Bruce Lahn

Scholar: 2000

Awarded Institution
The University of Chicago
Department of Human Genetics


Research Interests

As a mammalian genetics laboratory, we are engaged in the following areas of research:

1) Molecular dissection of mammalian spermatogenesis.
Mammalian spermatogenesis is a highly complex developmental process, involving such fundamental biological events as mitosis, meiosis, recombination, and epigenetic reprogramming. Our lab is interested in elucidating how spermatogenesis is regulated at the molecular level. Our approach is to isolate genes that play critical roles in spermatogenesis, and characterize their precise function.

2) Uncovering genetic defects underlying male infertility.
Close to 10% of men are estimated to encounter fertility problems. The cause of male infertility is largely unknown. Our lab is attempting to identify genetic defects underlying male infertility by a "candidate gene" approach, which entails searching amongst a large sample collection of infertile men for mutations that disrupt genes with important spermatogenic functions. This search has already uncovered a number of genetic defects that contribute to male infertility. Research is currently underway to determine the precise manner by which these genetic defects result in spermatogenic failure.

3) Elucidating the genetic basis of human intelligence.
A most enduring question of biology is what makes us uniquely intelligent in the animal kingdom. Our lab tackles this question by systematically comparing gene sequences between humans and our primate relatives, and attempting to uncover functionally meaningful mutations that have arisen during the evolution of humans.

4) Rapid cloning of human disease genes.
The ability to identify small heterozygous deletions (deletions affecting one chromosome but not its homolog) in the human genome can be enormously powerful in isolating disease genes, as it eliminates the need for large pedigrees. However, technology for systematically identifying heterozygous deletions is lacking. Our lab is currently developing such techniques, with the ultimate goal of applying them to rapid, large-scale cloning of human disease genes.

5) A system for monitoring gene expression in vivo at the single cell level.
The current technology for monitoring gene expression in vivo involves introducing a promoter-driving-GFP construct into the organism (e.g. mouse). This procedure is laborious, and as a result, has been applied only to a limited number of genes. Our lab is developing a new strategy for monitoring gene expression, which involves an antisense-driving-GFP scheme. Once developed, we hope to apply this technology to the study of a large number of developmentally regulated genes in the mouse and other organisms.