Stapleford Lab - Microbiology

Kenneth Stapleford, PhD
Assistant Professor, Department of Microbiology
Alexandria Center for Life Science – West Tower
430 East 29th Street
Office Rm. 306
New York, NY 10016
Office: (646) 501-4641
Lab: (646) 501-4648
Email: kenneth.stapleford@nyulangone.org

 

 

KEY INTERESTS:

Arbovirus, chikungunya virus, transmission, host-pathogen, RNA viruses, genome replication, innate immunity, Sindbis virus, viral evolution, adaptation, vector-pathogen, mosquito, pathogenesis, Aedes.
 

BIOGRAPHICAL DETAILS:

Graduate Education:

Ph.D. in Cellular and Molecular Biology. University of Michigan, Ann Arbor, 2009

Postdoctoral Training:

2011-2016   Institut Pasteur, Paris
2009-2011 Yale University

Academic Appointments:

2016, Assistant Professor, Microbiology

RESEARCH INTERESTS:

Arboviruses (Arthropod-Borne) encompass a long and ever expanding list of (re)emerging human pathogens (chikungunya virus, dengue virus, Zika virus) that are of increasing global frequency, distribution, and epidemic potential. The infectious lifecycles of these viruses are complex and dynamic with the need to replicate in very disparate hosts (i.e. mosquitoes and humans). To do this, these viruses are constantly and rapidly evolving and adapting to novel environments and selective pressures. This need to evolve plays essential roles in host adaptation, vector tropism, transmission, and pathogenesis; all processes in the arbovirus lifecycle that are poorly understood.

Our lab explores the replication, evolution, and adaptation of arboviruses (chikungunya virus and Sindbis virus) in vitro and in vivo during natural transmission. We are interested in understanding the molecular rules and mechanisms that govern arbovirus replication and transmission as well as identifying potential driving forces for viral evolution in vivo. We use complementary genetic, biochemical, and in vivo insect and mammalian models, as well as a novel insect-mammal-insect transmission system to study the complete arbovirus lifecycle in the lab. In addition, we combine these in vitro and in vivo approaches with deep-sequencing and bioinformatics technologies to further explore arbovirus evolution over time and space.  

With the seemingly all too frequent (re)emergence of arboviruses in the world (chikungunya virus 2013, Zika virus 2015) it is important that we begin to study the complete lifecycle of these viruses in detail in the lab before they appear in nature. In doing this we can start to identify potential avenues for the development of antiviral therapies and vaccines targeted towards these vector-borne viruses.
 

PUBLICATIONS:

Virus-derived DNA drives mosquito vector tolerance to arboviral infection.
B. Goic, K. Stapleford, L. Frangeul, H. Blanc, L. Lambrechts, M. Vignuzzi, and MC. Saleh.
Nature Communications, In press.

Low-Fidelity Polymerases of Alphaviruses Recombine at Higher Rates To Overproduce Defective Interfering Particles.
Poirier EZ, Mounce BC, Rozen-Gagnon K, Hooikaas PJ, Stapleford KA, Moratorio G, Vignuzzi M.
J Virol. 2015 Dec 16;90(5):2446-54. doi: 10.1128/JVI.02921-15.
PMID: 26676773

Whole-Genome Sequencing Analysis from the Chikungunya Virus Caribbean Outbreak Reveals Novel Evolutionary Genomic Elements.
Stapleford KA, Moratorio G, Henningsson R, Chen R, Matheus S, Enfissi A, Weissglas-Volkov D, Isakov O, Blanc H, Mounce BC, Dupont-Rouzeyrol M, Shomron N, Weaver S, Fontes M, Rousset D, Vignuzzi M.
PLoS Negl Trop Dis. 2016 Jan 25;10(1):e0004402. doi: 10.1371/journal.pntd.0004402. eCollection 2016 Jan.
PMID: 26807575

Inhibition of mTORC1 Enhances the Translation of Chikungunya Proteins via the Activation of the MnK/eIF4E Pathway.
Joubert PE, Stapleford K, Guivel-Benhassine F, Vignuzzi M, Schwartz O, Albert ML.
PLoS Pathog. 2015 Aug 28;11(8):e1005091. doi: 10.1371/journal.ppat.1005091. eCollection 2015 Aug.
PMID: 26317997

Viral Polymerase-Helicase Complexes Regulate Replication Fidelity To Overcome Intracellular Nucleotide Depletion.
Stapleford KA, Rozen-Gagnon K, Das PK, Saul S, Poirier EZ, Blanc H, Vidalain PO, Merits A, Vignuzzi M.
J Virol. 2015 Nov;89(22):11233-44. doi: 10.1128/JVI.01553-15. Epub 2015 Aug 26.
PMID: 26311883

Emergence and transmission of arbovirus evolutionary intermediates with epidemic potential.
Stapleford KA, Coffey LL, Lay S, Bordería AV, Duong V, Isakov O, Rozen-Gagnon K, Arias-Goeta C, Blanc H, Beaucourt S, Haliloğlu T, Schmitt C, Bonne I, Ben-Tal N, Shomron N, Failloux AB, Buchy P, Vignuzzi M.
Cell Host Microbe. 2014 Jun 11;15(6):706-16. doi: 10.1016/j.chom.2014.05.008.
PMID: 24922573

Alphavirus mutator variants present host-specific defects and attenuation in mammalian and insect models.
Rozen-Gagnon K, Stapleford KA, Mongelli V, Blanc H, Failloux AB, Saleh MC, Vignuzzi M.
PLoS Pathog. 2014 Jan;10(1):e1003877. doi: 10.1371/journal.ppat.1003877. Epub 2014 Jan 16.
PMID: 24453971

Hepatitis C virus NS2 coordinates virus particle assembly through physical interactions with the E1-E2 glycoprotein and NS3-NS4A enzyme complexes.
Stapleford KA, Lindenbach BD.
J Virol. 2011 Feb;85(4):1706-17. doi: 10.1128/JVI.02268-10. Epub 2010 Dec 8.
PMID: 2114792

Complementary transcriptomic, lipidomic, and targeted functional genetic analyses in cultured Drosophila cells highlight the role of glycerophospholipid metabolism in Flock House virus RNA replication.
Castorena KM, Stapleford KA, Miller DJ.
BMC Genomics. 2010 Mar 17;11:183. doi: 10.1186/1471-2164-11-183.
PMID: 20236518

Mitochondrion-enriched anionic phospholipids facilitate flock house virus RNA polymerase membrane association.
Stapleford KA, Rapaport D, Miller DJ.
J Virol. 2009 May;83(9):4498-507. doi: 10.1128/JVI.00040-09. Epub 2009 Feb 25.
PMID: 19244330

A functional heat shock protein 90 chaperone is essential for efficient flock house virus RNA polymerase synthesis in Drosophila cells.
Castorena KM, Weeks SA, Stapleford KA, Cadwallader AM, Miller DJ.
J Virol. 2007 Aug;81(16):8412-20. Epub 2007 May 23.
PMID: 17522196