University of Nebraska-Lincoln
School of Veterinary and Biomedical Sciences
139 Morrison Center
Lincoln, NE 68583-0900
Telephone: (402) 472-4154
Fax: (402) 472-3323
- Research Program
- Selected Recent Publications
- Professional Positions
- Honors, Awards, and Affiliations
- Latest News
General Areas of Research Interest:
♦ Understand how viruses re-route host signaling cascades to determine the outcomes of infection
♦ Characterize and potentially exploit mechanisms poxviruses use to inactivate host defense pathways
♦ Apply biochemistry, functional genomics, and comparative virology in an integrated approach to determine how protein phosphorylation regulates virus-host interaction
In the Wiebe Lab we are curious about numerous aspects of pathogen-host interaction, and focus on what poxviruses can teach us about this topic. Poxviruses dedicate at least a third of their large genomes to encoding proteins involved in interacting with the host, providing us with an example of how sophisticated a virus can be in altering host function. Intriguingly, poxvirus genes are often similar to some host genes, allowing the virus to mimic the cell in some ways during infection. We are fascinated with these examples of mimicry, and work to dissect whether the similar viral and host factors perform the same functions or not. In many cases, we observe that the viral factor performs slightly differently, informing us about the ways that viruses can manipulate cells to favor their own replication.
Much of our research focuses on vaccinia virus, which is a member of the poxvirus family, and is closely related to the smallpox and monkeypox viruses. Vaccinia was given as a live vaccine against smallpox during the World Health Organization’s successful campaign to eradicate smallpox 30 years ago. Our research with vaccinia has led to the discovery that during replication of the viral DNA, vaccinia must evade a cellular protein called BAF, which would otherwise bind to the viral DNA and inhibit its replication. The virus evades BAF by inactivating its DNA binding capability via phosphorylation of BAF by a viral kinase that is a mimic of cellular enzymes. These studies indicate that BAF is a novel type of host defense against viral DNA, which may in fact extend to other sources of foreign DNA, including other viruses and potentially bacteria. Furthermore, BAF is expressed in most cell types and thus is likely to be a general DNA-specific defense in a wide range of tissues.
Interestingly, we have recently found that some vaccinia proteins inhibit BAF while others may be capable of activating it in certain situations, indicating that the role of BAF during infection is more complex than we previously thought. Future research is directed toward understand how virus and host signaling pathways converge on BAF and related proteins and determine the outcome of infection.
Selected Recent Publications
University of Nebraska-Omaha, Omaha, NE
University of Nebraska Medical Center, Omaha, NE (Eppley Institute for Research in Cancer and Allied Diseases and the Dept. of Pathology & Microbiology)
2015 – present Associate Professor, University of Nebraska-Lincoln, Lincoln, NE
2009-2015 Assistant Professor, University of Nebraska-Lincoln, Lincoln, NE
2003-2009 Postdoctoral Fellow, Medical College of Wisconsin, Department of Microbiology and Molecular Genetics, Milwaukee, WI. Advisor: Paula Traktman, Ph.D.
1998-2003 Graduate Training, University of Nebraska Medical Center, Department of Cell Biology, Omaha, NE. Advisor: Angie Rizzino, Ph.D.
Honors, Awards, and Affiliations
2015-2020 R01 Award from the NIAID entitled “MECHANISM OF THE ANTIVIRAL ACTIVITY OF BAF AGAINST POXVIRUS AND HSV-1 INFECTION”
2013-2015 R56 Award from the NIAID entitled “INTRACELLULAR DEFENSES AGAINST FOREIGN DNA: INSIGHTS FROM POXVIRUS-INFECTED CELLS”
2010-2012 K22 Award from the NIAID entitled “BAF: An Intrinsic Host Defense Responsive to Foreign DNA”
2004-2006 Postdoctoral Training Grant - Great Lakes Regional Center of Excellence for Biodefense and Emerging Disease
Member of: American Association for the Advancement of Science; American Society for Virology