Thomas E. Wilson, M.D., Ph.D.

Thomas Wilson, M.D., Ph.D.

Professor of Pathology
Professor of Human Genetics

2065 BSRB
109 Zina Pitcher Place
Ann Arbor, MI 48109-2200

734-764-2212

Administrative Contact

Michele Pushies

Areas of Interest

1) Mechanistic studies of DNA double-strand break repair: DNA double-strand breaks (DSBs) occur frequently and can be lethal if not repaired. Inappropriate repair can lead to chromosomal rearrangements. Understanding the dynamics of these events requires a detailed understanding of the molecular mechanisms of two competing DSB repair pathways, nonhomologous end-joining (NHEJ) and homologous recombination. We use genetic approaches, mainly in yeast, to identify novel components of these pathways and characterize their modes of action. Current focus is on DNA ligase IV, the lynchpin enzyme of NHEJ, resection of DSB ends, and nuclear influences on translocation frequency.

2) Impacts of DNA repair and transcription on copy number variant hotspots and fragile sites: The global effect of deficient DSB repair on genome stability has historically been difficult to assess, but high-throughput genome analysis tools, including microarrays and next-generation sequencing, now allow us to look in an unbiased manner at the relationships between DNA damage, repair, and chromosomal aberrations. Recent findings highlight that mammalian “fragile sites” are hotspots for copy number variant (CNV) formation under replication stress in a manner dependent on the active transcription of very large genes. We are working to describe the mechanisms by which transcription and replication interact throughout the cell cycle to promote genome structural alteration. This work has a strong bioinformatics component coupled with human cell and animal wet-lab experimentation.

3) The dynamic process of global gene expression: Our group is an active partner in the development of novel nascent RNA sequencing methods, especially Bru-seq, which allow us to examine the dynamic process of transcription and also the downstream stability of RNA transcripts. Major goals relate to understanding the factors that influence RNA polymerase transcription initiation and timely traversal through genes, and how these processes are both altered by and contribute to genomic DNA damage and mutagenic repair events.

Honors & Awards

  • President, Environmental Mutagenesis and Genomics Society
  • Endowment for the Basic Sciences Faculty Teaching Award in Human Genetics
  • Environmental Mutagenesis and Genomics Society (EMGS) Service Award
  • Pew Scholars Program in the Bio-medical Sciences
  • Biological Sciences Scholars Program, University of Michigan

Credentials

  • B.S., Biochemistry, University of Wisconsin, 1983-1987 
  • Ph.D., Neural Sciences, Washington University School of Medicine, 1987-1994 
  • M.D., Washington University School of Medicine, 1987-1994 
  • Residency, Laboratory Medicine, Washington University School of Medicin, 1994-1999 
  • Postdoctoral Fellow, Laboratory of Dr. Michael Lieber, Washington University School of Medicine, 1995-1999
  • Chief Resident, Laboratory Medicine, Washington University School of Medicine, 1998-1999 

Published Articles or Reviews

Liang Z, Sunder S, Nallasivam S, Wilson TE: Overhang polarity of chromosomal double-strand breaks impacts kinetics and fidelity of yeast non-homologous end joining. Nucleic Acids Res: 2016. PM26773053

Magnuson B, Veloso A, Kirkconnell KS, Lima LC, Paulsen MT, Ljungman EA, Bedi K, Prasad J, Wilson TE, Ljungman M: Identifying transcription start sites and active enhancer elements using BruUV-seq. Sci Rep 5: 17978, 2015. PM26656874/PMC4675984

Wilson TE, Arlt MF, Park SH, Rajendran S, Paulsen M, Ljungman M, Glover TW: Large transcription units unify copy number variants and common fragile sites arising under replication stress. Genome Res 25(2): 189-200, 2015. PM25373142

Chiruvella KK, Renard BM, Birkeland SR, Sunder S, Liang Z, Wilson TE: Yeast DNA ligase IV mutations reveal a nonhomologous end joining function of BRCT1 distinct from XRCC4/Lif1 binding. DNA Repair (Amst) 24: 37-45, 2014. PM25457772

Veloso A, Kirkconnell KS, Magnuson B, Biewen B, Paulsen MT, Wilson TE, Ljungman M: Rate of elongation by RNA polymerase II is associated with specific gene features and epigenetic modifications. Genome Res 24(6): 896-905, 2014. PM24714810

Arlt MF, Rajendran S, Birkeland SR, Wilson TE, Glover TW: Copy number variants are produced in response to low-dose ionizing radiation in cultured cells. Environ Mol Mutagen 55(2): 103-13, 2014. PM24327335

Paulsen MT, Veloso A, Prasad J, Bedi K, Ljungman EA, Magnuson B, Wilson TE, Ljungman M: Use of Bru-Seq and BruChase-Seq for genome-wide assessment of the synthesis and stability of RNA. Methods 67(1): 45-54, 2014. PM23973811

Chiruvella KK, Liang Z, Wilson TE: Repair of double-strand breaks by end joining. Cold Spring Harb Perspect Biol 5(5): a012757, 2013. PM23637284

Veloso A, Biewen B, Paulsen MT, Berg N, Carmo de Andrade Lima L, Prasad J, Bedi K, Magnuson B, Wilson TE, Ljungman M: Genome-wide transcriptional effects of the anti-cancer agent camptothecin. PLoS One 8(10): e78190, 2013. PM24194914

Chiruvella KK, Liang Z, Birkeland SR, Basrur V, Wilson TE: Saccharomyces cerevisiae DNA ligase IV supports imprecise end joining independently of its catalytic activity. PLoS Genet 9(6): e1003599, 2013. PM23825968

Arlt MF, Rajendran S, Birkeland SR, Wilson TE, Glover TW: De novo CNV formation in mouse embryonic stem cells occurs in the absence of Xrcc4-dependent nonhomologous end joining. PLoS Genet 8(9):e1002981, 2012. PM23028374

Arlt MF, Wilson TE, Glover TW: Replication stress and mechanisms of CNV formation. Curr Opin Genet Dev 22(3): 204-210, 2012. PM22365495

Arlt MF, Ozdemir AC, Birkeland SR, Wilson TE, Glover TW: Hydroxyurea induces de novo copy number variants in human cells. Proc Natl Acad Sci USA 108(42): 17360-17365, 2011. PM21987784

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