Research

Cartilage Molecular Genetics Group

David Hall, Ph.D.
Group Leader, Cartilage Molecular Genetics Group
Cartilage Biology and Orthopaedics Branch (CBOB)
Phone: (301) 451-6860
Fax: (301) 480-4315
E-mail: halld@mail.nih.gov

Research Focus

Musculoskeletal diseases such as arthritis constitute the major debilitating diseases in adult humans. To better understand the causes of this disease the research in my laboratory is centered on understanding the genetic basis of cartilage formation and homeostasis. Our goals are to identify genes that will aid in the formation of cartilage in cell culture and to use this newly formed cartilage in a tissue-engineering context to replace the worn out cartilage resulting from osteoarthritis. Towards this end we use adult human mesenchymal stem cells as a cellular source to form cartilage in cell culture. In concert with this process, we have begun to utilize a genetic engineering approach to modify existing cartilage proteins, such as the transcription factor Sox 9 and the extracellular matrix factor cartilage oligomeric matrix protein (COMP), so that we will be able to generate cartilage more efficiently in cell culture and that the cartilage formed will be better able to function when implanted into the body.

Another ongoing project is to utilize genetic screens to identify genes that will help cartilage be more resistant to the factors that cause arthritis. These genetic screens have never been used to date in an orthopaedic or cartilage biology setting and therefore have enormous potential to aid in the discovery of new genes that will benefit halt the onset of osteoarthritis.

Finally, we are setting out to explore the protective role of cartilage proteins in cancer. We are testing the hypothesis that certain cartilage proteins such as COMP limit the growth of cancer cells. In this way there may be an inverse relationship between arthritis and cancer such that the former may protect against the latter. Our initial investigations suggest that such a relationship may exist.

Photo of Use of Bone-Derived MSCs and Chondrogenesis in Vitro; Treatment for Osteoarthritis.


Selected Publications

Tuli R, Nandi S, Li WJ, Tuli S, Huang X, Manner PA, Laquerriere P, Noth U, Hall DJ, Tuan RS. Human Mesenchymal Progenitor Cell-Based Tissue Engineering of a Single-Unit Osteochondral Construct. Tissue Eng. 2004; 10(7): 1169-1179. PubMed Icon

Tuan RS, Eyre D, Schurman DJ. Biology of developmental and regenerative skeletogenesis. Clin Orthop. 2004; (427 Suppl): S105-17. PubMed Icon

Wang ML, Tuli R, Manner PA, Sharkey PF, Hall DJ, Tuan RS. Direct and indirect induction of apoptosis in human mesenchymal stem cells in response to titanium particles. J Orthop Res. 2003; 21(4):697-707. PubMed Icon

Rallapalli R, Strachan G, Tuan RS, Hall DJ. Identification of a domain within MDMX-S that is responsible for its high affinity interaction with p53 and high-level expression in mammalian cells. J Cell Biochem. 2003; 89(3):563-75 PubMed Icon

Noth U, Tuli R, Seghatoleslami R, Howard M, Shah A, Hall DJ, Hickok NJ, Tuan RS. Activation of p38 and Smads mediates BMP-2 effects on human trabecular bone-derived osteoblasts. Exp Cell Res. 2003; 291(1): 201-11. PubMed Icon

See complete list of publications

 

Updated October 10, 2007