SCIENTIFIC REPORT 2004 - Sylvester Comprehensive Cancer Center

V I R A L O N C O L O G Y P R O G R A M
Obuchi, M, Fernandez, M, and Barber, GN. Development
of recombinant vesicular stomatitis
viruses that exploit defects in host defense to augment
specific oncolytic activity. Journal of Virology
77:8843-56, 2003.
Ghosh, SK, Wood, C, Boise, LH, Mian, AM,
Deyev, VV, Feuer, G, Toomey, NL, Shank, NC,
Cabral, L, Barber, GN, and Harrington, WJ Jr.
Potentiation of TRAIL-induced apoptosis in primary
effusion lymphoma through
azidothymidine-mediated inhibition of NFkappa
B. Blood 101:2321-7, 2003.
Balachandran, S and Barber, GN. Defective
translational control facilitates vesicular stomatitis
virus oncolysis. Cancer Cell 5:51-65, 2003.
Poroniscu, M, Mian, A, and Barber, GN. The
oncolytic effect of recombinant vesicular stomatitis
virus is enhanced by expression of the fusion
cytosine deaminase/uracil phosphoribosyltransferease
suicide gene. Cancer Research 63:8366-76, 2003.
HIGHLIGHTS/DISCOVERIES
• Discovered that IFN-inducible protein kinase
PKR is a critical mediator of innate immunity
to a number of viruses, since mice lacking this
kinase are very susceptible to lethal infection by
several viruses at doses that are innocuous to
wild type mice.
• Discovered that VSV has potent oncolytic (antitumor)
properties. Dr. Barber’s laboratory has
shown that VSV replicates to high levels in tumorigenic,
but not normal cells, and has identified
defects in IFN signaling and translational
control in tumorigenic cells as possible reasons
for this uncontrolled replication.
• Developed recombinant VSV that expresses
other virus proteins, such as from HCV and
HPV (implicated in tumorigenesis), as possible
vaccines for these viruses.
• Constructed VSV variants expressing suicide
cassettes and immunomodulatory genes in an
effort to increase the potency and specificity of
VSV oncolysis.
PAUL E. BOEHMER, PH. D.
Associate Professor of Biochemistry and
Molecular Biology
DESCRIPTION OF RESEARCH
Researchers in Dr. Boehmer’s laboratory are
studying molecular mechanisms of replication
and recombination in herpes simplex virus
type-1 (HSV-1). HSV-1 serves as an excellent
system in which to study DNA transactions.
Hence, like eukaryotic chromosomes, the HSV-1
genome contains multiple origins of replication.
Replication of the HSV-1 genome is mediated by
the concerted action of several virus-encoded proteins
that are thought to assemble into a
multiprotein complex. Several host-encoded factors
have also been implicated in viral DNA replication.
Furthermore, replication of the HSV-1
genome is known to be closely associated with
homologous recombination, which may function
in the initiation of DNA replication and in maintaining
genome stability. Moreover, the virusencoded
enzymes also provide a system in which
to investigate the interaction of DNA replication
enzymes with DNA damage.
HSV-1 also is the prototypic herpes virus
and therefore serves as a model to understand the
mechanism of replication of this class of virus. In
this regard, HSV-1 is one of eight human herpes
viruses that are known to cause diverse diseases
ranging from cold sores and chicken pox to mononucleosis
and even cancer. The high incidence of
herpes viruses in the human population and the
increased susceptibility of immunocompromised
individuals to these viruses make them a very important
public health problem. HSV-1 in particular
is the cause of oro-labial lesions as well as
more serious encephalitis and corneal blindness.
Most recently, Dr. Boehmer’s laboratory has
proposed to examine how the virus initiates replication
at an origin, the role recombination plays
during initiation and at later times during the
replicative cycle, how leading and lagging strand
DNA synthesis are coordinated at the viral replication
fork, and finally, the mechanism whereby
UM/Sylvester Comprehensive Cancer Center Scientific Report 2004 135