HomeResearchIntramural ResearchResearch Branches at NHGRIGenome Technology Branch Brody Lab

Lawrence C. Brody, Ph.D. Senior Investigator Genome Technology Branch Head Molecular Pathogenesis Section B.S. Pennsylvania State University, 1982 Ph.D. Johns Hopkins University, 1991 (301) 496-7824 (301) 402-2471 (Lab) (301) 480-2592 lbrody@helix.nih.gov Building 50, Room 5306 50 South Drive MSC 8004 Bethesda, MD 20892-8004 Selected Publications Breast Cancer Information Core

We will soon know the sequence of all human genes. However, the identification and evaluation of human gene variants important to health has not kept pace. Likewise, our ability to deduce the function of novel genes remains limited. Research in the Molecular Pathogenesis Section is focused on defining genetic variations that underlie disease and understanding the mechanism by which these variant alleles produce disease. To accomplish this we use research tools traditionally associated with diverse disciplines such as genetic epidemiology, evolutionary biology, cell biology, biochemistry and physiology. This integrated approach, combining investigation into genetics (i.e., variation) and biology (i.e., function), allows us to take maximum advantage of the wealth of data produced by the Human Genome Project (HGP).

One of our research interests is the study of the genes BRCA1 and BRCA2 and their role in inherited breast and ovarian cancer susceptibility. While the link between these genes and cancer risk is well established, we have limited knowledge of the penetrance and function of these genes. Several years ago, our laboratory discovered that specific BRCA1 mutations are present at a high frequency in the Ashkenazi Jewish population. This finding allowed us to measure the risk associated with these mutations in an unselected population. We are continuing to study this population in order to better understand the risk of cancer associated with these mutations, and to identify additional genes that may modify this risk. We are also investigating the biological function of the BRCA1 gene. We recently found that this gene plays an important role in the regulation of the cell cycle.

Our second area of interest is the identification of genes associated with the risk of neural tube defects (NTDs). These defects are a major public health concern, yet the pathogenesis of NTDs is poorly understood. We are searching for genes controlling NTD risk in a large series of affected families. This multi-disciplinary project is a collaboration involving investigators at the National Institute of Child Health and Human Development (NICHD), the Health Research Board of Ireland, and Trinity College-Dublin. Past research established that perturbations of the metabolic pathways involving folate, vitamin B12 and homocysteine can account for a large fraction of NTD cases. The genes making up these metabolic pathways are logical candidates for putative "NTD genes." We identified human genetic variants in the majority the genes comprising these pathways. We are currently measuring the frequency of these variants in NTD families and controls. In addition to measuring the connection between specific variants and the risk of having an NTD, we plan to measure the biochemical and functional consequences of these variants in experimental models and in the patients who carry them.

Top of page

Last Updated: June 2004