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Research projects and funding in progress or
completed:
Novel feedback-regulation of xenobiotic
bioactivation
NIH, R01 GM065459 (7/03 – 8/06)
MW Linder (PI); R Valdes Jr. (Co-PI).
The objective of this research is to characterize
the molecular detail of a feedback mechanism to suppress the
bioactivation of foreign compounds during periods were cellular
detoxification pathways are becoming saturated.
Low-dose chemotherapy and celecoxib
as anti-angiogenic therapy in metastatic Ewing Sarcoma: a
biological and pharmacological companion study
AEWS02P1 (5/03 – 6/05)
S. Baruchel (PI); M. Linder (Co-Investogator).
The objective of this study is to correlate
genetic deficiency in cytochrome P4502C9 with variability
in Celecoxib metabolism in children undergoing chemotherapy.
Suppression of CYP2E1 in drug-induced
liver injury
Clinical Research Career Development Award
NIH, K23 AA014235 (4/03 – 5/08)
MW Linder (PI); R. Valdes Jr. (Mentor).
The objective of this research is to determine
whether a single nucleotide polymorphism within the human
CYP2E1 gene alters the transcriptional regulation of this
enzyme in response to drug-induced liver injury.
Beta-site evaluation of Promega READITTM
System for genotype determination and development of CYP2C9
genotyping methods
Promega Corportation (1/01 to 1/02)
MW Linder (PI); R Valdes Jr. (Co-Investigator)
Genetic mechanisms of variability in
Warfarin response
University of Louisville School of Medicine
(5/00 to 5/01)
MW Linder (PI); R Valdes Jr. and JE Adams
(Co-Investigators)
Genetic mechanisms of variability in
Warfarin response
Jewish Hospital Research Foundation (4/00
to 4/02)
MW Linder (PI),; R Valdes Jr. and JE Adams
(Co-Investigators)
Genetic basis for variability in Warfarin
maintenance dose requirement.
Jewish Hospital Research Foundation of Louisville
(3/99 to 2/02). MW Linder (PI); R Valdes Jr (Co-PI).
The objective of this translational research
is to define the diagnostic significance of cytochrome P4502C9
deficiency in terms of maintenance anticoagulation therapy
using warfarin.
Genetic Susceptibility to Vinyl Chloride-Induced
Cancer
NIH, NIEHS, R01 ES08953-01 (8/97 to 7/00)
R Valdes Jr. (PI); TE Geoghegan (Co-PI); MW
Linder (Co-Invest)
The objective of this project was to evaluate
the role of CYP2E1 and its genetic variants in susceptibility
to vinyl chloride-induced angiosarcoma
Mutation activated Ras in serum of
subjects exposed to vinyl chloride
AACC, Van Slyke Research Award (6/97 to 5/98)
MW Linder (PI);, R Valdes Jr. (Project Administrator)
Genetic Biomarkers of exposure-linked
cancer risk
NIEHS, 1P20-ES-06832 (4/96 to 3/97)
R Valdes Jr. (PI); MW Linder (Co-Investigator)
The objective of this project was to evaluate
the role of CYP2E1 and GSTM1 genetic mutations in susceptibility
to vinyl chloride-induced angiosarcoma
CYP2E1: Genetic Biomarker for VC-Induced
Angiosarcoma
NIEHS, University of Louisville Center Grant
#UL-CEHS PG95-9
(4/95 to 3/96)
R. Valdes Jr (PI); MW Linder (Co-Investigator)
The objective of this study was to develop
methods for characterization of CYP2E1 polymorphisms, including
genetic mutations and aberrant expression, in relationship
to vinyl chloride induced angiosarcoma.
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