Area of interest
My current research is directed towards annotation of the genome by attempting to establish the affects of common sequence variation on phenotype. In contrast to the approach, used by most investigators, of trying to find the sequence variations that cause a specific disease each of my projects is analyzing a large set of traits that are common in the population. The rational is that it is more likely that relationships between genotype and phenotype can be found if there are more phenotypes to analyze. Another theme in my work is to try to increase the power of detecting an association between a phenotype and genotype by exploring phenotypic space to define the optimal phenotype that segregates with alternative alleles.
While having an interest in many areas of medicine and genetics my group has focused on two major areas: genetics of non-Alzheimer dementia and genetics of addiction. Our recent work has utilized highly automated microsatellite genotyping for chromosome segregation analysis. We developed automation for high throughput genotyping that determined millions of microsatellite genotypes per year. Using data we collected we have identified chromosome locations for genes that affect susceptibility to our phenotypes of interest.
To extend this work we need to develop the capacity for high-density extremely high capacity single nucleotide polymorphism genotyping. This effort can be logically extended to include whole genome association analysis so that a systematic search can be made for common gene variants that affect phenotypes of interest. Many Cancer Center investigators also need the ability to be able to perform whole genome analysis. By combining the effort of many investigators this will become possible in the near future.
My own interest in cancer research dates back to my undergraduate research on the ability of SV40 to cause transformation of cells in culture. This led to my decision to become a graduate student in the lab of Howard Temin where I cloned c- and v-rel (aka NF-B) for my thesis work. More recently, during the last five years I have been actively trying to map genes that affect smoking behavior. This work has led us to a few chromosomal regions were we think it is very likely that there are genes with polymorphism that have a moderate affect on maintenance nicotine dependence. In the next few years we are planning to systematically screen genes in these regions for sequence variants that modulate smoking behavior.
Awards and Honors
1984 Price Award for Cancer Research
1986 Forester Award for Neurology
1991 Klingenstein Fellow Award
1990-94 Herbert Irving Assistant
Professor of Neurology
1999 Potamkin Prize for Neurology
1999 Decade of the Brain Lecture at the AAN