MICHAEL NASKI, M.D., Ph.D.
Assistant Professor
Phone 210-567-4126
FAX 210-567-4819
e-mail: naski@pathology.uthscsa.edu

Degrees

1990, Ph.D., University of Michigan
1991, MD, University of Michigan

Postdoctoral Training

1992-96, House Officer, Anatomic Pathology, Barnes Hospital/Washington University
1994-98, Postdoctoral Fellow, Washington University
1998-99, Surgical Pathology Fellow, Barnes Hospital/Washington University

Description of Research

   A template constructed of cartilage defines the pattern of the vertebrate skeleton. Mesenchymal cells under the control of regional morphogenetic and proliferative cues coalesce and secrete an extracellular matrix that forms this template. As the cells aggregate, those at the center become surrounded by an extracellular matrix and differentiate into chondrocytes.
   Our continuing objective is to understand the pathways that regulate the differentiation of mesenchymal cells to the chondrocyte lineage and the differentiation of chondrocytes during the process of endochondral bone growth. To better understand these pathways of cell differentiation, we are examining the transcriptional control of chondrocyte-specific gene expression. We hypothesize that there are concerted transcriptional pathways controlling chondrocyte differentiation and that these pathways act on chondrocyte specific genes like fibroblast growth factor receptor 3 (FGFR3) and aggrecan. The expression of both genes is initiated early and maintained throughout the cascade of chondrocyte differentiation. Thus they are likely targets for transcriptional pathways of chondrogenesis. We have found that the MADS box transcription factor, serum response factor, is an important determinant of FGFR3 gene expression. We are currently characterizing its interactions with other transcriptional regulators of FGFR3. Aggrecan, the major proteoglycan of cartilage is similarly regulated by serum, as well certain growth factors like fibroblast growth factor 2 and bone morphogenetic protein 2. We have identified a 500 bp cis-acting element in the aggrecan gene that can confer expression in chondrocytic cells. We are currently characterizing the role of certain DNA recognition motifs with the 500 bp elements as well as the cognate transcriptional regulators.

Selected References

Naski, M.C., Wang, Q., Xu, J. & Ornitz, D.M. Graded activation of fibroblast growth factor receptor 3 by mutations causing achondroplasia and thanatophoric dysplasia Nature Genetics 13, 233-237 (1996)