Associate Professor

Orthopaedics and Rehabilitation

Center for Musculoskeletal Research

University of Rochester Medical Center (Rochester, NY)

Director: Histology, Biochemistry, and Molecular Imaging Core

Center for Musculoskeletal Research

University of Rochester Medical Center (Rochester, NY)

Notch regulation of skeletal development and disease

Most of the bones in the vertebrate skeleton arise from a cartilage template during embryogenesis. This process, known as endochondral ossification, begins with the differentiation of condensed mesenchymal stem cells (MSCs) into chondroprogenitors (immature cartilage cells) and osteoprogenitors (immature bone cells). Both the chondroprogenitor and osteoprogenitor cells undergo a coupled proliferation and differentiation program ultimately leading to the formation of mature cartilage and bone. Various genetic studies have demonstrated that Ihh, Pthrp, BMPs, FGFs, and canonical Wnt signaling pathways are required at multiple stages of normal cartilage and bone development. Deregulation of these signaling circuits during development are a primary cause for a variety of skeletal dysplasias, as well as, age related cartilage and bone pathologies.

A long-term interest of the Hilton lab is to uncover the molecular circuitry regulating lineage commitment, proliferation, and differentiation of MSCs and maturing chondrocytes. My laboratory uses genetic mouse models and primary cell culture techniques coupled with biochemistry to answer questions regarding MSC self-renewal/differentiation, chondrogenesis, and chondrocyte maturation. Recently my lab has generated novel data from a variety of Notch gain and loss-of-function mutant mice demonstrating that Notch signaling pathway suppresses MSC differentiation and plays critical roles in regulating chondrogenesis and chondrocyte maturation. We are currently investigating the exact Notch signaling mechanisms regulating both early and late stages of these processes, as well as, determining how Notch components interact with other known signaling pathways during cartilage development and maintenance. These studies are also being extended to aid in our mechanistic understanding of both fracture repair and osteoarthritis.

2008 ASBMR Harold M. Frost Young Investigator Award

2004 ASBMR Young Investigator Award