The primary interest of my group is bone growth and mammary gland tumorigenesis using animal model systems. We have the following three projects. 1. Functions of fibroblast growth factor receptors (FGFRs). FGFRs constitute a family of 4 membrane-spanning tyrosine kinases, which serve as high affinity receptors for at least eighteen growth factors (FGF1-21). It has been shown that mutations in FGF receptors are responsible for at least nine human inherited diseases, all of which are caused by single amino acid mutations and exhibit extensive craniofacial, axial and/or appendicular bone abnormalities. To study functions of FGFs/FGFRs signals in development and to gain insights into mechanisms underlying these inherited diseases, mice carrying a variety of mutations including complete, isoform and conditional knockouts, and point mutations that mimic the human diseases have been created through gene targeting. Functional analysis of these mutant mice is being carried out. 2. Functions of Smad genes. Smads constitute of a gene family of 9 members that serve as intracellular mediators of TGF-b signals. We have generated mouse mutants carrying targeted mutations in SMAD2-6. Our preliminary analysis on the mutant mice has revealed distinct functions of these genes in multiple biological processes. 3. Functions of Brca1 gene. We are studying functions of the breast tumor suppressor gene Brca1 in mammary gland development and tumor formation. Breast cancer is the most common cancer and the second leading cause of cancer mortality in women, with approximately one in 9 being affected over their lifetime. Analyzing our Brca1-null, isoform or conditional knockout models, we showed that BRCA1 is essential for genetic stability. Loss of BRCA1 increases mutation rates of all genes, including tumor suppressors and oncogenes, which result in tumor formation. We are continuing to study mechanisms of BRCA1 associated tumorigenesis and seeking efficient ways to prevent the transformation process from happening.
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