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Molecular and Cellular Biosciences at Wake Forest University

Wake Forest University Graduate School » Molecular and Cellular Biosciences

Thomas Hollis, Ph.D.

Thomas Hollis, Ph.D.
Education & Training BS Florida State University 1992 PhD University of Texas-Austin 1997 Fellowship Protein Biochemistry Harvard Medical School 2002 Memberships American Crystallographic Association American Society of Biochem & Molecular Biology



Pryor EE Jr, Waligora EA, Xu B, Dellos-Nolan S, Wozniak DJ, Hollis T. The transcription factor AmrZ utilizes multiple DNA binding modes to recognize activator and repressor sequences of Pseudomonas aeruginosa virulence genes. PLoS Pathog. 2012;8(4):e1002648.


Pryor EE Jr, Wozniak DJ, Hollis T. Crystallization of Pseudomonas aeruginosa AmrZ protein: development of a comprehensive method for obtaining and optimization of protein-DNA crystals. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2012;68(Pt 8):985-993.


Coffin SR, Hollis T, Perrino FW. Functional consequences of the RNase H2A subunit mutations that cause Aicardi-Goutieres syndrome. J Biol Chem. 2011;286(19):16984-91.


Fye JM, Orebaugh CD, Coffin SR, Hollis T, Perrino FW. Dominant mutations of the TREX1 exonuclease gene in lupus and Aicardi-Goutieres syndrome. J Biol Chem. 2011;286(37):32373-82.



Powell RD, Holland PJ, Hollis T, Perrino FW. Aicardi-Goutieres syndrome gene and HIV-1 restriction factor SAMHD1 is a dGTP-regulated deoxynucleotide triphosphohydrolase. J Biol Chem. 2011;286(51):43596-600.




Waligora EA, Ramsey DM, Pryor EE Jr, Lu H, Hollis T, Sloan GP, Deora R, Wozniak DJ. AmrZ beta-sheet residues are essential for DNA binding and transcriptional control of Pseudomonas aeruginosa virulence genes. J Bacteriol. 2010;192(20):5390-5401.


Pence MG, Blans P, Zink CN, Hollis T, Fishbein JC, Perrino FW. Lesion bypass of N2-ethylguanine by human DNA polymerase Iota. J Biol Chem. 2009;284(3):1732-1740.


Vasilyeva A, Clodfelter JE, Rector B, Hollis T, Scarpinato KD, Salsbury FR Jr.Small molecule induction of MSH2-dependent cell death suggests a vital role of mismatch repair proteins in cell death. DNA Repair. 2009;8(1):103-113.


Perrino FW, Harvey S, Shaban NM, Hollis T. RNaseH2 mutants that cause Aicardi-Goutieres syndrome are active nucleases. J Mol Med. 2009;87(1):25-30.


de Silva U, Perrino FW, Hollis T. DNA binding induces active site conformational change in the human TREX2 3'-exonuclease. Nucleic Acids Res. 2009;37(7):2411-2417.


Lee-Kirsch M, Gong M, Chowdhury D, Senenko L, Engel K, De Silva U, Bailey SL, Harvey S, Hollis T, Perrino FW, et al. Mutations in the 3 '-5 ' DNA exonuclease TREX1 cause monogenic and complex forms of lupus erythematosus [abstract]. Eur J Pediatr. 2008;167(3):365.


Perrino FW, de Silva U, Harvey S, Pryor EE Jr, Cole DW, Hollis T. Cooperative DNA binding and communication across the dimer interface in the TREX2 3 '--> 5 '-exonuclease. J Biol Chem. 2008;283(31):21441-52.


Lehtinen DA, Harvey S, Mulcahy MJ, Hollis T, Perrino FW. The TREX1 double-stranded DNA degradation activity is defective in dominant mutations associated with autoimmune disease. J Biol Chem. 2008;283(46):31649-56.


de Silva U, Choudhury S, Bailey SL, Harvey S, Perrino FW, Hollis T. The crystal structure of TREX1 explains the 3' nucleotide specificity and reveals a polyproline II helix for protein partnering. J Biol Chem. 2007;282(14):10537-43.


Hollis T. Crystallization of protein-DNA complexes. Methods Mol Biol. 2007;363():225-237.


Rice G, Newman WG, Dean J, Patrick T, Parmar R, Flintoff K, Robins P, Harvey S, Hollis T, Perrino FW, et al. Heterozygous mutations in TREX1 cause familial chilblain lupus and dominant Aicardi-Goutieres syndrome. Am J Hum Genet. 2007;80(4):811-815.


Lee-Kirsch MA, Chowdhury D, Harvey S, Gong M, Senenko L, Engel K, Pfeiffer C, Hollis T, Gahr M, Perrino FW, et al. A mutation in TREX1 that impairs susceptibility to granzyme A-mediated cell death underlies familial chilblain lupus. J Mol Med. 2007;85(5):531-537.


Herrin A, Hollis T, Eichman BF. Structural basis for 3-methyladenine recognition and removal by a highly-specific DNA glycosylase: the crystal structure of TAG in complex with DNA [abstract]. J Biomol Struct Dyn. 2007;24(6):614.


Metz AH, Hollis T, Eichman BF. DNA damage recognition and repair by 3-methyladenine DNA glycosylase I (TAG). EMBO J. 2007;26(9):2411-2420.


Salsbury FR Jr, Clodfelter JE, Gentry MB, Hollis T, Scarpinato KD. The molecular mechanism of DNA damage recognition by MutS homologs and its consequences for cell death response. Nucleic Acids Res. 2006;34(8):2173-2185.


The maintenance of DNA integrity is essential for normal cellular function and for the propagation of the genetic code to successive generations.  A variety of endogenous cellular reagents and exogenous toxins are capable of reacting with and modifying DNA.  These modifications can pose blocks to replicative DNA polymerases and/or interfere with the binding of regulatory proteins to DNA causing wide spread cellular responses.  Repair of lesions in DNA is a critical cellular response mediated by enzymes that can accurately detect, remove and/or correct the damaged bases.

Research in my laboratory focuses on the structural biology of proteins involved in DNA repair.  We use a combination of X-ray crystallography, biochemistry and molecular biology to address questions of DNA damage recognition and repair by proteins. 

In collaboration with the Perrino Laboratory we are determining the X-ray crystal structures of the 3’-5’ DNA exonucleases TREX1 and TREX2.  Our goal is to understand how the dimeric structure of these proteins contributes to their substrate specificity and catalytic activity.

Additionally, we are working on determining the structures and functions of proteins involved in the cancer susceptibility syndrome, Fanconi anemia.  This rare disease is a result of the cell’s inability to recognize or repair certain types of DNA damage, particularly interstrand crosslinks.