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.
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