Matthew Hilton, Ph.D.

Matthew Hilton, Ph.D.

Contact Information

University of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box 665
Rochester, NY 14642

Office: (585) 275-1335
Fax: (585) 275-1121

Lab Information

The Center for Musculoskeletal Research houses nearly 75 MD and PhD researchers and graduate and post-doctoral students. This team has been one of the top orthopaedics labs in the country since 2000.

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Research Bio

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.
Finally, the Hilton lab is continuing to investigate the molecular mechanisms responsible for a developmental bone and cartilage disorder known as Multiple Hereditary Exostoses (MHE). MHE is an autosomal dominant disease caused by mutations in either the Ext1 or Ext2 genes, subunits of the heparan sulphate co-polymerase complex. Affected individuals are diagnosed with cartilaginous bony outgrowths (exostoses) adjacent to the growth plates of endochondral bones, bowing of some bones, and short stature. Although previous studies have shown that defects in Ext1 and Ext2 lead to reduced synthesis and shortened heparan sulphate chains on cell surface proteoglycans, the exact molecular mechanisms underlying this skeletal disease are still unknown. My lab is currently examining various Ext1 conditional mutant mouse models to determine the precise cell lineage and cause of exostosis formation. Additional genetic studies are also aimed at determining the effect that loss of Ext1 function has on specific signaling pathways important during chondrocyte and osteoblast development.

Awards & Honors (National)

Harold M. Frost Young Investigator Award | American Society of Bone and Mineral Research 2008
ASBMR Young Investigator Award | American Society of Bone and Mineral Research 2004
National Research Service Award Fellowship | Washington University 2004 - 2007
Department of Biology Teaching Excellence Award | University of Houston 2003

Awards & Honors (Local)

Society for Developmental Biology - Southwest Meeting 2000
Order of Omega Leadership and Service Honor Society 1998
Omicron Delta Kappa Leadership Honor Society 1997
University of Miami Dean's List | University of Miami 1994 - 1995
University of Miami Provost's Honor Roll | University of Miami 1994
Henry King Stanford Academic Scholarship 1994 - 1998

Recent Journal Articles

Showing the 5 most recent journal articles. 34 available »

2014 Apr
Jones KB, Pacifici M, Hilton MJ. "Multiple hereditary exostoses (MHE): elucidating the pathogenesis of a rare skeletal disorder through interdisciplinary research." Connective tissue research.. 2014 Apr; 55(2):80-8. Epub 2014 Feb 12.
2014 Mar
Long T, Zhu Z, Awad HA, Schwarz EM, Hilton MJ, Dong Y. "The effect of mesenchymal stem cell sheets on structural allograft healing of critical sized femoral defects in mice." Biomaterials.. 2014 Mar; 35(9):2752-9. Epub 2014 Jan 03.
2014
Mack SA, Maltby KM, Hilton MJ. "Demineralized murine skeletal histology." Methods in molecular biology.. 2014 1130:165-83.
2014
Rutkowsky T, Sharma D, Hilton MJ. "Whole-mount in situ hybridization on murine skeletogenic tissues." Methods in molecular biology.. 2014 1130:193-201.
2014
Mirando AJ, Dong Y, Kim J, Hilton MJ. "Isolation and culture of murine primary chondrocytes." Methods in molecular biology.. 2014 1130:267-77.

Current Appointments

Associate Professor - Department of Orthopaedics, Center for Musculoskeletal Research (SMD) - Primary

Education

PhD | Biology | Univ of Houston2004
BS | Biology | University of Miami1998

Post-Doctoral Training & Residency

Postdoctoral Fellowship | Washington University School of Medicine - St. Louis, MO | Mentor: Fanxin Long, Ph.D. 2007