Dr. Laura Newcomb
Office: BI 310
Lab: BI 308
Phone: 909 537 5542
Ph.D., Biomolecular Chemistry, University of Wisconsin - Madison
NIH Postdoctoral Fellow, Institute for Cellular and Molecular Biology, University of Texas at Austin
BIOL 400 - Molecular Biology
BIOL 502 - Genetic Engineering
BIOL 572 - Virology
BIOL 592 - Recombinant DNA Techniques
BIOL 600 - Advanced Topics in Molecular Biology - RNA Biology
BIOL 677 - Advanced Topics in Immunology - Viral Immunology
Viruses are unique in that they are genetic entities which cannot reproduce on their own. In order to reproduce, a virus must infect a host cell and take control of that host cell for its own objectives; mainly to churn out new viral particles. For that reason, there is debate on whether or not viruses can be classified as "living." However, there is no debate that some viruses cause both health and economic hardships for human populations. On a brighter side, since viruses utilize cellular machinery to replicate, they have long been used as tools for elucidating cellular mechanisms. One example is the famous "Hershey-Chase" experiment carried out in 1952, where a bacteriophage (virus which infects bacteria) was used to demonstrate that DNA contains genetic information. In addition, today viruses are being studied for their usefulness as delivery vectors for gene therapy and as novel treatments targeting cancers (oncolytic viruses).
Research in my laboratory aims to understand how influenza virus hijacks our cellular machinery in order to reproduce. Seasonal influenza virus accounts for over 36,000 deaths each year in the United States alone. More worrisome however are the periodic pandemics caused by emerging influenza A subtypes. Influenza pandemics have occurred at three times in the past century (1918, 1957 and 1968) and once in the current century (2009). The most notorious being the pandemic of 1918 which is thought to have killed more people than WWI. Fortunately, the 2009 novel H1N1 influenza virus proved not as pathogenic as initially thought, resulting in fewer deaths than predicated. However, the high transmissibility saw the novel H1N1 readily sweep the globe and resulted in a high global economic burden. Recent findings that the highly pathogenic H5N1 avian influenza is able to evolve increased human transmissibility in the ferret model, has again emphasized the real possibility that a mutation or recombination event will result in the emergence of a highly pathogenic easily transmissible influenza strain that will cause a severe and deadly pandemic. As exemplified by the slow response to the spread of the 2009 novel H1N1 influenza, our lack of preparation for a possible deadly influenza outbreak makes it painfully evident that more knowledge of the basic molecular activities required for influenza replication is needed so that a universal vaccine and/or effective antiviral treatment can be discovered. Experiments performed in my laboratory utilize non-virulent lab strains of influenza A virus to address fundamental mechanisms of influenza viral replication with the overall goal to contribute to development of novel antiviral therapies.
One area of research focuses on the influenza Nucleoprotein (NP) which has greater than 90% protein sequence homology among influenza A isolates and as such may be a good target for novel antiviral therapies effective against multiple influenza A subtypes. NP plays an essential role in regulating influenza viral RNA replication and directly interacts with both viral and host factors during the influenza lifecycle. Our lab is interested in defining essential NP interactions. We are investigating the role of NP interaction with the influenza viral RNA dependent RNA polymerase, which in vitro data suggests regulates the switch from viral RNA transcription to viral RNA replication. We are also investigating the role of the N-terminus of NP, proposed to interact with the host RNA helicase UAP56. If these interactions prove essential for successful viral replication in the host cell, defining these molecular contacts may lay foundation for development of antiviral therapies which disrupt these interactions.
A second area of research aims to identify host mRNA nuclear export pathway(s) hijacked by influenza mRNAs during viral infection. Influenza transcribes its messenger RNA in the nucleus and requires the splicing of two transcripts and the nuclear export of three distinct classes of viral mRNA; spliced, intron-containing, and intron-less. At present little research is published regarding the cellular export pathway(s) utilized by influenza viral mRNAs, and the current publications report some conflicting data. Our research indicates that some influenza mRNAs utilize an as yet uncharacterized host mRNA nuclear export pathways. This area of research may lead to the discovery of atypical host mRNA nuclear export pathways and may reveal novel targets to facilitate development of innovative antiviral therapies.
Research in the Newcomb Lab is supported by the following:
- National Institutes of Health Award Number SC3GM099559 from the National Institute of General Medical Sciences, entitled "Influenza nucleoprotein interactions and viral RNA synthesis". End date 11/30/15.
- National Institutes of Health Award Number K22AI074662 from the National Institutes of Allergy and Infectious Diseases, entitled "Influenza Viral RNA Synthesis and Processing". End date 02/28/11.
- CSU Program for Education and Research in Biotechnology (CSUPERB), Research Development Grant, entitled "Clarify the role of host nuclear export factors in influenza mRNA nuclear export". End date 11/30/12.
Larsen S(G), Bui S(G), Perez V(UG), Mohammad A(UG), Medina-Ramirez H(UG) and Newcomb LL. Influenza polymerase encoding mRNAs utilize atypical mRNA nuclear export. Virol J. 2014. 11:154. PMID: 25168591
Sanchez A(G), Guerrero-Juarez CF(UG), Ramirez J(UG), Newcomb LL. Nuclear localized Influenza nucleoprotein N-terminal deletion mutant is deficient in functional vRNP formation. Virol J. 2014. 11:155. PMID: 25174360
Davis AM(G), Chabolla BJ(UG), Newcomb LL. Emerging antiviral resistant strains of Influenza A and the potential therapeutic targets within the viral ribonucleoprotein (vRNP) complex. Virol J. 2014. 11:167. PMID: 25228366
Newcomb L.L., Kuo R.L., Ye Q., Jiang Y., Tao Y.J., Krug R.M. Interaction of the influenza a virus nucleocapsid protein with the viral RNA polymerase potentiates unprimed viral RNA replication. J Virol. 2009 83(1):29-36. PMID: 18945782
Laabs, T. L., Markwardt D. D., Slattery M.G., Newcomb, L.L, Stillman D.J., and Heideman W. ACE2 is required for daughter cell-specific G1 delay in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 2003. 100(18): p. 10275-80. PMID: 12937340
Newcomb L.L., Diderich J.A., Slattery M.G., and Heideman W. Glucose regulation of Saccharomyces cerevisiae cell cycle genes. Eukaryot Cell. 2003. 2(1): p. 143-9. PMID: 12582131
Newcomb L.L., Hall D.D., and Heideman W. AZF1 is a glucose-dependent positive regulator of CLN3 transcription in Saccharomyces cerevisiae. Mol Cell Biol. 2002. 22(5): p. 1607-14. PMID: 11839825
Wu M., Newcomb L., and Heideman W. Regulation of gene expression by glucose in Saccharomyces cerevisiae: a role for ADA2 and ADA3/NGG1. J Bacteriol. 1999. 181(16): p. 4755-60. PMID: 10438741