Current Research Interests:
Identification of Genes Involved in Behavior, Neurological,
and Psychiatric Disorders
We are interested in finding genes involved in neurological and psychiatric diseases as well as behavior in general. In contrast to Mendelian single gene defects, human behavior and risk for psychiatric illness such as depression and alcoholism are determined by a complex interaction of environmental and multiple genetic risk factors. With the Human Genome sequenced, unprecedented numbers of genetic variants identified, and novel technologies that allow the study of genetic variants, untangling these risk factors is now possible and has started in my laboratory.
Specifically, we search for risk factors for bipolar disorder in several larger collaborations. In addition, we also search for genetic variants that influence traits related to psychiatric disorders: For example, high scores on the personality domain “neuroticism” are indicative of increased risk for depression. Thus, we search for association between genetic variants in candidate genes for depression with neuroticism in a large population sample. Similarly, impulsivity and low executive control functions are indicators of increased risk of substance abuse. We genetically analyze a large sample of families at high risk for substance abuse. In addition, we search for genetic variants associated with drug response in depression.
In a large collaboration, we combine genetic with microarray expression analysis of postmortem brains of subjects that died with depression and control subjects. We determine genetic variants that influence gene expression in brains.
While primarily interested in human disorders, we are using mice as a model system when appropriate. We use genetic methodologies and have identified specific single gene mutations that cause ataxia, seizures, and behavioral abnormalities in mice and humans. For some of these, the function of the encoded protein is unknown, and we are starting to clarify this function. We collaborate with clinicians, psychologists, epidemiologists, statisticians and bioinformaticians as well as other geneticists in these endeavors.
- Faculty member of interdisciplinary graduate programs: Neuroscience and Bioinformatics.
- Diplom (Master) in Biochemistry, Free University of Berlin and Weizman Institute of Science, Rehovot, Israel.
- Ph.D., European Molecular Biology Laboratory (EMBL) and University of Heidelberg.
- Postdoctoral Fellow, University of California San Francisco.
Honors and Awards:
Fellow of the "Studienstiftung des Deutschen Volkes" (German Phi Beta Kappa Equivalent).
Minerva (German Israeli Exchange) Fellowship.
Postdoctoral Fellowship from the German Academic Exchange Committee (DAAD).
NARSAD Young Investigator (twice) and NARSAD independent Investigator (twice)
March of Dimes Basil O'Connor Starting Investigator Award.
Klingenstein Fellowship Award in the Neurosciences.
Alexander von Humboldt Foundation Fellowship for Sabbatical in Berlin, Germany.
Selected Publications:
Sliwerska E, Meng F, Speed T, Jones E, Bunney W, Akil, H, Watson S, Burmeister M: SNPs on Chips: The hidden genetic code in expression arrays. Biological Psychiatry, in press 2006.
Li J and Burmeister M: Genetical Genomics: Combining genetics with gene expression analysis. Human Molecular Genetics 10: 14: R163-R169, 2005.
Seong, E., Wainer, B. H., Hughes, E. D., Saunders, T. L., Burmeister, M., and Faundez, V. Genetic Analysis of the Neuronal and Ubiquitous AP-3 Adaptor Complexes Reveals Divergent Functions in Brain. Mol. Biol. Cell 16: 128-140, 2005.
Sen S, Burmeister M, Ghosh D: Meta-Analysis of the Association Between a Serotonin Transporter Promoter Polymorphism (5-HTTLPR) and Anxiety-Related Personality Traits. Amer. J. Med. Genet. (Neuropsychiatric Genetics): 127B1: 85-89, 2004.
Sen S, Villafuerte S, Nesse R, Stoltenberg SF, Hopcian J, Gleiberman L, Weder AB and Burmeister M : Serotonin Transporter and GABA(A) α6 Receptor Variants are Associated with Neuroticism. Biol. Psych. 55(3): 244-249, 2004.
Bomar JM, Benke PJ, Slattery EL, Puttagunta R, Taylor LP, Seong E, Nystuen A, Chen W, Albin RL, Patel PD, Kittles RA, Sheffield VC, Burmeister M: Mutations in a novel CRAL-TRIO domain encoding gene cause human Cayman Ataxia and ataxia/dystonia in the jittery mouse. Nature Genetics 35: 264-269, 2003.
Links to additional information about the work of Dr. Burmeister.
Department of Psychiatry, University of Michigan
Genetics: The Symphony of Life; University of Michigan Health System
Department of Human Genetics, University of Michigan
Figure 1: Multiple risk factors for depression
Depression is thought to be caused by a combination of genetic factors, early experiences and stressful life events. Instead of comparing depressed subjects and controls, research on the genetics of personality can get at genetic predisposition genes for depression even while studying a general population sample.
(from: http://www.med.umich.edu/genetics/faculty/burmeister.htm)
Figure 2: The critical regions of Cayman Ataxia and the
jittery mousemutation overlap.
Physical maps of human 19p13.3 and mouse chromosome 10 showing (blue arrows) the regions to which the disorders have been localized. The green bar indicates a map inversion we identified previously, whereas the red bar is the region of overlap. The enlarged region shows the genes in the overlap. Atcay is the gene identified as the jittery and Cayman ataxia gene in our studies (see paper by Bomar et al., Nature Genetics 2003)
Figure 3. Distinctive phenotypes of isoform specific AP-3 deficiencies.
(A) Ap3b1 -/- mice have lighter coat and skin (ear, tail) colors, but Ap3b2 -/- mice,
generated in Dr. Burmeister’s laboratory by gene targeting, have normal pigmentation, indistinguishable from the control. (B) Open field test.
Ethovision animal behavior analysis software was used to automatically measure
horizontal movement. Distance moved for every 5 min is plotted for 100 min.
Ap3b2 -/- animals were twice as active during the first 30 min. After 50 min,
their activity was not significantly different from control ( *p < 0.01).
Eleven control, 10 Ap3b1 -/-, and 11 Ap3b2 -/- mice were tested.
(see paper by Seong et al., 2005) |
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