Current Projects & Initiatives
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The mechanism for inflammatory bone loss and the role of calcineurin/NFATc axis in
implant loosening in arthritis patients. This NIH R01 funded project is investigating the
mechanobiological mechanism responsible for hip prosthesis loosening. Orthopaedic
implants are designed to integrate with the host bone under mechanical loading. The use of
biomaterials for hip arthroplasty is a widely accepted treatment for advanced osteoarthritis,
avascular necrosis and hip fractures. However, long-term clinical success is limited by
prosthetic loosening associated with ultrahigh molecular weight polyethylene (UHMWPE)
wear particle-induced inflammatory bone loss and non-integration of host bone-prosthesis.
Polyethylene wear particles are known to stimulate macrophages and osteoblasts to produce
tumor necrosis factor alpha (TNF-ά) and other pro-osteoclastogenic cytokines. Our approach
is to delineate the mechanobiological interaction between biomaterials and the host immune
system to enable the development of engineer techniques that can prevent or treat the
biomaterial-induced inflammatory bone loss by targeting pro-inflammatory pathways.
The role of ERK in inflammatory bone loss in arthritis. The long-range goal of this NIH R01 funded project is to develop a preventive and preemptive strategy against inflammatory bone loss which negatively affects the outcome of patients with arthritis. The specific objective of this project is to define the functionality of ERK in osteoblast-mediated innate immunity in the context of biomaterial by conducting in vivo and in vitro mechanistic experiments. The clinical rationale underlying this study is to prevent or treat the clinically important problem of inflammatory bone loss by targeting osteoblast-mediated immune pathways with specific topical or systemic inhibitors of ERK and associated molecules.
Mesenchymal Stem Cell-Based Adjuvant Therapy for Sarcomas. Most cancer research is concentrated on the more common carcinomas of the breast, lung and kidney. Our cancer research is focused on sarcomas, which are resistant to conventional cancer therapies. Chondrosarcomas in particular are highly resistant to both chemo and radiation therapy, minimizing treatment options. Preliminary work by our lab suggests that chondrosarcoma survival is associated with upregulation of antiapoptotic genes. By silencing antiapoptotic genes we are able to increase the radio- and chemosensitivity of the tumor cells. However, this promising in vitro result is only relevant in a clinical context if a suitable mechanism for delivery to the tumor site is found. Our research team is currently working with human mesenchymal stem cells (hMSCs), which are known to “home” to the site of certain cancers. Our objective is to elucidate the roles of hMSCs in the treatment of musculoskeletal tumors.
The role of ERK in inflammatory bone loss in arthritis. The long-range goal of this NIH R01 funded project is to develop a preventive and preemptive strategy against inflammatory bone loss which negatively affects the outcome of patients with arthritis. The specific objective of this project is to define the functionality of ERK in osteoblast-mediated innate immunity in the context of biomaterial by conducting in vivo and in vitro mechanistic experiments. The clinical rationale underlying this study is to prevent or treat the clinically important problem of inflammatory bone loss by targeting osteoblast-mediated immune pathways with specific topical or systemic inhibitors of ERK and associated molecules.
Mesenchymal Stem Cell-Based Adjuvant Therapy for Sarcomas. Most cancer research is concentrated on the more common carcinomas of the breast, lung and kidney. Our cancer research is focused on sarcomas, which are resistant to conventional cancer therapies. Chondrosarcomas in particular are highly resistant to both chemo and radiation therapy, minimizing treatment options. Preliminary work by our lab suggests that chondrosarcoma survival is associated with upregulation of antiapoptotic genes. By silencing antiapoptotic genes we are able to increase the radio- and chemosensitivity of the tumor cells. However, this promising in vitro result is only relevant in a clinical context if a suitable mechanism for delivery to the tumor site is found. Our research team is currently working with human mesenchymal stem cells (hMSCs), which are known to “home” to the site of certain cancers. Our objective is to elucidate the roles of hMSCs in the treatment of musculoskeletal tumors.
