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Richard Sutton, MD, PhD
Assistant
Professor Education: Research
Interests: Quinonez,
R, Sinha, I, Singh, I, & Sutton, RE. Genetic Footprinting of the
HIV Co-Receptor CCR5: Delineation of surface expression and viral entry
determinants. Virology 307:98-115 (2003). Quinonez,
R & Sutton, RE. Lentiviral vectors for gene delivery into
cells, DNA and Cell Biology 21: 937-951 (2002). Van
Maanen, M, Tidwell, J, Donehower, L, & Sutton, RE. Development of
an HIV cDNA expression vector. Molecular Therapy 8: 167-173, 2003.
Segall, H, Yoo, E, & Sutton, RE. Characterization and detection
of artificial replication-competent lentivirus of altered host range.
Molecular Therapy 8:118-29, 2003. Poluri
A, Maanen MV & Sutton RE. Genetic therapy for HIV/AIDS. Expert Opin
Biol Ther 3:951-63, 2003. Dai, C,
McAninch, RE & Sutton, RE. Identification of Synthetic Endothelial
Cell-specific Promoters by Use of a High Throughput Screen. J. Virology
78: 6209, 2004. Baliga,
C & Sutton, RE. The role of phenotyping and replication capacity
in anti-HIV therapeutics. Current Opinion in Molecular Therapeutics,
in press. Conklin,
LD, McAninch, RE, Schulz, D, Kaluza, GL, LeMaire, SA, Coselli, JS, Raizner,
AE, & Sutton, RE. HIV-Based Vectors and Angiogenesis Following Rabbit
Hindlimb Ischemia. J. Surgical Research, in press.
Department of Molecular Virology and Microbiology
Baylor College of Medicine
Contact Information:
rsutton@bcm.edu
713-798-4096
ScB., Undergraduate studies at Brown University, Providence, RI.
MD and PhD, Medical Scientist Training Program, Stanford University
School of Medicine, Palo Alto, CA.
Post-doctoral training at UCSF (Microbiology) and Stanford University
(Biochemistry).
Clinical Training:
Internal Medicine: Hospital of the University of Pennsylvania
(Philadelphia)
Infectious Diseases: University of California, San Francisco
Board-certified in internal medicine and infectious diseases
The laboratory focuses on the use of human immunodeficiency
virus type I (HIV)-based vectors for gene transfer purposes but also
to study HIV itself. It is well known that murine leukemia virus (MLV)
is unable to infect non-dividing cells whereas HIV has multiple gene
products which allow the pre-integration complex to be transported into
the nucleus, through intact nuclear pores. HIV-based vectors have thus
been used to efficiently transfer genes into resting or quiescent human
cells, including subsets of umbilical cord blood and bone marrow-derived
hematopoietic stem cells (HSC), defined by immunophenotyping. We are
interested in testing defined HSC subsets for their ability to be transduced
by these vectors and engraft into the bone marrow of the immunodeficient
NOD/SCID mouse. In addition, we should be able to introduce novel genes
into HSC to determine whether there are functional or phenotypic consequences.
Another cellular target of interest to us are endothelial cells, which
are poorly transduced by MLV-based vectors. Using self-inactivating
(SIN) HIV-based vectors, we have been able to identify novel endothelial
cell-specific promoters. In addition, we have placed therapeutic transgenes
(namely VEGF) into SIN HIV vectors for use in an animal model of peripheral
arterial ischemia.
The lab has also developed an HIV cDNA expression vector to allow functional
isolation of critical genes. As proof-of-concept, the cellular thymidine
kinase gene was easily isolated. We have constructed libraries from
several established human cell lines to perform various functional tests
in collaboration with other investigators, including the transduction
of senescent cells to select for anti-senescence genes. In addition,
we are attempting to identify factors that may be critical for HIV replication
in order to develop a mouse model for vaccine testing and pathogenesis.
It is now known that providing mouse cells with the HIV entry determinants
CD4 and CCR5 along with the transcriptional elongation factor cyclin
T1 are not enough to obtain efficient M-tropic viral replication. The
block appears to be at the level of Gag processing and virus release.
A cDNA library in HIV itself constructed from a T cell line may be the
ideal vehicle to isolate such a factor. We have now established several
genetic screens to identify genes critical for HIV replication. We are
also using these expression libraries to characterize factors important
for binding and entry of other viruses, such as rabies.
We have also focused our attention on using HIV and other retroviral
vectors to examine the fidelity of reverse transcriptase (RT), using
a single cycle replication assay. On the basis of this reversion assay,
the fidelity of HIV and oncoretroviral RTs is approximately 10-fold
higher than previously measured. We are exploiting this assay to examine
the effects of other viral gene products, mutant RTs, and known RT inhibitors
on RT error rate. We have also designed vectors to examine the relative
contributions of RNA polymerase II and RT to errors created during the
process of HIV replication.
Selected Publications:
Tamaki, S, Eckert, K, He, D, Sutton, R, Doshe, M, Jain, G,
Tushinksi, R, Reitsma, M, Harris, B, Tsukamoto, A, Gage, F, Weissman,
I, & Uchida, N. Engraftment of sorted/expanded human CNS stem
cells from fetal brain. J. Neuroscience Research 69: 976-986 (2002).
Van Maanen, M & Sutton, RE. Rodent models for HIV-1 infection and
disease. Current HIV Research 1: 121-130, 2003.
Segall, H & Sutton, RE. Detection of replication-competent recombinant
lentiviral particles. Methods Molecular Biology 229: 87-94, 2003.
Segall, H & Sutton, RE. Monocyte/macrophages and dendritic cells.
Methods Molecular Biology 229: 107-116, 2003.
Grimes RM, Lewis ST, Visnegarwala F, Goodly J, Sutton R, Rodriguez ñ
Barradas M. Use of bDNA testing in the immunologically non-responding
patient who has a low or undetectable viral load by RT-PCR testing.
HIV Clinical Trials 4: 92-98, 2003.
Van Maanen, M, Tidwell, J, Donehower, L, & Sutton, RE. Development
of an HIV cDNA expression vector. Molecular Therapy 8: 167-173, 2003.
Segall, H, Yoo, E, & Sutton, RE. Characterization and detection
of artificial replication-competent lentivirus of altered host range.
Molecular Therapy 8:118-29, 2003.
©2002,
Cell And Gene Therapy, Baylor College
of Medicine
One Baylor Plaza, N1002, Houston, TX 77030, (713)798-1246
URL: http://www.bcm.edu/genetherapy
Email:cagt@bcm.edu
(Modified:August 15, 2006- SM)
