular
Mechanisms of OA Progression
The overall goal of this project is to advance the understanding of the molecular mechanisms of osteoarthritis (OA) progression through the novel finding that mechanical force activates critical cellular-signaling pathways in cartilage. A primary goal proposed here is the analysis of the outcomes of these signaling events on the expression and activities of certain degradative enzymes (matrix metalloproteinases, MMPs), which are known to be the major effectors of OA.
Biopsychosocial predictors of functional outcome, cost, and utilization in chronic musculoskeletal conditions
Role of physical activity and self-care in functional outcome
eHealth interventions to support self-care and tertiary prevention in aging, chronic disease populations
Patricia Franklin is Director of Clinical and Outcomes Research and a member of the core faculty of the PhD in Clinical and Population Health Research. She has extensive experience in the analysis and interpretation of clinical and outcome data and is particularly interested in post-total joint replacement functional gains. With her colleagues, she has conducted a series of funded studies to evaluate the contribution of the patient’s physical and emotional health and daily activity to long-term function after total knee replacement (TKR), Medicare’s highest volume procedure. Dr. Franklin currently serves as Principal Investigator on the AHRQ-funded program project grant: Improving orthopedic outcomes through a national TJR registry. UMMS leads this national research effort to define patient-centric outcomes after TJR to better understand predictors of pain relief, gains in physical function, work productivity, and to identify reasons for disparity in TJR use. Dr. Franklin and colleagues are also conducting an NIH trial to evaluate a program to enhance patient adherence to optimal levels of home exercise and physical activity in the TKR rehabilitation period. Dr. Franklin’s eHealth research includes a multi-site RCT testing the efficacy of brief emails to facilitate diet and physical activity change (funded by the Robert Wood Johnson Foundation Health e-Technologies Initiative). Recently the RWJF funded her team to transform population data into web-based outcome prediction tools that will allow patients and physicians to anticipate individualized functional gains after TKR. She is also collaborating in the development of technology for patients to monitor and trend pain and function in personal and electronic health records. While her research focuses on patients with advanced knee arthritis and TKR, each of these eHealth interventions can be extrapolated to self-care in the aging adult.
Leslie Harrold is an Associate Professor of Orthopedics and Physical Rehabilitation at the University of Massachusetts Medical School, and a Senior Research Associate at the Meyers Primary Care Institute (a joint endeavor of the University of Massachusetts Medical School, the Fallon Foundation and Fallon Community Health Plan). She is a board-certified rheumatologist, an epidemiologist and a health services researcher. Dr. Harrold has extensive experience using administrative claims data as well as registry data to identify patients with rheumatic conditions, assess their medication usage, health care utilization and outcomes. She is interested in improving quality of care and patient’s ability to manage his or her own condition. She has received a mentored career development award from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS AR053856); this research focus on medication adherence in gout based on pharmacy dispensings at two health plans and on identifying the patient and provider barriers to optimal care though use of in-depth interviews and questionnaires. She is also a co-investigator on FORCE-TJR, a nationwide registry examining the outcomes of total joint replacement surgery (PI Patricia Franklin) including pain, function and adverse events; she leads the collection of the clinical data to both identify and confirm adverse events.
Cancer Cell Biology in The Bone Microenvironment
Cancer cells cause destruction of the bone, resulting in fractures and severe pain. Understanding the mechanisms which induce metastasis of the primary cancer cell to the bone environment needs to be addressed. We have identified high expression levels of the Runx2 transcription factor in metastatic breast and prostate cancer cell lines. Runx target genes in the cancer cell include the entire class of matrix metalloproteinases characterized for their role in tissue invasion, the vascular endothelial growth factor, a potent angiogenic factor involved as a primary event in tumor growth and several cell growth and osteoblastic genes expressed in the bone environment that allow for tumor growth (Pratap et al., 2005). The cancer cell responds to TGFb and BMP growth factors in the bone extracellular matrix and stimulates bone resorbing cells. In recent studies, we have shown metastatic cancer cell lines in which Runx2 activity has been blocked through genetic mutations, that the osteolytic disease of breast cancer cells can be prevented in the mouse (Barnes et al., 2004; Javed et al., 2005). The presence of mutant Runx2 protein in metastatic cells inhibits cell invasion (in vitro assays) and genes associated with tumor growth. We are now turning our attention to mechanisms responsible for activation of Runx2 in the primary tumor that would lead to the metastatic event in vivo. Experimental approaches include generation of human cancer cell lines with mutants of Runx2, assessing tumor growth by in vivo imaging of tumors in breast, prostate and bone tissues, and examining gene expression profiles of the tumors are assayed.
Dr Nguyen's interest is in the application of epidemiologic and analytic methods to the studies of musculoskeletal and arthritic disorders, and elucidating possible mechanisms for the consequences of these conditions. Areas of research include osteoarthritis and inflammatory arthritis in relation to pain, function, falls, and joint replacement, with current studies focusing on the risk factor paradoxes in rheumatic disease research
Synthetic extracellular matrix analogs for guiding the repair and regeneration of musculoskeletal tissues
With a growing and aging population, the demand for synthetic grafts assisting the repair and reconstruction of musculoskeletal tissue defects induced by trauma, aging, cancer and metabolic diseases is quickly rising. Our lab is interested in designing synthetic extracellular matrix (ECM) analogs capable of promoting the repair or guiding the regeneration of musculoskeletal tissues. These synthetic constructs are also programmed with unique physical properties to facilitate surgical handling (e.g. deployable, elastic, injectable) and proper in vivo degradation characteristics.
Dr Zheng's major research interest is clinical research informatics, including design, implementation, and usability evaluation of patient-centric applications, integration of electronic health records and patient-reported outcomes, and data governance and data quality management in clinical research. Currently she leads user interface design and data management in the AHRQ-funded national research program: Function and Outcomes Research for Comparative Effectiveness in Total Joint Replacement (FORCE-TJR).