Gary R. Whittaker - Cornell Veterinary Medicine

Dr. Whittaker is an Associate Professor in the Department of Microbiology and Immunology and has been associated with the department since 1996. He received a bachelor's degree in Biochemistry, and his Ph.D. in Microbiology from Leeds University U.K - studying the molecular biology and biochemistry of equine herpesvirus. He obtained postdoctoral training at Yale University in the laboratory of Dr. Ari Helenius, studying the cell biology of influenza virus replication. Dr Whittaker's laboratory is focused on the entry of influenza viruses, rhaboviurses and coronaviruses into host cells and is funded by research grants from the National Institutes of Health.

Research Interests | Graduate Fields | Lab Members | Related Links | Selected References

Current research interests of the Whittaker lab focus on how enveloped viruses enter host cells. The laboratory focuses on three principal viral systems; 1) influenza virus - including avian and equine influenza, 2) coronaviruses - including avian infectious bronchitis virus, feline infectious peritonitis virus (FIPV) and the SARS-coronavirus, and 3) Rhabdoviruses - vesicular stomatitis virus (VSV) and viral hemorrhagic septicemia virus (VHSV). All of these viruses enter cells following receptor binding and fusion of the virus envelope with the cell membrane. The focus of the laboratory is on how receptor utilization interfaces with the route of endocytosis, the proteolytic priming of the envelope protein and the pH-dependent activation of membrane fusion. We utilize a variety of techniques, encompassing molecular and cell biology and biochemistry, as well as structural studies of the viral fusion proteins.

	Entry of influenza viruses. We are studying the entry mechanism of influenza virus into its host in order to gain information on the pathogenic properties of the virus. Specifically, we are studying the route of endocytosis and the cell signaling pathways activated during virus entry, with the goal of identifying novel antiviral targets, and deciphering any possible co-receptor usage by the virus. From a structural point of view we are interested in the changes that occur in the viral hemagglutinin (HA) molecule that might account for different pathogenic properties as viruses emerge into new species (e.g avian-equine or avian human) and well as how the virus adapts to its new host.
	Entry of coronaviruses. We have recently developed the avian virus infectious bronchitis virus (IBV) as a system to study coronavirus entry. We have developed fluorescence dequenching assays of viral fusion to show the role of low pH for entry of IBV, and are applying these techniques to other members of the Coronaviridae. With IBV as a model, we are exploring the process of fusion activation of the SARS-coronavirus, as well as feline infectious peritonitis virus (FIPV), in order to gain molecular insight into the pathogenesis of these deadly viruses.
	Entry of rhabdoviruses. Using the information provided by the recent crystal structure of the vesicular stomatitis virus fusion (G) protein, we are carrying out a mutagenesis study to determine the critical amino acids within the fusion domain of VSV G, as well as the related fish rhabdovirus, viral hemorrhagic septicemia virus (VHSV).

Dr. Whittaker is a member of the following Graduate Fields:

Damon Ferguson, Technician (ad79@cornell.edu)
Sandrine Belouzard, Postdoctoral Associate (sb398@cornell.edu)
Michele Bialecki, Graduate Student (mab269@cornell.edu)
Xiangjie Sun, Graduate Student (xs27@cornell.edu)
Ikenna Madu, Graduate Student (im66@cornell.edu)
Lisa McElroy, DVM/PhD Student (ljm35@cornell.edu)
Andrew Regan, Graduate Student (adr32@cornell.edu)
Shoshannah Roth, Graduate Students (slr29@cornell.edu)
Rabia Aslam, Undergraduate Student (ra249@cornell.edu)
Renata Shraybman, Undergraduate Student (rs357@cornell.edu)

Selected References

Sieczkarski, S.B. and Whittaker, G.R. (2002). Dissecting virus entry via endocytosis. J. Gen Virol. 83: 1535-1545. http://www.sgm.ac.uk/JGVDirect/18346/18346ft.htm

Sieczkarski, S.B. and Whittaker, G.R. (2002). Influenza virus can infect cells in the absence of clathrin-mediated endocytosis J Virol. 76: 10455-10464.

Sun, X. and Whittaker, G.R. (2003). Role for influenza virus envelope cholesterol in virus entry and infection. J. Virol. 77: 12543-12551.

Khor, R., McElroy, L.J.. and Whittaker, G.R. (2003). The ubiquitin-vacuolar protein sorting pathway is selectively required during entry of influenza virus into host cells. Traffic 4: 857-868.

Chu VC, Whittaker GR. (2004) Influenza virus entry and infection require host cell N-linked glycoprotein. Proc Natl Acad Sci U S A. 101:18153-18158.

Chu VC, McElroy LJ, Chu V, Bauman BE, Whittaker GR. (2006) The avian coronavirus infectious bronchitis virus undergoes direct low-pH-dependent fusion activation during entry into host cells. J Virol. 80:3180-3188.