Anisa Kaenjak Angeletti, PhD

Select Publications

1. Kaenjak-Angeletti, A. and J. Ross. 2005. Cap-dependent mRNA Decay Mediated by a Herpes Simplex Virus-encoded Protein. In preparation.

2. Keeling, K., J. lanier, M. Du, J. Salas-marco, L. Gao, A. Kaenjak-Angeletti, and D. M. Bedwell. 2004. Leaky Termination at a Premature Stop Codon Antigonizes Nonsense-Mediated mRNA Decay in Saccharomyces cerevisiae. RNA 10(4):691-703.

3. Bedwell, D., A. Kaenjak, D. Benos, Z. Bebock, J. Clancy, J. Hong, A. Tousson, J. Bubien, and E. Sorscher. 1997. Aminoglycoside Antibiotics Restore CFTR Function by Suppressing Genomic Premature Stop Mutations. Nature Med. 3:1280-1284.

4. Townsend, D. E., A. Kaenjak, R. K. Jayaswal, and B. J. Wilkinson. 1996. Proline Is Biosynthesized from Arginine in Staphylococcus aureus. Microbiology 142:1491-1497.

5. Stimeling, K. W., J. E. Graham, A. Kaenjak, and B. J. Wilkinson. 1994. Evidence for
Feedback (Trans) Regulation of and Two Systems for Glycine Betaine Transport by
Staphylococcus aureus. Microbiology 140:3139-3144.

6. Kaenjak, A., J. E. Graham, and B. J. Wilkinson. 1993. Choline Transport Activity in
Staphylococcus aureus Induced by Osmotic Stress and Low Phosphate Concentrations.
J. Bacteriol. 175(8):2400-2406.

Selected Abstracts:

1. A. Kaenjak-Angeletti and J. Ross. 2002. Cap-dependent mRNA Decay by Virion Host Shutoff Protein of Herpes Simplex Virus in Vivo. The Seventh Annual Meeting of the RNA Society. Madison, WI. Abstract number 325.

2. D. Bedwell, A. Kaenjak, B. Bonetti, L. Fu, and J. Moon. 1996. Modulation of Translation Termination in S. cerevisiae. Yeast Genetics and Molecular Biology Meeting. Madison, WI. Abstract number 52A.

3. D. Bedwell, A. Kaenjak, D. Benos, J.P. Clancy, Z. Bebok, J. Hong, J. Bubien, and E. Sorscher. 1996. Aminoglycosides Restore CFTR Function in the IB3-1 CF Cell Line by Suppressing Premature Stop Mutations. The Tenth Annual North American Cystic Fibrosis Conference. Orlando, FL. Abstract number 175.

4. A. Kaenjak, and D. M. Bedwell. 1996. Biochemical Characterization Reveals Molecular Defects Caused by CF-associated Mutations in the First LSGGQ Motif of Ste6p NBD1. The Tenth Annual North American Cystic Fibrosis Conference. Orlando, FL. Abstract number 145.

5. A. Kaenjak and D. M. Bedwell. 1996. Suppression of Translation Termination by Aminoglycoside Antibiotics. The Third Annual Southeastern Yeast Regional Meeting. Hattiesburg, MS.. Abstract number 16B.

6. A. Kaenjak, J. E. Graham, and B. J. Wilkinson. 1993. Choline Transport Activity in Staphylococcus aureus Induced by Osmotic Stress and Low Phosphate. Annual Meeting of the American Society for Microbiology (ASM). Atlanta, GA. Abstract number K174.

7. A. Kaenjak and B. J. Wilkinson. 1994. Survey of Osmoregulation in Coagulase-Positive and –Negative Staphylococci. Annual Meeting of the American Society for Microbiology (ASM). Las Vegas, NV. Abstract number K57.

8. A. Kaenjak and B. J. Wilkinson. 1991. Roles of Various Osmoregulating Molecules in the Staphylococcus aureus Response to Hyperosmotic Stress. Gordon Research Conference on Staphylococcal Diseases. Newport, RI.

9. A. Kaenjak and B. J. Wilkinson. 1991. Roles of Various Osmoregulating Molecules in the Staphylococcus aureus Response to Hyperosmotic Stress. Annual Meeting of the
American Society for Microbiology (ASM). Dallas, TX. Abstract number K122.

Education

Illinois State University
PhD, Biological Sciences, 1988-1993

Mahidol University, Bangkok, Thailand
MS, Microbiology, 1981-1984

Chulalongkorn University, Bangkok, Thailand
BS, Microbiology, 1977-1981

Professional Positions:

2003 - Present
Research Assistant Professor
Nebraska Center for Virology
School of Biological Sciences
University of Nebraska, Lincoln, NE

1999 - 2003
Assistant Scientist
McArdle Laboratory for Cancer Research
University of Wisconsin-Madison, Madison, WI

1998 – 1999
Research Associate
Department of Biomolecular Chemistry
University of Wisconsin-Madison, Madison, WI

1993 - 1997
Postdoctoral Fellow
Cystic Fibrosis Foundation Postdoctoral Fellowship
Department of Microbiology
University of Alabama at Birmingham, Birmingham, AL

1988 - 1993
Teaching and Research Assistant
Microbiology Group, Department of Biological Sciences
Illinois State University, Normal, IL

1986 – 1988
Instructor
Department of Microbiology, Faculty of Medicine
Srinakharinwirot University, Bangkok, Thailand

1984 -1986
Teaching and Research Assistant
Departments of Microbiology and Biotechnology, Faculty of Science
Mahidol University, Bangkok, Thailand

Professional Affiliations

Membership, American Society for Microbiology (ASM), 1989-present

Membership, American Association for Advancement of Science (AAAS), 1990-present

Research Interests

My research interest is in messenger RNA turnover in mammalian cells induced by viral infections. Stability of mRNA controls the translatability of gene products. Viruses perturb this dynamic in order to take advantage of cellular resources for the purpose of viral replication. I use the Herpes simplex virus type 1 (HSV-1) as a model for my study. Herpes simplex virus (HSV) is a member of alpha-or neuro-tropic herpesviruses, which are enveloped DNA viruses. HSV has a wide range of susceptible host cells and causes diseases in humans from oral cold sores to ocular and genital lesions, and is a major cause of neonatal infections. Approximately 60 million people in the US are chronically infected with HSV. HSV-1 also has a potential as a vector for gene therapy to neurons. HSV encodes a protein known as virion host shutoff (vhs) protein, which mediates massive destruction of both cellular and viral mRNAs in infected cells without affecting rRNA or tRNA. The biological activity of the vhs protein results in a shutoff of host cell protein synthesis. The precise mechanism by which vhs specifically targets mRNA for degradation in infected cells remains unclear. My research is aimed at understanding how the vhs protein functions and how it induces mRNA degradation specifically without affecting rRNA and tRNA.How does the vhs protein specifically target mRNA for degradation in infected cells? The cell-free assays of vhs activity fail to mimic all the in vivo properties of the vhs protein. In particular, mRNA and non-mRNA substrates are degraded to similar extents. I aim to understand the underlying mechanism controlling the target specificity of the vhs protein of HSV-1 in infected cells. I have discovered that the vhs-mediated mRNA decay activity is strictly dependent upon the 5'cap structure of mRNA targets in infected cells. It is well known that the 5'cap structure of mRNA is important in both mRNA stability and translation initiation. But surprisingly, I found that the 3' poly(A) tail of the RNA molecule is not required for vhs targeting. I also discovered that the internal ribosome entry site (IRES) located in the 5' untranslated region (UTR) of some cellular mRNAs, but not in the intercistronic region of a bicistronic mRNA, can block the vhs activity to target mRNA for degradation in infected cells. Important questions to be addressed are:

How does the vhs protein specifically target the 5'cap of mRNA for degradation? How do some IRES block vhs activity to degrade mRNA in infected cells? What is(are) RNA binding domain(s) of the vhs protein?

How do host cells contribute to the vhs function in infected cells? My observation that mRNA decay by the vhs protein is cap-dependent indicates the link between 5' terminus of mRNA and the vhs-induced mRNA decay mechanism. The 5' cap of mRNA is important in providing stability and for its ability to initiate translation. Stability of mRNA and translation initiation processes involves several cellular factors. It is my interest to investigate the host-virus interaction that favors the activity of the vhs protein in infected cells.

How do potential cis-acting element(s) of the vhs protein and trans-acting factor(s) of host cells involved in regulation of the function of the vhs protein?