Dr. Michael Zuscik, Associate Professor of Orthopaedics, and Director of Educational Programs at the Center for Musculoskeletal Research, will serve as the Principal Investigator for the 2015 CTSI Incubator project. The central focus of Dr. Zuscik’s research can be divided programmatically into two parts: 1) the study of the contribution of chondrogenesis and chondrocyte differentiation to the process of fracture repair and 2) the study of the behavior of the articular chondrocyte under normal conditions in healthy joints and during pathologic situations such as joint degeneration. The complex interplay between several key signaling mechanisms, including the TGF-beta, Wnt/beta-catenin and PTH/PTHrP pathways, are important for modulating chondrocyte differentiation and physiology and thus have a critical contribution to play during the fracture healing and joint maintenance/disease.
Dr. Zuscik will lead a collaborative team of multidisciplinary researchers from various departments across the Medical Center. The co-investigators on the project are:
- Robert Mooney, PhD, Professor of Pathology and Laboratory Medicine
- Cheryl Ackert-Bicknell, PhD, Associate Professor of Orthopaedics
- Brendan Boyce, MD, Professor of Pathology and Laboratory Medicine
- Hani Awad, PhD, Professor of Biomedical Engineering
- Danielle Benoit, PhD, Associate Professor of Biomedical Engineering
- Edward Schwarz, PhD, Director of the Center for Musculoskeletal Research
- Din Chen, PhD, Professor, School of Nursing
The title of their collaborative Incubator project is “Mechanisms of Obesity and Type 2 Diabetes-induced Musculoskeletal Comorbidities.” Breakthrough discoveries made by the group over the past several years have uncovered a previously underappreciated pathological impact of obesity and type 2 diabetes (T2D) on the musculoskeletal system. Among established effects on the cardiovascular and immune systems, it has been established that obesity/T2D impacts musculoskeletal disease burden in the context of accelerated osteoarthritis (OA), increased risk of implant-associated S. aureus infection and osteomyelitis, and delayed bone fracture healing.
Recent progress in these three specific areas has led to the emergence of separate projects within the Center for Musculoskeletal Research, each designed to elucidate the molecular and genetic basis of disease comorbidity as the precursor to translating basic mechanistic information into candidate therapeutic strategies. This program’s design aims to build towards an NIH P01 application, aligns with the institution’s strategic plan to approach systems biology questions using a big-data analytical approach, and accelerates the pace of discovery by translating basic science knowledge into therapeutic approaches with clinical impact via highly collaborative research.
Additionally, this research program aligns with the CTSI’s major initiatives in Community Health focused on obesity/T2DM and it is expected that this project will synergize with these initiatives in the future. Overall, the proposed program will leverage already available NIH P30-supported resources to provide two key Core Services that will support activities in the three projects which include investigations into how obesity/T2D-induced synovial insulin resistance accelerates OA. An investigative and advisory team has been assembled from two institutions and from six departments within the University of Rochester to collaboratively pursue these distinct scientific directions within the overarching theme of investigating the mechanisms underlying the effects of obesity/T2D on the skeleton.