Kate Excoffon

Department:
Orthopaedic and Plastic Surgery

Education History

  • 2001-2008 Postdoctoral Scholar/Research Scientist, University of Iowa, IA, USA
  • 1995-2000 Ph.D. Genetics, University of British Columbia, BC, Canada
  • 1990-1994 B.Sc. Biochemistry and Genetics, University of Guelph, ON, Canada

Research Statement

Research in the Excoffon laboratory is focused on understanding how cells communicate and what happens when a viral pathogen co-opts cell surface proteins for receptors.

Adenovirus is a common pathogen and, depending on the serotype, may cause a variety of disease symptoms. The receptor for adenovirus is also a receptor for Coxsackie B viruses and is named Coxsackie-Adenovirus Receptor (CAR). CAR normally behaves as a homotypic adhesion protein but several other functions, including intracellular protein trafficking and leukocyte transmigration, have recently been discovered.

I will be focusing on 3 related areas: virus-cell interactions (pathogenesis/gene therapy), cell-cell interactions (epithelia and lymphocytes), and the endogenous function of the Coxsackie-Adenovirus Receptor (CAR) on the molecular level (primarily protein-protein interactions). Gene therapy work will also include adeno-associated virus.

Publications

Kemp, MG, Krishnamurthy, S, Kent, MN, Schumacher, DL, Sharma, P, Excoffon, KJ, and Travers, JB. Spironolactone depletes the XPB protein and inhibits DNA damage responses in UVB-irradiated human skin. Journal of Investigative Dermatology. 2018 Sep 15. pii: S0022-202X(18)32568-5. PMID: 30227140

Wooley, DP, Sharma, P, Weinstein, JR, Narayan, PKL, Schaffer, DV, and Excoffon, KJ. (2017) A directed evolution approach to select for novel Adeno-associated virus capsids on an HIV-1 producer T cell line. Journal of Virological Methods. J Virol Methods. 2017 Dec; 250:47-54. PMID: 28918073

Bowers, JR, Readler, JM, Sharma, P, and Excoffon, KJ. (2017) Poliovirus Receptor: More than a simple viral receptor. Virus Research. October 15 242:1-6. PMID: 28870470 

Sharma, P., Martis, P., and Excoffon, KJ. (2017) Adenovirus transduction: More complicated than receptor expression. Virology. 502: 144-151. PMID: 28049062

Sharma P, Wimalawansa SM, Gould GC, Johnson RM, Excoffon KJ. (2016) Adeno-Associated Virus 5 Transduces Adipose-Derived Stem Cells with Greater Efficacy Than Other Adeno-Associated Viral Serotypes. Human Gene Therapy Methods. 27(6):219-227. PMID: 27820963

Steines, B., Dickey, DD., Bergen, J., Excoffon, KJ., Weinstein, J., Li, X., Yan, Ziying., Abou Alaiwa, M., Shah, VS., Bouzek, DC., Powers, LS., Gansemer, ND., Ostedgaard, LS., Engelhardt, JF., Stoltz, DA., Welsh, MJ., Sinn, PL., Schaffer, DV., and Zabner, J. (2016) CFTR gene transfer with AAV improves early cystic fibrosis pig phenotypes. Journal of Clinical Investigations Insight. 1(14):e88728. PMID 27699238.

Kotha PNL, Sharma P, Kolawole AO, Yan R, Alghamri MS, Brockman TL, Gomez-Cambronero J, and Excoffon KJ. (2015) Adenovirus Entry from the Apical Surface of Polarized Epithelia is Facilitated by the Host Innate Immune Response. PLoS Pathogens. 11(3): e1004696. PMID 25768646.

Yan R, Sharma P, Kolawole AO, Martin S, Readler J, Kotha PNL, Hostetler HA, and Excoffon KJ. (2015) The PDZ3 domain of the cellular scaffolding protein MAGI-1 interacts with the coxsackievirus and adenovirus receptor (CAR). The International Journal of Biochemistry & Cell Biology. 61:29-34. PMID 25622559.

Excoffon, KJ, Bowers, JB, and Sharma, P. (2014) Alternative Splicing of Viral Receptors: A Review of the Diverse Morphologies and Physiologies of Adenoviral Receptors. Recent Research Developments in Virology. 9:1-24. PMID: 649430

Excoffon KJ, Kolawole AO, Kusama N, Gansemer ND, Sharma P, Hruska-Hageman AM, Petroff E, Benson CJ. (2012) Coxsackievirus and adenovirus receptor (CAR) mediates trafficking of acid-sensing ion channel 3 (ASIC3) via PSD-95. Biochemical and Biophysical Research Communications. 2012 Aug; 425:13-18.  PMID: 22809504.

Kolawole AO, Sharma P, Yan R, Lewis KJ, Hostetler HA, Ashbourne Excoffon KJ. (2012) The PDZ1 and PDZ3 Domains of MAGI-1 Regulate the Eight Exon Isoform of the Coxsackievirus and Adenovirus Receptor. Journal of Virology. Sept; 86(17):9244-54. PMID: 22718816.

Dickey DD, Excoffon KJ, Young KR, Parekh KR, Zabner J. (2012) Hoechst increases adeno-associated virus-mediated transgene expression in airway epithelia by inducing the cytomegalovirus promoter. Journal of Gene Medicine. Jun; 14(6):366-73. doi: 10.1002/jgm.2632. PMID: 22610695.

Sharma P, Kolawole AO, Wiltshire SM, Frondorf K, Excoffon KJ. (2012) Accessibility of the Coxsackievirus and adenovirus receptor (CAR) and its importance in adenovirus gene transduction efficiency. Journal of General Virology. Jan; 93(Pt 1):155-8. Epub 2011 Sep 14. PMID: 21918008.

Dickey DD, Excoffon KJ, Koerber JT, Bergen J, Steines B, Klesney-Tait J, Schaffer DV, Zabner J. (2011) Enhanced sialic acid-dependent endocytosis explains the increased airway epithelia infection efficiency of a novel adeno-associated virus. Journal of Virology. Sep; 85(17):9023-30. PMID: 21697483.

Aoki K, Benkö M, Davison AJ, Echavarria M, Erdman DD, Harrach B, Kajon AE, Schnurr D, Wadell G; Members of the Adenovirus Research Community. (2011) Toward an integrated human adenovirus designation system that utilizes molecular and serological data and serves both clinical and fundamental virology. Journal of Virology. Jun; 85(11):5703-4. PMID: 21450837.

Excoffon KJDA, Gansemer ND, Mobily ME, Karp PH, Parekh KR, Zabner J. (2010) Isoform-specific regulation and localization of the Coxsackie and adenovirus receptor in human airway epithelia. PLoS One. Mar; 26;5(3):e9909. PMID: 2845650.

Granio O, Ashbourne Excoffon KJ, Henning P, Melin P, Norez C, Gonzalez G, Karp PH, Magnusson MK, Habib N, Lindholm L, Becq F, Boulanger P, Zabner J, Hong SS. (2010) Adenovirus 5-fiber 35 chimeric vector mediates efficient apical correction of the cystic fibrosis transmembrane conductance regulator defect in cystic fibrosis primary airway epithelia. Human Gene Therapy. Mar; 21(3):251-69. PMID: 19788389.

Excoffon K.J.D.A., Koerber, J.T., Dickey, D.D., Murtha, M., Keshavjee, S., Kaspar, B., Zabner, J. and Schaffer, D.V. (2009) Directed evolution of adeno-associated virus to an infectious respiratory virus. Proceedings of the National Academy of Science USA. Mar 10;106(10):3865-70. PMID: 19237554.

Excoffon K.J.D.A., Guglielmi, K.M., Wetzel, J.D., Gansmer, N, Campbell, J.A., Dermody, T.S. and Zabner, J. (2008) Reovirus preferentially infects the basolateral surface and is released from the apical surface of polarized human respiratory epithelial cells. Journal of Infectious Diseases 197(8):1189-97. PMID: 18419529. (Cover image)

Granio, O., Norez, C., Excoffon, K.J.D.A., Karp, P.H., Lusky, M., Becq, F., Boulanger, B., Zabner, J. and Hong, S.S. (2007) Cellular localization and Cl- channel activity of GFP-CFTR in airway epithelial and tracheal cells. American Journal of Respiratory Care and Critical Medicine 37(6):631-9. PMID: 17641299.

Humlicek, A.L. Manzel, L.J., Chin, C.L., Shi, L, Excoffon, K.J.D.A., Winter, M.C., Shasby, D.M., and Look, D.C. (2007) Paracellular permeability restricts airway epithelial responses to selectively allow activation by mediators at the basolateral surface. Journal of Immunology 178(10):6395-403. PMID: 17475869.

Excoffon, K.J.D.A., Gansemer, N, Traver, G.L. and Zabner, J. (2007) Functional effects of Coxsackievirus and adenovirus receptor glycosylation on homophilic adhesion and adenoviral infection. Journal of Virology 81(11):5573-8. Epub 2007 Mar 21. PMID: 17376928.

Moskwa, P., Lorentzen, D., Excoffon, K.J., Zabner, J., McCray Jr, PB., Nauseef, WM., Dupuy, C., Banfi, B. (2006) A novel host defense system of airways is defective in cystic fibrosis. American Journal of Respiratory Care and Critical Medicine. 175(2):174-83. PMID: 17082494.

Excoffon, K.J.D.A., Avenarius, M.R., Hansen, M.R., Kimberling, W.J., Najmabadi, H., Smith, R.J., Zabner, J. (2006) The coxsackievirus and adenovirus receptor: A new adhesion protein in cochlear development. Hearing Research. 215(1-2):1-9. PMID: 16678988 (Cover Image)

Ross CJ, Liu G, Kuivenhoven JA, Twisk J, Rip J, van Dop W, Ashbourne Excoffon KJ, Lewis SM, Kastelein JJ, Hayden MR.  (2005) Complete rescue of Lipoprotein Lipase-deficient mice by somatic gene transfer of the naturally occurring LPLS447X beneficial mutation. Arteriosclerosis, Thrombosis and Vascular Biology. 25(10):2143-50. PMID: 16002740.

Excoffon, K.J.D.A., Traver, G, and Zabner, J. (2005) The role of the extracellular domain in the biology of the Coxsackievirus and Adenovirus Receptor. American Journal of Respiratory Cell and Molecular Biology. 32(6):498-503. PMID: 15778494.

Davis, B., Nguyen, J., Stoltz, D., Depping, D., Excoffon, K.J.D. and Zabner, J. (2004) Adenovirus-mediated gene transfer to airway epithelia is enhanced by apical localization of the Coxsackie-Adenovirus Receptor by GPI In VivoMolecular Therapy. 10(3):500-6. PMID: 15336650.

Excoffon, K.J.D.A., Hruska-Hageman, A., Klotz, M., Traver, G. and Zabner, J. (2004) A role for the PDZ binding domain of the Coxsackie B virus and Adenovirus Receptor (CAR) in cell adhesion and growth. Journal of Cell Science, 117(Pt 19):4401-9. PMID: 15304526.

Zabner J, Winter M, Excoffon KJ, Stoltz D, Ries D, Shasby S, Shasby M. (2003) Histamine alters E-cadherin cell adhesion to increase human airway epithelial permeability. Journal of Applied Physiology, 95(1):394-401. PMID: 12794099.

Ostedgaard LS, Randak C, Rokhlina T, Karp P, Vermeer D, Ashbourne Excoffon KJ, Welsh MJ. (2003) Effects of C-terminal deletions on cystic fibrosis transmembrane conductance regulator function in cystic fibrosis airway epithelia. Proceedings of the National Academy of Science, USA. 100(4):1937-42. PMID: 12578973.

Excoffon, K.J.D.A., Moninger, T. and Zabner, J. (2003) The Coxsackie B Virus and Adenovirus Receptor Resides in a Distinct Membrane Microdomain, Journal of Virology, 77(4):2559-67. PMID: 12551994.

Backus R.C., Ginzinger D.G., Ashbourne Excoffon K.J., Clee S.M., Hayden M.R., Eckel R.H., Hickman M.A. and Rogers Q.R. (2001) Maternal expression of functional lipoprotein lipase and effects on body fat mass and body condition scores of mature cats with lipoprotein lipase deficiency American Journal of Veterinary Research, 62(2):264-269. PMID: 11212037.

Liu G., Ashbourne Excoffon K.J., Wilson J.E., McManus B.M., Rogers Q.R., Miao L., Kastelein J.J., Lewis M.E. and Hayden M.R. (2000) Phenotypic correction of feline lipoprotein lipase deficiency by adenoviral gene transfer. Human Gene Therapy, 11(1):21-32. PMID: 10646636.

Brooks-Wilson A., Marcil M., Clee S.M., Zhang L.H., Roomp K., van Dam M., Yu L., Brewer C., Collins J.A., Molhuizen H.O., Loubser O., Ouelette B.F., Fichter K., Ashbourne-Excoffon K.J., Sensen C.W., Scherer S., Mott S., Denis M., Martindale D., Frohlich J., Morgan K., Koop B., Pimstone S., Kastelein J.J., Genest, J. and Hayden M.R. (1999) Mutations in ABC1 in Tangier disease and familial high-density lipoprotein deficiency. Nature Genetics, 22(4):336-345. PMID: 10431236.

Liu, G., Excoffon, K.J.D.A., Wilson, J., McManus, B., Miao, L., Benoit, P., Duverger, N., Branellec, D., Denefle, P.P., Jones, B., Hayden, M.R. and Lewis, M.E.S. (1998) Enhanced lipolysis in normal mice expressing liver-derived human lipoprotein lipase after adenoviral gene transfer. Clinical Investigations in Medicine, 21(4-5):172-185. PMID: 9800066.

Ashbourne Excoffon, K.J., Liu, G., Miao, L., Wilson, J.E., McManus, B.M., Semenkovich, C.F., Coleman, T., Benoit, P., Duberger, N., Branellec, D., Denefle, P., Hayden, M.R. and Lewis, M.E.S. (1997) Correction of Hypertriglyceridemia and Impaired Fat Tolerance in Lipoprotein Lipase Deficient Mice by Adenoviral-Mediated Expression of Human Lipoprotein Lipase. Arteriosclerosis, Thrombosis and Vascular Biology, 17:2532-2539. PMID: 9409224.

Ginzinger, D.G., Wilson, J.E., Redenbach, D., Lewis, M.E.S., Clee, S.M., Excoffon, K.J.D.A., Rogers, Q.R., Hayden, M.R., and McManus, B.M. (1997) Diet-Induced Atherosclerosis in the Domestic Cat. Laboratory Investigations, 77(5):409-419. PMID: 9389784.

Liu, G., Ashbourne Excoffon, K.J., Benoit, P., Ginzinger, D.G.,Miao, L., Ehrenborg, E., Duverger, N., Denefle, P., Hayden, M.R., and Lewis, M.E.S. (1997) Efficient adenoviral-mediated ectopic gene expression of human lipoprotein lipase (LPL) in human hepatic (HepG2) Cells.  Human Gene Therapy, 8:205-214 (1997). PMID: 9017424.

Lewis, M.E.S., Liu, G., Ginzinger, D.G., Benoit, P., Jones, S.D., Ashbourne, K.J., Wilson, J.E., McManus, B.M., Duverger, N., Denefle, P.P. and Hayden, M.R. (1996) Gene-based therapeutic strategies for human lipoprotein lipase (LPL) deficiency:  Rationale and prospects for alteration of atherogenic risk. Transfusion Science, 17(1):79-87.

Sharom, F.J, DiDiodato, G., Yu, X. and Ashbourne, K.J. (1995) Interaction of  the P-glycoprotein multidrug transporter with peptides and ionophores. Journal of Biological Chemistry,270(17):10334-41. PMID: 7730340.

Galatsis, P., Ashbourne, K.J., Manwell, J.J., Wendling, P., Dufault, R., Hatt, K.L., Ferguson, G. and Gallagher, J.F. (1993) Synthesis of Fused ring Cyclobutenones Via A Tandem [2+2] Cycloaddition-Beta-Elimination Sequence. Journal of Organic Chemistry, 58:1491-1495.

Ashbourne, K.J., Byth, B.C., Meijers, J.C.M. and Cox, D.W. (1993) Polymorphism of the Protein C Inhibitor Gene (PCI) on Chromosome 14. Human Molecular Genetics, 2:92. PMID: 8098248.

Professional Affiliations/Memberships

04/2012-present        American Society for Microbiology

12/2009-present        American Association for the Advancement of Science

05/2006-present        American Society for Virology

12/2001-present        American Society of Cell Biology

05/1998-present          American Society of Gene and Cell Therapy

Awards/Recognition

Active Grant Awards

National Institute of Allergy and Infectious Disease (NIH) Excoffon (PI); 9/25/17-8/31/22, 1R01AI127816-01A1

 “Prevention of adenovirus pathogenesis through downregulation of the apical adenovirus receptor”; The molecular mechanism and anti-adenovirus efficacy of novel molecules that downregulate the expression of the apical adenovirus receptor and adenovirus infection will be investigated in epithelia in vitro and in the cotton rat model for adenovirus pathogenesis in vivo.

 

Department of Defense, Congressionally Directed Medical Research Programs (CDMRP) Medvedev (PI)

2016 Peer Reviewed Medical Research Program (PRMRP) Discovery Award; 5/1/17-4/30/19, PR162039, 

“Real-Time Detection of Cellular Respiratory Biomarkers of Early-Stage Infections Using Terahertz Sensing”; The identification of tissue specific respiratory bio-markers would allow real time detection of metabolic changes that occur during disease. We will study variability of respiration associated with viral infections (adenovirus) and basic metabolic changes in primary airway cells in comparison to liver cells.

Role: Co-PI

 

Is this you? Log in to update your profile.