David R. Beier

Department of Medicine
Brigham and Women's Hospital
Harvard Medical School
New Research Building, Room 458D
77 Avenue Louis Pasteur
Boston, MA 02115
Tel: (617) 525-4715
Fax: (617) 525-4705
Email: beier@receptor.med.harvard.edu
6 postdoctoral fellows

My research utilizes genetic analysis of the mouse as a means to study fundamental problems in mammalian biology. This usually involves the characterization, mapping, and positional cloning of novel murine mutations. We have also used genetic analysis to characterize complex traits, such as modifier loci affecting the progression of polycystic kidney disease and interacting loci causing asthma in a mouse model.

Our major research effort is a screen for recessive ENU-induced mutations of late embryonic development, with the aim to identify models of human malformation syndromes which affect organogenesis. We have identified mutations affecting the development of the neural tube and brain, the heart, the diaphragm and lungs, the skeletal system, the craniofacial system, and the kidneys. As part of this project we are adapting a strategy of SNP genotyping that allows us to rapidly map new mutations using small numbers of affected progeny. We have been able to take advantage of the rapid progress in the generation of mammalian genome sequence and the computational tools for its analysis to pursue molecular characterization of these novel mutants, and we anticipate that this will be a valuable resource for understanding organ development.

References:

• Herron BJ, Lu W, Rao C, Liu S, Peters H, Bronson RT, Justice MJ, McDonald JD, Beier DR. Efficient generation and mapping of recessive developmental mutations using ENU mutagenesis. Nature Genetics 2002; 30:185-9.
• Ackerman, K, Herron BJ, Vargas S, Huang H, Kochilas L, Rao C, Pober P, Babiuk R, Epstein J, Greer J, Beier DR. Fog2 is required for Normal Diaphragm and Lung Development in Mice and Man. PLoS Genetics 2005; 1:58-65.
• Moran JL, Bolton AD, Tran PV, Brown A, Dwyer ND, Manning DK, Li C, Montgomery K, Siepka SM, Vitaterna MH, Takahashi JS, Wiltshire T, Kwiatkowski DJ, Kucherlapati R, Beier DR. Utilization of a whole genome SNP panel for efficient genetic mapping in the mouse. Genome Research 2006; 16:436-40.
• Tran PV, Haycraft CJ, Besschetnova TY, Turbe-Doan A, Stottmann RW, Herron BJ, Chesebro AL, Qiu H, Scherz PJ, Shah JV, Yoder BK, Beier DR. THM1 negatively modulates mouse Sonic Hedgehog signal transduction and affects retrograde intraflagellar transport in cilia. Nature Genetics 2008; 40:403-10.