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Fred W. Perrino, Ph.D.Wake Forest School of Medicine

Fred W. Perrino, Ph.D.


Contact Information

Academic: 336-716-4349 | Department: 336-716-2011


Education & Training

  • B.S., Ohio State University, 1979
  • Ph.D., University of Cincinnati, 1986
  • Fellowship, University of Cincinnati, 1985
  • Fellowship, University of Washington Schoo, 1989


  • New York Academy Of Sciences
  • Am Assn Of Cancer Research
  • Am Soc Of Biochem & Mol Biolog
  • Am Soc of Microbiology
Fred W. Perrino, Ph.D.

Fred W. Perrino, Ph.D.

Professor, Biochemistry

Research Interests

Exodeoxyribonucleases; Phosphoproteins; DNA; Autoimmune Diseases of the Nervous System; Nervous System Malformations
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Contact Information

Academic: 336-716-4349 | Department: 336-716-2011


Recent Publications

DNase-active TREX1 frame-shift mutants induce serologic autoimmunity in mice. Sakai T, Miyazaki T, Shin DM, Kim YS, Qi CF, Fariss R, Munasinghe J, Wang H, Kovalchuk AL, Kothari PH, Fermaintt CS, Atkinson JP, Perrino FW, Yan N, Morse HC III.. J Autoimmun. 2017;81():13-23.

The SAMHD1 dNTP triphosphohydrolase is controlled by a redox switch. Mauney CH, Rogers LC, Harris RS, Daniel LW, Devarie-Baez NO, Wu H, Furdui CM, Poole LB, Perrino FW, Hollis T.. Antioxid Redox Signal. 2017;27(16):1317-1331.

Solid-state nanopore analysis of diverse DNA base modifications using a modular enzymatic labeling process. Wang F, Zahid OK, Swain BE, Parsonage D, Hollis T, Harvey S, Perrino FW, Kohli RM, Taylor EW, Hall AR.. Nano Lett. 2017;17(11):7110-7116.

The exonuclease Trex2 shapes psoriatic phenotype. Manils J, Eduard C, Vina-Vilaseca A, Lopez-Cano M, Diez-Villanueva A, Gomez D, Marruecos L, Ferran M, Benito C, Perrino FW, Vavouri T, Maria de Anta J, Ciruela F, Soler C.. J Invest Dermatol. 2016;136(12):2345-2355.

The TREX1 pathway in autoimmune disease [abstract]. Perrino FW.. Environ Mol Mutagen. 2016;57(Suppl 1):S56.

Crystal structure of RNA-DNA duplex provides insight into conformational changes induced by RNase H binding. Davis RR, Shaban NM, Perrino FW, Hollis T.. Cell Cycle. 2015;14(4):668-673.

The multidimensional nature of antiviral innate immunity. Harris RS, Perrino FW, Shaban NM.. Cell Host Microbe. 2015;17(4):423-425.

Exonuclease TREX1 degrades double-stranded DNA to prevent spontaneous lupus-like inflammatory disease. Grieves JL, Fye JM, Harvey S, Grayson JM, Hollis T, Perrino FW.. Proc Natl Acad Sci U S A. 2015;112(16):5117-5122.

Multifaceted role of TREX2 in the skin defense against UV-induced skin carcinogenesis. Manils J, Gomez D, Salla-Martret M, Fischer H, Fye JM, Marzo E, Marruecos L, Serrano I, Salgado R, Rodrigo JP, Garcia-Pedrero JM, Serafin AM, Canas X, Benito C, Toll A, Forcales SV, Perrino FW, Eckhart L, Soler C.. Oncotarget. 2015;6(26):22375-96.

The Arg-62 residues of the TREX1 exonuclease act across the dimer interface contributing to catalysis in the opposing protomers. Fye JM, Coffin SR, Orebaugh CD, Hollis T, Perrino FW.. J Biol Chem. 2014;289(16):11556-65.

Synonymous mutations in RNASEH2A create cryptic splice sites impairing RNase H2 enzyme function in Aicardi-Goutieres syndrome. Rice GI, Reijns MA, Coffin SR, Forte GM, Anderson BH, Szynkiewicz M, Gornall H, Gent D, Leitch A, Botella MP, Fazzi E, Gener B, Lagae L, Olivieri I, Orcesi S, Swoboda KJ, Perrino FW, Jackson AP, Crow YJ.. Hum Mutat. 2013;34(8):1066-1070.

The TREX1 C-terminal region controls cellular localization through ubiquitination. Orebaugh CD, Fye JM, Harvey S, Hollis T, Wilkinson JC, Perrino FW.. J Biol Chem. 2013;288(40):28881-92.

Defects in DNA degradation revealed in crystal structures of TREX1 exonuclease mutations linked to autoimmune disease. Bailey SL, Harvey S, Perrino FW, Hollis T.. DNA Repair. 2012;11(1):65-73.

Bypass of N2-ethylguanine by human DNA polymerase kappa. Pence MG, Blans P, Zink CN, Fishbein JC, Perrino FW.. DNA Repair. 2011;10(1):56-64.

Evaluation of the TREX1 gene in a large multi-ancestral lupus cohort. Namjou B, Kothari PH, Kelly JA, Glenn SB, Ojwang JO, Adler A, Alarcon-Riquelme ME, Perrino FW, Freedman BI, Langefeld CD, et al.. Genes Immun. 2011;12(4):270-279.

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

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

The TREX1 exonuclease R114H mutation in Aicardi-Goutieres syndrome and lupus reveals dimeric structure requirements for DNA degradation activity. Orebaugh CD, Fye JM, Harvey S, Hollis T, Perrino FW.. J Biol Chem. 2011;286(46):40246-54.

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

The structure of the mammalian RNase H2 complex provides insight into RNA.NA hybrid processing to prevent immune dysfunction. Shaban NM, Harvey S, Perrino FW, Hollis T.. J Biol Chem. 2010;285(6):3617-3624.

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

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

A DNA polymerase-alpha.primase cofactor with homology to replication protein A-32 regulates DNA replication in mammalian cells. Casteel DE, Zhuang S, Zeng Y, Perrino FW, Boss GR, Goulian M, Pilz RB.. J Biol Chem. 2009;284(9):5807-5818.

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

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

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

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

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

WRN exonuclease activity is blocked by DNA termini harboring 3 degree obstructive groups. Harrigan JA, Fan J, Momand J, Perrino FW, Bohr VA, Wilson DM III.. Mech Ageing Dev. 2007;128(3):259-266.

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

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

Mutations in the gene encoding the 3 '-5 ' DNA exonuclease TREX1 are associated with systemic lupus erythematosus. Lee-Kirsch MA, Gong M, Chowdhury D, Seneko L, Engel K, Lee Y-A, de Silva U, Bailey SL, Harvey S, Perrino FW, et al.. Nat Genet. 2007;39(9):1065-1067.

Mutagenesis by exocyclic alkylamino purine adducts in Escherichia coli. Upton DC, Wang X, Blans P, Perrino FW, Fishbein JC, Akman SA.. Mutat Res. 2006;599(1-2):1-10.

Replication of N(2)-ethyldeoxyguanosine DNA adducts in the human embryonic kidney cell line 293. Upton DC, Wang X, Blans P, Perrino FW, Fishbein JC, Akman SA.. Chem Res Toxicol. 2006;19(7):960-967.

The exonuclease TREX1 is in the SET complex and acts in concert with NM23-H1 to degrade DNA during granzyme A-mediated cell death. Chowdhury D, Beresford PJ, Zhu P, Zhang D, Sund J-S, Demple B, Perrino FW, Lieberman J.. Mol Cell. 2006;23(1):133-142.

Structure of the Escherichia coli DNA polymerase III epsilon-HOT proofreading complex. Kirby TW, Harvey S, DeRose EF, Chalov S, Chikova AK, Perrino FW, Schaaper RM, London RE, Pedersen LC.. J Biol Chem. 2006;281(50):38466-71.

All Publications

For a listing of recent publications, refer to PubMed, a service provided by the National Library of Medicine.

For a list of earlier publications, visit the Carpenter Library Publication Search.

Professor, Biochemistry

Fred W. Perrino, Ph.D.

Fred W. Perrino, Ph.D.

Professor, Biochemistry

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