· Wound healing
· Stem cells
· Neuromuscular disorders
· Musculoskeletal neoplasia
· Musculoskeletal development
· Musculoskeletal repair
· OREF Research Award
· Royal College Medal
· Premier's Research Excellence Award
· Huene Award
The entire wound healing process is a complex series of events that begins at the moment of injury and can continue for months to years. Our goal is to determine the role of Wnt pathway, particularly its key molecule β-catenin, in reconstitution of epithelial and dermal components of the skin during would healing. Using different genetically engineered mouse designed in our lab, we would determine the fate of the cells that contribute in healing and the role of β-catenin in this process.
(Team member: Saeid Amini Nik, Kirsten Bielefeld, Raymond Poon, Puviindran Nadesan, Heather Whetstone)
Stem cells & neoplasia
Stem cells are the earliest step in the hierarchal progressive maturation to functionally differentiated cells with characteristics of self-renew and fast proliferation. Although the concept that tumors contain a subpopulation of cells with stem cell properties has been demonstrated in a number of tumor types, little has been reported on the role of stem cells in musculoskeletal (MSK) tumors, perhaps due to lack of unique mesenchymal stem cell (MSC) marker. In our studies, we hypothesize that MSK tumors contain a subpopulation of cancer initiating cells, with stem cell like properties. Therefore, the first step in our research is to identify and isolate tumor initiating cells (TIC) from musculoskeletal tumors. Further study of this population of cells will allow for the characterization of molecular pathways regulating the development of MSK, ultimately identifying potential novel therapeutic targets.
(Team member: Qingxia Wei, Shingo Sato, Ilkyu han and Ronak Ghanbari)
Within the growth plate, Indian hedgehog (Ihh) regulates chondrocyte proliferation and differentiation that involves a feedback loop with the parathyroid hormone related protein (PTHrP). We have generated transgenic mice showing that a deregulation of Ihh/PTHrP signaling during growth plate development is involved in the development of cartilage tumors. Through investigation of these transgenic mice, we hope to elucidate on the specific role of Ihh signaling during growth plate development.
(Team member: Jason Rockel, Claire Hsu, Louisa Ho, Heather Whetstone)
Joint degeneration & repair
Osteoarthritis (OA) is a degenerative disease of the joint involving the degradation of and inability to regenerate articular cartilage, and subchondral bone changes. We believe that by understanding how joints develop, we can provide new insight and novel therapies for OA. Our current data suggests that Wnt and other signaling pathways involved in normal joint development may be also involved in the development and progression of OA. Therefore, we aim to elucidate how modulating these pathways can provide a mechanism of OA pathology attenuation and enhance joint repair.
(Team member: Peter Kannu, Amanda Ali, Heather Whetstone)
Endochondral ossification is recapitulated during BMP induced ectopic bone formation. Although BMP and β-catenin have been investigated in bone development and in mesenchymal cells, how they interact in this regenerative process is not clear. We therefore aim at investigating how β-catenin pathway regulates bone formation. In addition, although β-catenin signaling pathway, which activates Tcf-dependent transcription, has emerged as a key regulator in embryonic skeletogenesis, its role in bone repair is unknown. Currently, we are working to address if β-catenin signaling pathway plays a crucial role during fracture healing. We also try to figure out if activation of this pathway by lithium, a pharmacologic reagent that has already been used to treat patients with bipolar disease, would substantially improve bone healing. Also, based on traditional concepts, both stem cells and osteoblasts are required to initiate bone healing, however, we hypothesize that stem cells may exert greater potential to trigger bone healing even if osteoblasts are absent. For this propose, we are investigating whether pre-existing osteoblasts indeed play a "must have" role during early fracture repair.
(Team member: Gurpreet Baht, Simon Kelly, Saber Ghadakzadeh, Puviindran Nadesan, Heather Whetstone)