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Alan Davis, PhD
Education: Selected
Publications: Claudio
P.P., Fratta L., Farina F., Howard C.M., Stassi G., Numata S., Pacilio
C., Davis A., Lavitrano M., Volpe M., Wilson J.M., Rimarco B., Giordano
A., and Condorelli G. Adenoviral RB2/p130 gene transfer inhibits smooth
muscle cell proliferation and prevents restenosis after angioplasty.
Circ. Res. 85: 1032-1039 (1999).
Department of Pediatrics,
Section of Hematology-Oncology,
Baylor College of Medicine
Contact Information:
ardavis@bcm.edu
713-798-1237
BA,
University of California, Los Angeles
PhD, University of California, Los Angeles
Research Interests:
My Research Interests are in gene targeting/integration using
DNA viruses vectors, particularly adenovirus and adeno-associated
virus. The use of adenovirus would be for oncology while adeno-associated
virus, for cardiovascular disease.
1. Use of adenoviruses in gene targeting in cancer A number of
clinical studies are ongoing at our institute and others where
adenovirus is used as a vector for delivery of suicide genes such as
herpes virus thymidine kinase. In the clinical studies at our institution
an adenovirus containing the herpes simplex thymidine kinase placed
in the El region, with concomitant deletion in this region is being
used in phase I/II studies in mesothelloma and glioma. This vector is
used in combinationwith ganciclovir treatment. One problem with this approach
is that extremely large doses of vector are required since these
vectors cannot replicate. An alternative approach is to use replicating
vectors that can spread through the tumor. However, insurmountable
toxicity problems may be encountered in this approach since there
is no targeting of the vector. One way to overcome this problem
is to replace the El promoter with promoters which are highly active
in the tumor tissue that is being targeted. In this way the vector
can only replicate in the targeted tissue. The suicide gene can be
placed in another region. This approach has been recently suggested for
prostate cancer using the prostate-specific antigen promoter. In this
approach it will be important to search for promoters that are active
in the tumor tissue. Although certain promoters active in many tumors
(e.g CEA) may be evaluated, active tumorspecific promoters may be uncovered
through the hybridization of tumor-specific cDNA to microarrays.
In this way mRNAs that are highly and preferentially expressed
in the tumor tissue can be uncovered. Finally, if tumor-specific
antigens are present their cDNA(s) may be cloned by traditional
methods. These genes can be mapped and their upstream regions (promoters)
characterized and utilized. Other approaches would use adenovirus
vectors, particularly EI/E4 deletions that express cytokines know
to kill tumor cells. One of these is beta interferon. Systemic
administration of this cytokine is limited because of toxicity.
However, local delivery through the use of an EVE4 deleted adenovirus
vector with a tissue specific promoter would allow tumor killing.
2. Use of adeno-associated virus (AAV) vectors in treatment of cardiovascular
disease AAV is an integrating vector with increasing potential
In gene therapy. Infection by AAV is usually dependent on co-infection
with adenovirus. Recently, our group and others have uncovered
certain tissues that can be infected by recombinant AAV alone.
One of those is muscle. We have also shown, using AAVlacZ, that
cardiac muscle can be infected by recombiant AAV and that transgene
expression is long term and induces little immune response. Therefore
the use of this vector presents an opportunity for treatment of
cardiovascular disease. One of these is hypertrophic cardiomyopathy.
AAV vectors could be designed to transduce cardiac muscle with
troponin T and troponin I that have been shown to be mutated in
hypertrophic cardiomyopathy.
Davis, A. R. and Nayak, D.P. (1977). Expression of endogenous
retroviral genes in leukemic guinea pig cells. J . Virol. 23,
263-271.
Davis, A. R.and Nayak., D.P. (1979). Sequence relationships among influenza
defective interfering viral RNA. Proc. Natl. Acad. Sci. USA 76, 3092-3096.
Davis, A. R., Hiti, A.L., and Nayak, D.P. (1980). Influenza defective
interfering viral RNA is formed by internal deletion of genomic RNA.
Proc. Natl. Acad. Sci. USA 77, 215-219.
Davis, A. R., Nayak, D.P., Ueda, M., Hiti, A.L., Dowbenko, and Kleid,
D.G. (1981). Expression of antigenic determinants of the hemagglutinin
gene of a human influenza virus in Escherichia coli. Proc. Natl.
Acad. Sci. USA 78, 5376-5380.
Nayak, D. P., Sivasubramanian, N., Davis, A.R., Cortini, R., and Sung,
J. (1982). Complete sequence analyses show that two defective
interfering influenza viral RNAs contain a single internal deletion
of a polymerase gene. Proc. Natl. Acad. Sci. USA 79, 2216-2220.
Roth, M. G., Compans, R.W., Giusti, L., Davis, A.R., Nayak, D.P., Gething, M.J.,
and Sambrook, J. (1983). Influenza virus hemagglutinin expression is polarized
in cells infected with a recombinant SV40 virus carrying a cloned
hemagglutinin DNA. Cell 33, 435-443.
Davis, A. R., Bos, T.B., and Nayak, D.P. (1983). Active influenza virus
neuraminidase is expressed in monkey cells from cloned cDNA using simian
virus 40 vectors. Proc. Natl. Acad. Sci. USA 80, 3976-3980.
Davis, A. R., Kostek, B., Mason, B.B., Hsiao, C.L., Morin, J., Dheer,
S.K., and Hung, P.P. (1985). Expression of hepatitis-B surface antigen
with a recombinant adenovirus. Proc. Natl. Acad. Sci. USA 82, 7560-7564.
Lubeck, M. D., Davis, A.R., Morin, J.E., Molnar-Kimber, K., Chengalvala, M.,
Natuk, R., Mason, B.B., Mizutani, S., Hung, P.P., and Purcell, R. H. (1989).
Immunogenicity and efficacy testing in chimpanzees of an oral hepatitis
B vaccine based upon live recombinant adenovirus. Proc. Natl. Acad.
Sci. USA 86, 6763-6767.
Natuk, R. J., Chanda, P.K., Lubeck, M.D., Davis, A.R., Wilhelm, J.,
Hjorth, R., Wade, M.S., Bhat, B.M., Mizutani,S., Lee, S., Eichberg,
J.W., Gallo, R. C., Robert-Guroff, M., and Hung, P.P. (1992).
Adenovirus-human immunodeficiency virus (HIV) envelope recombinant
vaccines elicit high-titered HIV-neutralizing antibodies in the
dog model. Proc. Natl. Acad. Sci. USA 89, 7777-7781.
Mauro, L. J., Olmsted, E.A., Skrobacz, B.M., Mourey, R.J., Davis, A.R.,
and Dixon, J.E. (1994). Identification of a hormonally-regulated protein
tyrosine phosphatase associated with bone and testicular differentiation.
J. Biol. Chem. 269, 30659-30667.
Mauro, L. J., Olmsted, E.A., Davis, A.R., and Dixon, J.E. (1996).
Parathyroid hormone regulates the expression of the receptor protein tyrosine
phosphatase, OST-PTP, in rat osteoblast-like cells. Endrocrinology
137, 925-933.
Eck, S. L., Alavi, A., Davis, A.R., Hackney, D., Judy, K., Mollman,
J., Phillips, P.C., Wheeldon, E., and Wilson, J.M. (1996). Treatment
of advanced CNS malignancies with the recombinant adenovirus H5.010RSVTK:
A Phase I Trial. Human Gene Therapy 7, 1465-1482.
Treat, J., Kaiser, L.R., Litzky, L., Davis, A.R.,Wilson, J.M., and Albelda,
S.M. (1996). Treatment of advanced mesothilioma with the recombinant
adenovirus H5.010RSVTK: A Phase I Trial (BB-IND 6274). Human Gene
Therapy 7, 2047-2057.
Davis, A.R. and Wilson, J.M. (1996). Adenovirus Vectors. In Current
Protocols in Human Genetics, N. C. Dracopoli, Haines, J.L., Korf, B.R.,
Muir, D.T., Morton, C.C., Seidman, C.E., Seidman, J.G., and Smith, D.R.,
ed. (New York: John Wiley and Sons), pp. 12.4-12.4-16.
Lubeck, M. D., Natuk, R.N., Myagkikh, M., Kalyan, N., Aldrich, K.,
Sinangil, F., Alipanah, S., Murthy, S.C.S., Chanda, P., Nigada, S., arkham,
P.D., Zolla-Pazner, S., Steimer, K., Wade, M., Reitz, M.S., rthur,
L.O., Davis, A.R., Hung, P., Gallo, R.C., Eichberg, J., and (1997).
Long-term protection of chimpanzees against high-dose HIV-1 challenge
induced by immunization. Nature Medicine 3, 651-658.
Parry, S. H., Weitzman, M.D., Davis, A.R., Federoff, H., and Strauss,
J.F. (1998). Transduction of human trophoblastic cells by replication-deficient recombinant
viral vectors: promoting cellular differentiation affects virus
entry. Am. J. Pathol. 152, 1521-1529.
Davis, A.R. and Baker., C. (1998). Production of clinical lots of gene
therapy vectors using good manufacturing practices: experience in a
univerisity setting. In Clinical Trials of Genetic Therapy with Antisense
RNA and DNA Vectors, E. Wickstrom, ed. (New York: Marcel Dekker), pp. 101-111.
Davis, A. R., Meyers, K., and Wilson, J.M. (1998). High throughput method for
creating and screening recombinant adenovirus . Gene Therapy 5, 1148-1152.
Qin, X.-C., Tao, N., Dergay, A., Moy, P., Fawell, S., Davis, A., Wilson,
J.M., and Barsoum, J. (1998). Interferon-beta gene therapy inhibits
tumor formation and causes regression of established tumors in
immune-deficient mice. Proc. Natl. Acad. Sci. U.S.A. 95, 14411-14416.
Oka, K., Davis, A.R., and Chan, L. Recent advances in liver-directed
gene therapy: Implications for the treatment of dyslipidemia. Curr.
Opin. Lipidol. 11: 179-186 (2000)
Olmsted, E.A., Blum, J.S., Rill, D., Yotdna, P., Gugula, Z., Lindsey,
R.W., and Davis, A.R. Adenovirus-mediated BMP2 expression in human bone
marrow stromal cells. J. Cell. Biochem. 82:11-2 (2001)
Yotnda, P., Onishi, H., Heslop, H.E., Shayakhmetov, D.M., Lieber, A.,
Brenner, M.K., and Davis, A.R. Highly efficient transduction of primitive
hematopoietic stem cells by modified adenovirus. Gene Therapy 8:930-937
(2001).
Olmsted-Davis E.A., Gugala Z., Gannon F.H., Yotnda P., McAlhany R.E.,
Lindsey R.W., and Davis A.R. Use of Chimeric Adenovirus Vector Enhances
BMP2 Production and Bone Formation. Human Gene Therapy (In press).
Maria Rosa Maduro, Elizabeth Davis, Alan Davis, Dolores J. Lamb (2002)
Osteotesticular Protein Tyrosine Phosphatase (OST-PTP) Expression in
Testis. J Urol 167(5):2282-2283.
Zbigniew Gugala, Elizabeth A. Olmsted-Davis, Francis H. Gannon, Ronald
W. Lindsey, Alan R. Davis (2002) Osteoinduction by Ex Vivo Adenovirus-Mediated
BMP2 Delivery Is Independent of Cell Type (Submitted: Bone).
©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)
