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• genetics, genomics and molecular biology
• cell and developmental biology/regenerative medicine
• bioengineering/medical devices

• Medicine
• Sports and Exercise Medicine

• Cardiology
• Clinical Trials
• Orthopaedic surgery
• Rheumatology

My primary research interest is the development of innovative medicines to treat major diseases using adult stem cells (mesenchymal stem/stromal cells (MSCs) or MSCs derived from induced pluripotent stem cells and gene therapy as a means to provide new modalities in patient care for osteoarthritis, bone repair and vascular calcification. Clinical research focuses on the therapeutic potential of MSCs in osteoarthritis. Basic research is focused on the (1) concept that stem cell depletion, or loss/alteration of function, contributes to development of chronic diseases such as osteoarthritis and atherosclerosis, (2) the use of chondrogenic differentiation of bone marrow-MSCs as a model to study early changes that occur in osteoarthritis development/calcification and (3) the role of inflammation in disease progression. Tissue engineering concepts are targeted at 1) development of novel materials for cartilage repair, 2) the use of MSCs and implant surface modification for increased implant osseointegration joint replacement surgeries and 3) the development of targeting strategies and drug delivery modalities for non-invasive delivery of therapeutic cells and/or anti-inflammatory, pro-chondrogenic drugs to joints using micro- and nano-particles. Applied research focuses on scalable, robotic manufacturing of therapeutic MSCs and addresses novel fully defined serum/medium for cell growth and scale-up for economic manufacture.

Blood vessel calcification is a feature of atherosclerosis in cardiovascular disease (CVD) and diabetes, and a predictor of adverse events. Current treatments cannot reverse vascular calcification, the molecular and cellular basis of which is not understood although associated with inflammation. We have shown that resident, vascular stem cells in atherosclerotic mice undergo differentiation to calcifying cells, a process which was promoted by inflammatory mediators. The proposed project will extend this observation to a more clinically relevant model: human vascular stem cells (VSCs) will be isolated from calcified heart valves and varicose veins, as a control patient cell source, and characterized for calcifying potential. These cells will be used as a cellular model to identify inflammatory mediators of calcification. An increased risk of cardiovascular disease is associated with decreased life expectancy in rheumatoid arthritis (RA) patients. Biologic therapies that decrease inflammation in RA and other diseases will be screened for their ability to modulate calcification using the developed in vitro model. Candidate therapies will be assessed in vivo by their ability to prevent atherosclerosis in mouse models of atherosclerosis.