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Molecular and Cellular Biosciences at Wake Forest University

Wake Forest University Graduate School » Molecular and Cellular Biosciences

Fred W Perrino, Ph.D.

Fred W Perrino, Ph.D.
Education & Training
  BS Ohio State University 1979
  PhD University of Cincinnati 1986
  University of Cincinnati 1985
    University of Washington School of Medicine 1989
New York Academy of Sciences
American Association of Cancer Research
American Society of Biochem & Molecular Biology
American Society of Microbiology


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. Synonymous mutations in RNASEH2A create cryptic splice sites impairing RNase H2 enzyme function in Aicardi-Goutieres syndrome. Hum Mutat. 2013;34(8):1066-1070.



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


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


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.



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.


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.


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


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.


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


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.


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. Mutations in the gene encoding the 3 '-5 ' DNA exonuclease TREX1 are associated with systemic lupus erythematosus. Nat Genet. 2007;39(9):1065-1067.


Biochemistry of DNA and RNA in human disease

One of the hallmarks of the autoimmune disease Lupus is the development of an immune reaction that producesautoantibodies to ones own DNA. Although the source of this DNA has not been firmly established, it is known that in adults about one hundred billion cells undergo normal cell death processes each day. As part of this normal process these dying cells must disassemble the 2.9 billion basepairs of DNA that comprise the human genome present in each and every cell. Work in the Perrino laboratory resulted in the discovery of the TREX1 gene that encodes a powerful DNA disassembly enzyme that appears to be responsible, in part, for this DNA removal process. When the TREX1 enzyme does not function properly the DNA from dying cells persists and an inappropriate immune response is initiated. The effects of this immune response vary in autoimmune patients but the failure of TREX1 to eliminate DNA from dying cells might be at the root cause of the aberrant immune reaction in some lupus patients. Studies in the lab are focused on how TREX1 enzyme dysfunction leads to the development of Lupus and related autoimmune disorders.

The Perrino laboratory is collaborating with theHollis laboratory to examine structure, mechanism, and function of the enzymes that cause a spectrum of human autoimmune diseases including Lupus, Aicardi-Goutieres Syndrome, Familial Chilblain Lupus, and Retinal Vasculopathy and Cerebral Leukodystrophy. Our studies are directed at unraveling the mechanistic details of the TREX1 and RNase H2 enzymes to better understand the molecular actions of these DNA and RNA processing enzymes and the pathways through which mutations in these enzymes lead to autoimmune disease.

The human genome is susceptible to damage by many chemicals produced naturally in cells or by environmental exposure. The biological consequence of this damage is relevant to mutagenesis, to carcinogenesis, and to cancer therapeutics. Despite our recognition of DNA damage as a path to mutagenesis our knowledge concerning the response of the human DNA polymerases and nucleases to the damage inflicted on DNA is limited. Additional studies in the laboratory on TREX2 and the lesion bypass DNA polymerases are directed at understanding how damaged DNA is processed to prevent mutation and cancer.