AT A GLANCE
Assistant professor at the University of Michigan Medical School Department of Psychiatry. Co-directs the departments microarray lab with Fan Meng.
Received his PhD from the department of cell and molecular biology at Oregon Health Sciences University in Portland, Oregon.
Postdoctoral research at the University of Michigan, working in the laboratory of Stan Watson studying genes expressed in the central nervous system.
Research interests include the issue of how stress systems, particularly the brains stress systems, influence reproductive function. One aspect of this research is the way nutritional stress compromises the reproductive system, at the molecular and anatomical level.
QWhat role do microarrays play within the research of the University of Michigan Department of Psychiatry?
AMicroarrays or the manipulation of gene expression might provide us with clues as to how antidepressants act in the central nervous system. In collaboration with my colleague Juan Lopez, I embarked a couple of years ago on an effort to understand how antidepressants act within the central nervous system to influence mood state. Different antidepressants broker the reuptake of seratonin or other neurotransmitters from the synapse. However, once this occurs, the secondary, tertiary, or quaternary effects that lead to altered mood states are largely unknown. We are investigating these effects by running animal studies and using tissues from these studies in our microarray experiments. Also, in a project funded by the Pritzker Foundation, researchers at Michigan , UC Irvine, and UC Davis are studying human brain tissue for similar studies.
QHow is the microarray facility organized within the university?
AWe have eight different microarray facilities on campus. One microarray group studies sensory functions, while still another studies bone or skeletal gene expression, and we have a group specializing in diabetes and one in cancer.
QWhy didnt the different departments just get together and form one core facility?
AFor anyone who has tried to put together a microarray facility, one of the immediate issues you are confronted with is the type of arrays that you are going to produce. If you go with a custom spotted array system, are you going to spot everything? If you lack the capacity to spot everything, how are you going to define the subset to spot? Your choice will depend on whether you are studying cancer, microbiology, or mental illness. By having eight such groups, each can develop arrays specific for its own science. That turned out to be tremendously powerful.
QDo any of the facilities have Affymetrix chips?
AA central Affymetrix facility on the medical campus is about to open. Affymetrix provides researchers with general microarrays for broad gene expression analysis, and the customization of the array format is quite useful as a follow-up or supplement to Affymetrix. We also have high-density cDNA arrays with known genes for users who choose not to go with the Affymetrix platform. These include rat or mouse chips with 10,000 to 15,000 spots.
QWhy would someone choose a homemade cDNA chip over an Affymetrix GeneChip?
AThere is an issue of whether you are going to spot genes with known identifiers or known names, or you are going to dig deep into the EST collection.
In academia, we are sometimes guided by processes that influence our ability to obtain NIH funding. Oftentimes a requirement of NIH funding is to develop hypotheses and perform hypothesis testing. This is difficult to do with ESTs.
QWhat is the biggest challenge of working with microarrays?
ASensitivity. The brain is a complex place, and regions often encompass many different types of cells, only a minor subpopulation of which may be specifically related to a given function. If we cut out a brain region that includes mRNAs for this function, other neurons and glia dilute the neurons and the RNA is virtually undetectable. You can take out a particular neuron with laser capture microdissection, but then if you take that approach, how can you understand a complex disease that involves the interactions between many neurons? I would like for microarrays to improve their sensitivity, because many of the rare RNAs are the pillars of my biology.