Genomes and Genes
TRAINING GRANT IN CLINICAL PHARMACOLOGY
Principal Investigator: R Weinshilboum
Affiliation: Mayo Clinic
Abstract: This proposal is a request for continued funding of the NIH-sponsored Clinical Pharmacology Fellowship Training Program at the Mayo Medical School-Mayo Clinic. Clinical Pharmacology is the study of the interaction between therapeutic agents and humans. However, in the context of the ongoing "Genomics Proteomics Revolution" in biomedical science, Clinical Pharmacology represents an important interface between basic molecular genetic, Genomic and proteomic science and rational therapeutics. Bridge disciplines such as Clinical Pharmacology are uniquely poised to take advantage of the revolution in biomedicine to apply this new scientific information at the translational interface in order to provide an understanding of the molecular basis for human response to drug therapy. However, the ability to take advantage of this unique opportunity will require the training of a new generation of Clinical Pharmacologists who are thoroughly grounded in basic molecular science and who are able to apply that science to study the interaction between patients and drugs. At this point in the Genomics-Proteomics Revolution, large comprehensive, integrated academic medical centers like the Mayo Clinic represent ideal locations for the training of this new generation of Clinical Pharmacologists. Mayo is positioned to accept this challenge because its basic science and clinical research programs are highly integrated, because it has a long history of contribution to the discipline of Clinical Pharmacology and because the Mayo Clinical Pharmacology Training Program has already had a decade of experience in successfully recruiting and training academic physicians who wish to apply biological science to Clinical Pharmacology. Fellowship Training that will emphasize a strong laboratory-based scientific experience, exposure to clinical science and highly structured and accountable mentorship is at the heart of the Mayo Clinical Pharmacology Fellowship Training Program described in this proposal.
Funding Period: 1998-07-01 - 2008-06-30
more information: NIH RePORT
- CHK1 and WEE1 inhibition combine synergistically to enhance therapeutic efficacy in acute myeloid leukemia ex vivoLeena Chaudhuri
Haematologica 99:688-96. 2014..These results indicate that combined cell cycle checkpoint interference with MK1775/MK8776 warrants further investigation as a potential treatment for acute myeloid leukemia. ..
- Oncolytic vesicular stomatitis virus and bortezomib are antagonistic against myeloma cells in vitro but have additive anti-myeloma activity in vivoDanielle N Yarde
Department of Molecular Medicine, Mayo Clinic, Rochester, MN, USA
Exp Hematol 41:1038-49. 2013....
- Alternative to ganglionic blockade with anticholinergic and alpha-2 receptor agentsBrad W Wilkins
Dept of Anesthesiology, Mayo Clinic, Rochester, MN 55905, USA
Clin Auton Res 17:77-84. 2007..05). Heart rate only decreased 1 +/- 2 bpm during GLY: -DEX: and 1 +/- 1 bpm with TMP. Taken together, our results suggest that GLY: -DEX: is a reasonable alternative to TMP for baroreflex inhibition...
- Population pharmacokinetic model for cancer chemoprevention with sulindac in healthy subjectsAlexander K Berg
Mayo Clinic, Rochester, MN 55905, USA
J Clin Pharmacol 53:403-12. 2013....
- Supplementation of nitric oxide attenuates AβPP and BACE1 protein in cerebral microcirculation of eNOS-deficient miceSusan A Austin
Department of Anesthesiology and Molecular Pharmacology, Mayo Clinic, Rochester, MN 55905, USA
J Alzheimers Dis 33:29-33. 2013..Our findings support the concept that preservation of NO/cGMP signaling is an important modulator of expression and processing of AβPP...
- The function of vascular smooth muscle phosphodiesterase III is preserved in healthy human agingRachel L Elvebak
Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota, USA
Clin Transl Sci 3:239-42. 2010..SNP responses were also similar. This study suggests that the vasodilator pathway associated with PDE III function, the bioavailability of cAMP, and the interaction with cGMP may be preserved in healthy aging...
- Simultaneous phenotyping and quantification of α-1-antitrypsin by liquid chromatography-tandem mass spectrometryYuhong Chen
Division of Clinical Pharmacology, Department of Molecular and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA
Clin Chem 57:1161-8. 2011....
- Endothelial nitric oxide modulates expression and processing of amyloid precursor proteinSusan A Austin
Departments of Anesthesiology and Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, Minn, 55905, USA
Circ Res 107:1498-502. 2010..The link between these risk factors and AD has yet to be identified; however, a common feature is endothelial dysfunction, specifically, decreased bioavailability of nitric oxide (NO)...
- CD38 expression, function, and gene resequencing in a human lymphoblastoid cell line-based model systemWilliam R Hartman
Division of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA
Leuk Lymphoma 51:1315-25. 2010..We also determined that variation in CD38 expression in these cell lines was associated with variation in antineoplastic drug sensitivity. These results represent a step toward understanding mechanisms involved in CD38 expression...
- Serum osteocalcin is associated with measures of insulin resistance, adipokine levels, and the presence of metabolic syndromeUmer Saleem
Division of Cardiovascular Diseases, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
Arterioscler Thromb Vasc Biol 30:1474-8. 2010..We investigated whether serum osteocalcin was associated with measures of insulin resistance, circulating adipokine levels, and the presence of metabolic syndrome (MetSyn)...
- Sarcolemmal ATP-sensitive K(+) channels control energy expenditure determining body weightAlexey E Alekseev
Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA
Cell Metab 11:58-69. 2010....
- Aging is associated with reduced prostacyclin-mediated dilation in the human forearmWayne T Nicholson
Department of Anesthesiology, College of Medicine, Mayo Clinic, Rochester, MN 55905, USA
Hypertension 53:973-8. 2009..Our data suggest that the reduced dilator effects of PGI(2) in older individuals are attributable to a reduction in the contribution of endothelial-derived NO versus alterations in the direct effects of PGI(2) on vascular smooth muscle...
- K(ATP) channel pharmacogenomics: from bench to bedsideS Sattiraju
Marriott Heart Disease Research Program, Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA
Clin Pharmacol Ther 83:354-7. 2008..There is an increased recognition that genetic variability of the K(ATP) channel impacts therapeutic decision-making in human disease...
- Autonomic cardiovascular control during a novel pharmacologic alternative to ganglionic blockadeB W Wilkins
Department of Anesthesiology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
Clin Pharmacol Ther 83:692-701. 2008..05) and baroreflex changes in MSNA (P<0.01). We conclude that the GLY-DEX alternative drug strategy can be used as a reasonable alternative to pharmacologic ganglionic blockade to examine autonomic cardiovascular control...
- Identification of HLA-DRB1-bound self-peptides following measles virus infectionInna G Ovsyannikova
Mayo Vaccine Research Group, 611C Guggenheim Building, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA
J Immunol Methods 297:153-67. 2005..This provides further knowledge of the changes in peptide expression after viral infection and provides a powerful tool for identifying HLA-presented host and viral epitopes in the context of class II HLA molecules...
- Identification of Th0 cells responding to measles virusRawleigh C Howe
Mayo Vaccine Research Group, Mayo Clinic and Foundation, Rochester, MN 55905, USA
Hum Immunol 66:104-15. 2005....