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Professor of Human Genetics Associate Research Scientist for Institute of Gerontology |
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| 5815 Med Sci II 1241 E. Catherine St. SPC 5618 Ann Arbor, MI 48109 -5618 |
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The Burke Laboratory research effort is concentrated in three main areas: (1) the analysis of the stability of gene expression during mammalian aging, (2) quantitative trait locus (QTL) analysis of complex, mulitgenic traits in the laboratory mouse, and (3) the development of engineering systems for microfluidic analysis.
The first research area seeks to understand the genetic mechanisms involved in stabilizing adult gene expression in late-life. We are testing the hypothesis that aging-dependent reactivation is a general phenomenon of transcriptionally repressed genes. Two types of genes show this unusual
expression: (1) genes on the non-pseudoautosomal X chromosome in females (X inactivation), and (2) genes that are differentially expressed based on parent of origin (genomic imprinting). In both epigenetic control systems, we detect a loss of precision with increasing age. We are also measuring
the stability of the messenger RNA alternative splicing process during normal aging.
The second research area, in a collaborative effort with Dr. Richard Miller (University of Michigan, Institute of Gerontology and Department of Pathology) and other investigators at the University of Michigan, is a long-term project to identify regions of the mouse genome correlated with inter-individual variation in aging phenotypes. Several phenotypic indicators of aging are being examined in parallel, including T-cell populations, circulating hormones, bone structure, late-life hearing loss, and cancer incidence. We have identified gene locations associated with several late-life phenotypes, using a reproducible, genetically heterogeneous laboratory mouse population (UM-HET). The third project is a collaborative effort with Dr. Mark Burns (University of Michigan, Department of Chemical Engineering), and is developing a high-throughput DNA genotype analysis system that can be provided to genetics researchers at low cost. The microfluidic devices will: a) require human interaction only for initial loading of samples, b) provide consistent experimental processing and quality control, c) decrease sample processing time and human labor, d) reduce reagent costs by reducing the genotyping biochemistry to nanoliter volumes, and e) be fully controlled by integrated circuitry.
2004 Basic Science Research Award, School of Medicine, University of Michigan
1996-2001 Presidential Faculty Fellow, National Science Foundation
1999 Faculty Recognition Award, University of Michigan
1993-96 Searle Scholar Award, The Chicago Community Trust
1992-94 Basil O'Connor Starter Scholar Award, March of Dimes Birth Defects Foundation
1989-91 Life Sciences Research Foundation Fellow, Howard Hughes Medical Institute
1987 Spencer T. and Ann W. Olin Medical Scientist Fellow, Washington University
1978-82 Joseph C. Wilson Scholar, University of Rochester
1991 Princeton University, Princeton NJ Post-doctoral fellow, Molecular Genetics
1988 Washington University, St. Louis MO, Ph.D., Molecular Biology
1982 University of Rochester, Rochester NY, B.S., Biological Sciences/Biochemistry
Bennett-Baker PE, Wilkowski J, Burke DT: Age-associated activation of
epigenetically repressed genes in the mouse. Genetics, 165:2055-2062, 2003.
Volkman SK, Galecki AT, Burke DT, Paczas MR, Moalli MR, Miller RA,
Goldstein SA: Quantitative trait loci for femoral size and shape in a
genetically heterogeneous mouse population. J. Bone Miner. Res.,
18:1497-1505, 2003.
Harper JM, Galecki AT, Burke DT, Pinkosky SL, Miller RA: Quantitative trait
loci for insulin-like growth factor-I, leptin, thyroxine, and
corticosterone in genetically heterogeneous mice, Physiol. Genomics,
15:44-51, 2003.
Volkman SK, Galecki AT, Burke DT, Miller RA, Goldstein SA: Quantitative
trait loci that modulate femoral mechanical properties in a genetically
heterogeneous mouse population. J. Bone Miner. Res., 19:1497-1505, 2004.
Wolf N, Galecki A, Lipman RD, Chen S, Burke DT, Miller RA. Quantitative
trait locus mapping for age-related cataract severity and synechia
prevalence using four-way cross mice. Invest. Ophth. Visual Sci.,
45:1922-1929, 2004.
Pal R, Yang M, Johnson BN, Burke DT, Burns MA: Phase change microvalve for
integrated devices. Anal. Chem., 76:3740-3748, 2004.
Lin R, Burke DT, Burns MA: Addressable electric fields for size-fractioned
sample extraction in microfluidic devices. Anal. Chem., 77:4338-4347, 2005.
Pal R, Yang M, Lin R, Johnson BN, Srivastava N, Razzacki SZ, Chomistek KJ,
Heldsinger DC, Haque RM, Ugaz VM, Thwar PK, Chen Z, Alfano K, Yim MB,
Krishnan M, Fuller AO, Larson RG, Burke DT, Burns MA. An integrated
microfluidic device for influenza and other genetic analyses. Lab Chip, 5:
1024-1032, 2005.
Krishnan M, Burke DT, Burns MA. Theoretical considerations for counting
nucleic acid molecules in microdevices. J Micromech Microeng 15: N6-N10,
2005
Hanlon P, Lorenz WA, Shao Z, Harper JM, Galecki AT, Miller RA, Burke DT.
Three-locus and four-locus QTL interactions influence mouse insulin-like
growth factor-I. Physiol. Genomics 26: 46-54, 2006.
Reeves GM, McCreadie BR, Chen S, Galecki A, Burke DT, Miller R, Goldstein
S. Quantitative trait loci modulate vertebral morphology and mechanical
properties in a population of 18 month old genetically heterogeneous mice.
Bone 40: 433-443, 2007
Chisa JT, Burke DT. Mammalian mRNA splice-isoform selection is tightly
controlled. Genetics 2007, 175:1079-1087.
Zheng J, Webster JR, Mastrangelo CH, Ugaz VM, Burns MA, David T. Burke DT:
Integrated plastic microfluidic device for ssDNA separation. Sensors and
Actuators B (2007) 125:343-351
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