Professor of Medicine and Developmental Biology
Department of Orthopaedics
Washington University School of Medicine
Dr. Long is an ideal example of how the BIRCWH program has directed the research career of an outstanding young scientist toward research relevant to women’s health. An elite molecular biologist, Fanxin could have joined the faculty in an environment focused exclusively on basic signaling mechanisms. Instead, Dr. Long was recruited from Harvard to Washington University as an Assistant Professor in the Bone and Mineral Division (a recruitment enhanced by the possibility of funding through the BIRCWH program), where his talents in intracellular signaling could be applied to an area directly relevant to women’s health, osteoporosis.
As a BIRCWH Scholar, Dr. Long continued to develop his interests in fundamental developmental biology of cell differentiation as it applies to osteoblasts and bone formation. The osteoblast is the primary cell type that creates new bone and impairment in osteoblast function leads to osteoporosis. Using several mouse models, Dr. Long’s research has elegantly dissected many of the signaling pathways responsible for osteoblast differentiation. His studies have implicated intercellular signals such as Wnt, Hedgehog, Bmp, and Notch in distinct stages of skeletal formation. The Long lab provides an outstanding training environment for IWHR Scholars interested in applying the modern tools of developmental biology to the understanding of osteoporosis.
BIRCWH Scholar from 04/1/2003 until 12/31/2003
Towards A Molecular Understanding Of The Regulation Of Osteogenesis By Indian Hedgehog
The molecular mechanism for osteogenesis in mammals is not well understood. Much of the mammalian skeleton is derived from a cartilage template via endochondral bone formation. In the limb, osteoblasts first develop from the perichondrium, and this process requires direct input of Indian hedgehog, a signal produced by chondrocytes. It is unknown how hedgehog signaling regulates osteogenesis. In the following proposal, I test the hypothesis that Indian hedgehog regulates transcription of target genes, which in turn determine differentiation of osteoblasts.
1) Using gene chip technology, I will compare mRNA species between samples where hedgehog signaling is activated and those where it is not.
2) By performing in situ hybridization on tissue sections and real-time PCR on cell cultures, I will examine the expression of genes identified in Specific Aim 1).
3) Using siRNA (small interfering RNA) technique, I will examine the function of the genes identified in Specific Aim 2) in hedgehog-induced osteogenesis in C3H10T1/2 cells.