Abstract

The primary interest of my group is bone growth and mammary gland tumorigenesis usinganimal 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 asintracellular 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 geneBrca1 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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Intramural Research (Z01)
Project #
1Z01DK056001-02
Application #
6432177
Study Section
(GDDB)
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2000
Total Cost
Indirect Cost

  Institution

Name
U.S. National Inst Diabetes/Digst/Kidney
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Lahusen, Tyler J; Deng, Chu-Xia (2015) SRT1720 induces lysosomal-dependent cell death of breast cancer cells. Mol Cancer Ther 14:183-92
Cao, Liu; Xu, Xiaoling; Cao, Longyue L et al. (2007) Absence of full-length Brca1 sensitizes mice to oxidative stress and carcinogen-induced tumorigenesis in the esophagus and forestomach. Carcinogenesis 28:1401-7
Tominaga, Y; Wang, A; Wang, R-H et al. (2007) Genistein inhibits Brca1 mutant tumor growth through activation of DNA damage checkpoints, cell cycle arrest, and mitotic catastrophe. Cell Death Differ 14:472-9
Park, Changwon; Lavine, Kory; Mishina, Yuji et al. (2006) Bone morphogenetic protein receptor 1A signaling is dispensable for hematopoietic development but essential for vessel and atrioventricular endocardial cushion formation. Development 133:3473-84
De Soto, Joseph A; Deng, Chu-Xia (2006) PARP-1 inhibitors: are they the long-sought genetically specific drugs for BRCA1/2-associated breast cancers? Int J Med Sci 3:117-23
Oppermann, Mona; Mizel, Diane; Huang, George et al. (2006) Macula densa control of renin secretion and preglomerular resistance in mice with selective deletion of the B isoform of the Na,K,2Cl co-transporter. J Am Soc Nephrol 17:2143-52
Tominaga, Yohei; Li, Cuiling; Wang, Rui-Hong et al. (2006) Murine Wee1 plays a critical role in cell cycle regulation and pre-implantation stages of embryonic development. Int J Biol Sci 2:161-70
Israelsson, Charlotte; Lewen, Anders; Kylberg, Annika et al. (2006) Genetically modified bone morphogenetic protein signalling alters traumatic brain injury-induced gene expression responses in the adult mouse. J Neurosci Res 84:47-57
Shukla, Vivek; Coumoul, Xavier; Cao, Liu et al. (2006) Absence of the full-length breast cancer-associated gene-1 leads to increased expression of insulin-like growth factor signaling axis members. Cancer Res 66:7151-7
De Soto, Joseph A; Wang, Xianyan; Tominaga, Yohei et al. (2006) The inhibition and treatment of breast cancer with poly (ADP-ribose) polymerase (PARP-1) inhibitors. Int J Biol Sci 2:179-85

Showing the most recent 10 out of 96 publications