Nancy L Sawtell , PhD

My PhD and postdoctoral training encompassed pathology, immunology, developmental biology and virology.  During these training years and as a student of pathology, I developed a comprehensive knowledge of disease processes in the context of the whole organism.   Developing and utilizing animal models of human disease has been at the core of my research. The past 21 years, my research has focused on the molecular mechanisms underlying HSV latency and reactivation, viral processes central to the human disease caused by this virus.  Our research efforts have included the development of novel in vivo approaches to examine rare events that occur in the context of an extensive and diverse cellular background.  These rare events, however, are the underpinnings of chronic inflammation and serious disease outcomes. The ability to quantify these events at the single neuron level has resulted in fundamental new insights into HSV pathogenesis in vivo. Recently, we have made observations which shifts the HSV reactivation paradigm,  identifying an essential role for the viral protein VP16 in the earliest stages of HSV reactivation in neurons in vivo. We have also identified novel regulation of VP16 in neurons, which uncouples VP16 expression as a virally regulated “late gene” in the ongoing lytic cycle and places it under the control of the neuron, thus the VP16 promoter becomes the cell state sensor and VP16, the effector.

PhD: University of Cincinnati College of Medicine Cincinnati, Ohio, 1986 ( Pathology/Immunology)

BA: Case Western Reserve University Cleveland, Oh, 1975 (Chemistry)

Grant: #1 R21 AI116389 Investigators:Sawtell, Nancy; Thompson, Richard 01-01-2015 -12-31-2016 National Institute of Allergy and Infectious Diseases Revealing networks targeted by HSV-1 ncRNAs with in vivo gain-of-function studies Role:Collaborator $250,289.00 Awarded Level:Federal

Grant: #CUMC (R01AG083963) Investigators:Sawtell, Nancy; Thompson, Richard 08-15-2023 -04-30-2028 Columbia University Investigating the role of long-term latent herpes simplex virus infection on ApoE4 - associated Alzheimer's disease pathogenesis Role:PI 22612.00 Hold Level:Higher Education

Peer Reviewed Publications

Divanovic, Senad; Sawtell, Nancy M; Trompette, Aurelien; Warning, Jamie I; Dias, Alexandra; Cooper, Andrea M; Yap, George S; Arditi, Moshe; Shimada, Kenichi; Duhadaway, James B; Prendergast, George C; Basaraba, Randall J; Mellor, Andrew L; Munn, David H; Aliberti, Julio; Karp, Christopher L (2012. ) Opposing biological functions of tryptophan catabolizing enzymes during intracellular infection.The Journal of infectious diseases, , 205 (1 ) ,152-61 More Information

Catez, Frédéric; Picard, Christel; Held, Kathrin; Gross, Sylvain; Rousseau, Antoine; Theil, Diethilde; Sawtell, Nancy; Labetoulle, Marc; Lomonte, Patrick (2012. ) HSV-1 genome subnuclear positioning and associations with host-cell PML-NBs and centromeres regulate LAT locus transcription during latency in neurons.PLoS pathogens, , 8 (8 ) ,e1002852 More Information

Thompson, Richard L; Sawtell, Nancy M (2011. ) The herpes simplex virus type 1 latency associated transcript locus is required for the maintenance of reactivation competent latent infections.Journal of neurovirology, , 17 (6 ) ,552-8 More Information

Sawtell, Nancy M; Triezenberg, Steven J; Thompson, Richard L (2011. ) VP16 serine 375 is a critical determinant of herpes simplex virus exit from latency in vivo.Journal of neurovirology, , 17 (6 ) ,546-51 More Information

Thompson, Richard L; Sawtell, Nancy M (2010. ) Therapeutic implications of new insights into the critical role of VP16 in initiating the earliest stages of HSV reactivation from latency.Future medicinal chemistry, , 2 (7 ) ,1099-105 More Information

Farley, Nicholas; Bernstein, David I; Bravo, Fernando J; Earwood, Julie; Sawtell, Nancy; Cardin, Rhonda D (2010. ) Recurrent vaginal shedding of herpes simplex type 2 virus in the mouse and effects of antiviral therapy.Antiviral research, , 86 (2 ) ,188-95 More Information

Thompson, Richard L; Preston, Chris M; Sawtell, Nancy M (2009. ) De novo synthesis of VP16 coordinates the exit from HSV latency in vivo.PLoS pathogens, , 5 (3 ) ,e1000352 More Information

Currier, Mark A; Gillespie, Rebecca A; Sawtell, Nancy M; Mahller, Yonatan Y; Stroup, Greg; Collins, Margaret H; Kambara, Hirokazu; Chiocca, E Antonio; Cripe, Timothy P (2008. ) Efficacy and safety of the oncolytic herpes simplex virus rRp450 alone and combined with cyclophosphamide.Molecular therapy : the journal of the American Society of Gene Therapy, , 16 (5 ) ,879-85 More Information

Sawtell, Nancy M (2005. ) Detection and quantification of the rare latently infected cell undergoing herpes simplex virus transcriptional activation in the nervous system in vivo. Methods in molecular biology (Clifton, N.J.), , 292 ,57-72

Thompson, R L; Sawtell, N M (2006. ) Evidence that the herpes simplex virus type 1 ICP0 protein does not initiate reactivation from latency in vivo.Journal of virology, , 80 (22 ) ,10919-30 More Information

Sawtell, N M; Thompson, R L; Haas, R L (2006. ) Herpes simplex virus DNA synthesis is not a decisive regulatory event in the initiation of lytic viral protein expression in neurons in vivo during primary infection or reactivation from latency.Journal of virology, , 80 (1 ) ,38-50 More Information

Sawtell, N M; Thompson, R L (2004. ) Comparison of herpes simplex virus reactivation in ganglia in vivo and in explants demonstrates quantitative and qualitative differences.Journal of virology, , 78 (14 ) ,7784-94 More Information

Thompson, R L; Shieh, May T; Sawtell, N M (2003. ) Analysis of herpes simplex virus ICP0 promoter function in sensory neurons during acute infection, establishment of latency, and reactivation in vivo. Journal of virology, , 77 (22 ) ,12319-30

Sawtell, N M (2003. ) Quantitative analysis of herpes simplex virus reactivation in vivo demonstrates that reactivation in the nervous system is not inhibited at early times postinoculation. Journal of virology, , 77 (7 ) ,4127-38

Sawtell, N M (2002. ) Preparation of single cells from solid tissues for analysis by PCR.Current protocols in molecular biology / edited by Frederick M. Ausubel ... [et al.], , Chapter 25 ,Unit 25A.2 More Information

Sawtell, N M; Thompson, R L; Stanberry, L R; Bernstein, D I (2001. ) Early intervention with high-dose acyclovir treatment during primary herpes simplex virus infection reduces latency and subsequent reactivation in the nervous system in vivo.The Journal of infectious diseases, , 184 (8 ) ,964-71 More Information

Thompson, R L; Sawtell, N M (2001. ) Herpes simplex virus type 1 latency-associated transcript gene promotes neuronal survival.Journal of virology, , 75 (14 ) ,6660-75 More Information

Thompson, R L; Sawtell, N M (2000. ) HSV latency-associated transcript and neuronal apoptosis. Science (New York, N.Y.), , 289 (5485 ) ,1651

Thompson, R L; Sawtell, N M (2000. ) Replication of herpes simplex virus type 1 within trigeminal ganglia is required for high frequency but not high viral genome copy number latency. Journal of virology, , 74 (2 ) ,965-74

Sawtell, N M; Bernstein, D I; Stanberry, L R (1999. ) A temporal analysis of acyclovir inhibition of induced herpes simplex virus type 1 In vivo reactivation in the mouse trigeminal ganglia.The Journal of infectious diseases, , 180 (3 ) ,821-3 More Information

Efstathiou, S; Field, H J; Griffiths, P D; Kern, E R; Sacks, S L; Sawtell, N M; Stanberry, L R (1999. ) Herpes simplex virus latency and nucleoside analogues. Antiviral research, , 41 (3 ) ,85-100

Sawtell, N M (1998. ) The probability of in vivo reactivation of herpes simplex virus type 1 increases with the number of latently infected neurons in the ganglia. Journal of virology, , 72 (8 ) ,6888-92

Sawtell, N M; Poon, D K; Tansky, C S; Thompson, R L (1998. ) The latent herpes simplex virus type 1 genome copy number in individual neurons is virus strain specific and correlates with reactivation. Journal of virology, , 72 (7 ) ,5343-50

Thompson, R L; Sawtell, N M (1997. ) The herpes simplex virus type 1 latency-associated transcript gene regulates the establishment of latency. Journal of virology, , 71 (7 ) ,5432-40

Sawtell, N M (1997. ) Comprehensive quantification of herpes simplex virus latency at the single-cell level. Journal of virology, , 71 (7 ) ,5423-31

Perng, G C; Chokephaibulkit, K; Thompson, R L; Sawtell, N M; Slanina, S M; Ghiasi, H; Nesburn, A B; Wechsler, S L (1996. ) The region of the herpes simplex virus type 1 LAT gene that is colinear with the ICP34.5 gene is not involved in spontaneous reactivation. Journal of virology, , 70 (1 ) ,282-91

Perng, G C; Thompson, R L; Sawtell, N M; Taylor, W E; Slanina, S M; Ghiasi, H; Kaiwar, R; Nesburn, A B; Wechsler, S L (1995. ) An avirulent ICP34.5 deletion mutant of herpes simplex virus type 1 is capable of in vivo spontaneous reactivation. Journal of virology, , 69 (5 ) ,3033-41

Bolovan, C A; Sawtell, N M; Thompson, R L (1994. ) ICP34.5 mutants of herpes simplex virus type 1 strain 17syn+ are attenuated for neurovirulence in mice and for replication in confluent primary mouse embryo cell cultures. Journal of virology, , 68 (1 ) ,48-55

Pyles, R B; Sawtell, N M; Thompson, R L (1992. ) Herpes simplex virus type 1 dUTPase mutants are attenuated for neurovirulence, neuroinvasiveness, and reactivation from latency. Journal of virology, , 66 (11 ) ,6706-13

Sawtell, N M; Thompson, R L (1992. ) Herpes simplex virus type 1 latency-associated transcription unit promotes anatomical site-dependent establishment and reactivation from latency. Journal of virology, , 66 (4 ) ,2157-69

Sawtell, N M; Thompson, R L (1992. ) Rapid in vivo reactivation of herpes simplex virus in latently infected murine ganglionic neurons after transient hyperthermia. Journal of virology, , 66 (4 ) ,2150-6

Sawtell, N M; Hartman, A L; Lessard, J L (1990. ) Conserved tissue-restricted expression of HUC 1-1 actin phenotype among eumetazoan organisms.The Journal of experimental zoology, , 256 (1 ) ,54-62 More Information

Rudnicki, M A; Sawtell, N M; Reuhl, K R; Berg, R; Craig, J C; Jardine, K; Lessard, J L; McBurney, M W (1990. ) Smooth muscle actin expression during P19 embryonal carcinoma differentiation in cell culture.Journal of cellular physiology, , 142 (1 ) ,89-98 More Information

Sawtell, N M; Lessard, J L (1989. ) Cellular distribution of smooth muscle actins during mammalian embryogenesis: expression of the alpha-vascular but not the gamma-enteric isoform in differentiating striated myocytes. The Journal of cell biology, , 109 (6 Pt 1 ) ,2929-37

Hartman, A L; Sawtell, N M; Lessard, J L (1989. ) Expression of actin isoforms in developing rat intestinal epithelium. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society, , 37 (8 ) ,1225-33

Sawtell, N M; Hartman, A L; Weiss, M A; Pesce, A J; Michael, J G (1988. ) C3 dependent, C5 independent immune complex glomerulopathy in the mouse. Laboratory investigation; a journal of technical methods and pathology, , 58 (3 ) ,287-93

Sawtell, N M; Hartman, A L; Lessard, J L (1988. ) Unique isoactins in the brush border of rat intestinal epithelial cells.Cell motility and the cytoskeleton, , 11 (4 ) ,318-25 More Information

Sawtell, N M; Weiss, M A; Pesce, A J; Michael, J G (1987. ) An immune complex glomerulopathy associated with glomerular capillary thrombosis in the laboratory mouse. A highly reproducible accelerated model utilizing cationized antigen. Laboratory investigation; a journal of technical methods and pathology, , 56 (3 ) ,256-63

Sawtell, N M; DiPersio, L; Michael, J G; Pesce, A J; Weiss, M A (1984. ) Expression of normal and tumor-associated antigens in human breast carcinoma. Laboratory investigation; a journal of technical methods and pathology, , 51 (2 ) ,225-32

Sawtell, Nancy M; Thompson, Richard L (2020. ) Alphaherpesvirus Latency and Reactivation with a Focus on Herpes Simplex Virus.Current issues in molecular biology, , 41 ,267-356 More Information

Doll, Jessica R; Hoebe, Kasper; Thompson, Richard L; Sawtell, Nancy M (2020. ) Resolution of herpes simplex virus reactivation in vivo results in neuronal destruction.PLoS pathogens, , 16 (3 ) ,e1008296 More Information

Sawtell, Nancy M; Thompson, Richard L (2020. ) HSV Mutant Generation and Dual Detection Methods for Gaining Insight into Latent/Lytic Cycles In Vivo.Methods in molecular biology (Clifton, N.J.), , 2060 ,219-239 More Information

Thompson, Richard L; Sawtell, Nancy M (2019. ) Targeted Promoter Replacement Reveals That Herpes Simplex Virus Type-1 and 2 Specific VP16 Promoters Direct Distinct Rates of Entry Into the Lytic Program in Sensory Neurons in vivo.Frontiers in microbiology, , 10 ,1624 More Information

Doll, Jessica R; Thompson, Richard L; Sawtell, Nancy M (2019. ) Infectious Herpes Simplex Virus in the Brain Stem Is Correlated with Reactivation in the Trigeminal Ganglia.Journal of virology, , 93 (8 ) , More Information

Pandey, Utsav; Renner, Daniel W; Thompson, Richard L; Szpara, Moriah L; Sawtell, Nancy M (2017. ) Inferred father-to-son transmission of herpes simplex virus results in near-perfect preservation of viral genome identity and in vivo phenotypes.Scientific reports, , 7 (1 ) ,13666 More Information

Doll, Jessica R; Sawtell, Nancy M (2017. ) Analysis of Herpes Simplex Virus Reactivation in Explant Reveals a Method-Dependent Difference in Measured Timing of Reactivation.Journal of virology, , 91 (16 ) , More Information

Sawtell, Nancy M; Thompson, Richard L (2016. ) De Novo Herpes Simplex Virus VP16 Expression Gates a Dynamic Programmatic Transition and Sets the Latent/Lytic Balance during Acute Infection in Trigeminal Ganglia.PLoS pathogens, , 12 (9 ) ,e1005877 More Information

Sawtell, Nancy M; Thompson, Richard L (2016. ) Herpes simplex virus and the lexicon of latency and reactivation: a call for defining terms and building an integrated collective framework.F1000Research, , 5 , More Information

Thompson, Richard L; Williams, Robert W; Kotb, Malak; Sawtell, Nancy M (2014. ) A forward phenotypically driven unbiased genetic analysis of host genes that moderate herpes simplex virus virulence and stromal keratitis in mice.PloS one, , 9 (3 ) ,e92342 More Information

Sawtell, Nancy M; Thompson, Richard L (2014. ) Herpes simplex virus mutant generation and dual-detection methods for gaining insight into latent/lytic cycles in vivo.Methods in molecular biology (Clifton, N.J.), , 1144 ,129-47 More Information

Research - Cincinnati Children's Hospital Medical Center
3333 Burnet Ave
Cincinnati  Ohio, 45229-3039
Phone: 513-636-7880
nancy.sawtell@cchmc.org