Photo of Sandra K. Weller, Ph.D.

Sandra K. Weller, Ph.D.

Professor and Chair, Department of Molecular Biology and Biophysics
Academic Office Location:
Molecular Biology and Biophysics
UConn Health
263 Farmington Avenue
Farmington, CT 06030-3205
Phone: 860-679-2310
Fax: 860-679-1239
Email: weller@nso2.uchc.edu
Website(s): Molecular Biology & Biochemistry Graduate Program
Weller Lab Page
Education
DegreeInstitutionMajor
Ph.D.University of Wisconsin Molecular Biology
B.S.Stanford UniversityBiological Sciences

Post-Graduate Training
TrainingInstitutionSpecialty
PostdoctoralHarvard Medical School Postdoctoral Research Fellow in Microbiology and Molecular Genetics

Awards
Name of Award/HonorAwarding Organization
Board of Trustees Distinguished Professor Award University of Connecticut
Recipient of mentoring awardsRotary Club and Governor’s Partnership for Prevention
Executive Leadership in Academic Medicine Fellow 2002-2003Drexel University College of Medicine
Merit Award 1997-2007NIAID
Stuart Wilson Young Faculty Award University of Connecticut Health Center
Established Investigator Award 1988-1993 American Heart Association
Junior Faculty Research Award 1985-1988 American Cancer Society
Basil O’Connor Research Award 1985-1987 March of Dimes Foundation
Fox Award; Outstanding Undergraduate Major in Biological SciencesStanford University
Cap and Gown Award; Outstanding Junior Student in Biological SciencesStanford University
HSV-1 and -2 are large DNA virus which are responsible for oral and genital infections, sight-threatening ocular infections and brain infections which can be life threatening. Our laboratory uses genetic, biochemical, biophysical, structural and molecular approaches to elucidate mechanisms of synthesis, maturation and cleavage and packaging of viral genomes. One of our goals is to identify antiviral targets which can be exploited to develop strategies for controlling viral infections. Projects in the lab are diverse and include virus-host interactions important for the formation of replication compartments within the nucleus of infected cells; structure function analysis of two viral helicases; structure-function analysis of the zinc binding domain of the HSV-1 primase; analysis of the role of recombination in viral DNA replication and genome maturation and the analysis of the machinery involved in cleavage and packaging of viral genomes into preformed procapsids. Important recent discoveries include:

The identification and characterization of a novel viral recombinase.
The realization that host cell recombination and repair proteins are involved in HSV DNA synthesis.
The discovery that host chaperones are rearranged in infected cells into foci which act as quality control mechanisms for the production of properly folded proteins.
The finding that the initiation helicase-origin binding protein UL9 is degraded during infection in a ubiquitin mediated pathway.
The further characterization of the interdependence of the helicase and primase subunits with each other.

Accepting Lab Rotation students: Summer '14, Fall '14, Spring '15


Lab Rotation Projects

Cleavage and Packaging of Herpes Simplex Virus genomes.

Capsid assembly and genome encapsidation are critical aspects in the life cycle of any virus. Our goal is to gain a better understanding of the processes by which head to tail concatemeric DNA molecules are taken up into preassembled capsids. We have recently provided the first evidence that HSV capsids contain disulfide bonds which may be important for viral assembly and encapsidation. This rotation project will involve the introduction of mutations into the conserved cysteine residues of capsid proteins to determine whether proper disulfide bond formation is important for during infection.


The role of the cellular DNA damage response in the Herpes Simplex Virus Life Cycle.

It is becoming clear that viruses have evolved elaborate interactions with the cellular repair, recombination and checkpoint machinery in order to create an environment conducive to their own replication. The host cell’s DNA damage machinery is alert for perturbations in DNA which could lead to genetic instability. After infection, some of this machinery is inactivated by the virus in attempt to remove obstacles to productive infection; however, other components are utilized by the virus to promote viral DNA replication. In this project, aspects of this fascinating cat and mouse game will be examined.


Analysis of a viral recombinase.

UL12 and ICP8 form a two subunit viral recombinase. We have recently shown that UL12 can stimulate single strand annealing, a cellular recombination pathway. In this project, mutants in UL12 will be made to determine which residues are needed for this stimulation. UL12 also interacts with host DNA damage repair proteins and the regions of UL12 necessary for these interactions will be mapped.

Journal Articles

Books

  • Weller SK (Editor) AlphaHerpesviruses: Molecular Virology 2011 Jan;

Book Chapters

  • HSV-1 DNA Replication
    Ward, SA, Weller SK Alphaherpesviruses: Molecular Virology 2011 Jan;89-112
  • Interactions between HSV-1 and the DNA damage response
    Weitzman M, Weller SK Alphaherpesviruses: Molecular Virology 2011 Jan;257-268
  • Interaction of Marek's disease virus oncoprotein Meq with heat-shock protein 70 in lymphoid tumour cells.
    Zhao, Yuguang; Kurian, Dominic; Xu, Hongtao; Petherbridge, Lawrence; Smith, Lorraine P; Hunt, Lawrence; Nair, Venugopal The Journal of general virology 2009 Sep;90(Pt 9):2201-8
  • Herpesvirus DNA Replication
    Weller SK Viral Genome Replication 2009 Jan;
  • New HSV replication targets
    Weller SK Antiviral Therapy 2008 Jan;
  • Herpesvirus DNA replication
    Coen DM, Weller SK Eukaryotic DNA Replication and Human Disease 2006 Jan;
  • HSV-1 DNA Replication
    Weller SK Alpha Herpesviruses: Pathogenesis, Molecular Biology and Infection Control 2006 Jan;
  • Cleavage and Packaging of Herpes Simplex Virus 1 DNA
    Baines JD, Weller SK Virus packaging 2004 Jan;
  • DNA Virus replication
    Weller SK Toply and Wilson’s Microbiology and Microbial Infections:Virology Vols 1 and 2 2004 Jan;
  • Herpes simplex virus DNA replication and genome maturation
    Weller SK Implications of the DNA provirus: Howard Temin's Scientific Legacy 1995 Jan;189-213
  • Genetic Analysis of HSV Genes Required for Genome Replication
    Weller SK Herpesvirus transcription and its regulation 1990 Jan;105-135

Reviews