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DESCRIPTION OF INTERESTS
Research focus is the improvement of cancer chemotherapy by understanding the factors that contribute to interindividual variability in drug response.
Dr. Blanco‘s goal is to perform translational research using a combination of approaches based on a) the analysis of biological samples from selected
populations, and b) the use of informative laboratory models.
A project in Dr. Blanco‘s laboratory is related to the understanding of the factors that govern interindividual variability in the metabolism and
disposition of the anthracyclines doxorubicin and daunorubicin. It is possible that specific sequence variations in genes associated with the
metabolism and disposition of anthracyclines may impact the risk of cardiotoxicity in some individuals. Our efforts are focused on the discovery and
characterization of novel single-nucleotide polymorphisms in a family of genes involved in the metabolism of anthracyclines in liver, heart and
different types of tumors (e.g. breast and lung cancer). We are investigating the extent of DNA sequence variation in these selected gene candidates
among normal individuals from different ethnic groups. We will study genotype-phenotype correlations by using paired tissue-DNA-RNA samples available
from my collaborators from the Pharmacogenetics of Anticancer Agents Research group (PAAR,http://www.pharmacogenetics.org/), and from the Roswell Park Cancer Institute (RPCI, http://www.roswellpark.org/document_9.html). We will expand our studies to characterize the
functional effect of the genetic variants by using different in-vitro and in-vivo models (e.g. cultures of hepatocytes,
cardiomyocytes, transgenic mice).
Our findings are being translated into informative case-control epidemiological studies. I am a co-investigator in the project entitled "Cardiac events
among survivors of childhood and adolescent cancer - Role of gene-environment interactions" (PI: Smita Bhatia, City of Hope National Medical Center,
CA). The project is sponsored by the Childhood Cancer Survivor Study Group (The Children‘s Oncology Group http://www.childrensoncologygroup.org/), and supported by a grant from the Lance Armstrong
Foundation. We are analyzing the distribution of the candidate polymorphisms in identically treated patients who have vs. have not developed congestive
heart failure (CHF) after anthracycline treatment for childhood cancer. In the future, individualizing the dosing of anthracyclines based on genetic
characteristics might minimize the occurrence of adverse effects.
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EXPERTISE
Research focuses on the pharmacogenomics of the treatment and management of myeloid malignancies and other cancers. |
PUBLICATIONS
| Gonzalez-Covarrubias V, Zhang J, Kalabus JL, Relling MV, Blanco JG; Pharmacogenetics of Human Carbonyl Reductase 1 (CBR1) in Livers from Black and White Donors.; Drug Metab Dispos; 2008 Nov; |
| Gonzalez-Covarrubias V, Kalabus JL, Blanco JG; Inhibition of polymorphic human carbonyl reductase 1 (CBR1) by the cardioprotectant flavonoid 7-monohydroxyethyl rutoside (monoHER).; Pharm Res; 2008 Jul; 25(7); 1730-1734 |
| Blanco JG, Leisenring WM, Gonzalez-Covarrubias VM, Kawashima TI, Davies SM, Relling MV, Robison LL, Sklar CA, Stovall M, Bhatia S; Genetic polymorphisms in the carbonyl reductase 3 gene CBR3 and the NAD(P)H:quinone oxidoreductase 1 gene NQO1 in patients who developed anthracycline-related congestive heart failure after childhood cancer.; Cancer; 2008 Jun; 112(12); 2789-2795 |
| Vicente-Serrano J, Caballero ML, Rodríguez-Pérez R, Carretero P, Pérez R, Blanco JG, Juste S, Moneo I; Sensitization to serum albumins in children allergic to cow‘s milk and epithelia.; Pediatr Allergy Immunol; 2007 Sep; 18(6); 503-507 |
| Gonzalez-Covarrubias V, Ghosh D, Lakhman SS, Pendyala L, Blanco JG; A functional genetic polymorphism on human carbonyl reductase 1 (CBR1 V88I) impacts on catalytic activity and NADPH binding affinity.; Drug Metab Dispos; 2007 Jun; 35(6); 973-980 |
| Lakhman SS, Chen X, Gonzalez-Covarrubias V, Schuetz EG, Blanco JG; Functional characterization of the promoter of human carbonyl reductase 1 (CBR1). Role of XRE elements in mediating the induction of CBR1 by ligands of the aryl hydrocarbon receptor.; Mol Pharmacol; 2007 Jun; 72(3); 734-743 |
| Weiss JR, Baer MR, Ambrosone CB, Blanco JG, Hutson A, Ford LA, Moysich KB; Concordance of pharmacogenetic polymorphisms in tumor and germ line DNA in adult patients with acute myeloid leukemia.; Cancer Epidemiol Biomarkers Prev; 2007 May; 16(5); 1038-1041 |
| Covarrubias VG, Lakhman SS, Forrest A, Relling MV, Blanco JG; Higher activity of polymorphic NAD(P)H:quinone oxidoreductase in liver cytosols from blacks compared to whites; Toxicol Lett; 2006 Jul; 164(3); 249-258 |
| Choi JY, Nowell SA, Blanco JG, Ambrosone CB; The role of genetic variability in drug metabolism pathways in breast cancer prognosis.; Pharmacogenomics; 2006 Jun; 7(4); 613-624 |
| Lakhman SS, Ghosh D, Blanco JG; Functional significance of a natural allelic variant of human carbonyl reductase
3 (CBR3).; Drug Metab Dispos; 2005 Feb; 33(2); 254-257 |
| Schuetz EG, Relling MV, Kishi S, Yang W, Das S, Chen P, Cook EH, Rosner GL, Pui CH, Blanco JG, Edick MJ, Hancock ML, Winick NJ, Dervieux T, Amylon MD, Bash RO, Behm FG, Camitta BM, Raimondi SC, Goh BC, Lee SC, Wang LZ, Fan L, Guo JY, Lamba J, Lim R, Lim HL, Ong AB, Lee HS, Kuehl P, Zhang J, Lin Y, Assem M, Schuetz J, Watkins PB, Daly A, Wrighton SA, Hall SD, Maurel P, Brimer C, Yasuda K, Venkataramanan R, Strom S, Thummel K, Boguski MS; PharmGKB update: II. CYP3A5, cytochrome P450, family 3, subfamily A, polypeptide 5.; Pharmacol Rev; 2004 Jun; 56(2); 159-159 |
| Blanco JG, Edick MJ, Relling MV; Etoposide induces chimeric Mll gene fusions.; FASEB J; 2004 Jan; 18(1); 173-175 |
| Relling MV, Boyett JM, Blanco JG, Raimondi S, Behm FG, Sandlund JT, Rivera GK, Kun LE, Evans WE, Pui CH; Granulocyte colony-stimulating factor and the risk of secondary myeloid malignancy after etoposide treatment.; Blood; 2003 May; 101(10); 3862-3867 |
| Blanco JG, Edick MJ, Hancock ML, Winick NJ, Dervieux T, Amylon MD, Bash RO, Behm FG, Camitta BM, Pui CH, Raimondi SC, Relling MV; Genetic polymorphisms in CYP3A5, CYP3A4 and NQO1 in children who developed therapy-related myeloid malignancies.; Pharmacogenetics; 2002 Nov; 12(8); 605-611 |
| Dervieux T, Blanco JG, Krynetski EY, Vanin EF, Roussel MF, Relling MV; Differing contribution of thiopurine methyltransferase to mercaptopurine versus thioguanine effects in human leukemic cells.; Cancer Res; 2001 Aug; 61(15); 5810-5816 |
| Blanco JG, Dervieux T, Edick MJ, Mehta PK, Rubnitz JE, Shurtleff S, Raimondi SC, Behm FG, Pui CH, Relling MV; Molecular emergence of acute myeloid leukemia during treatment for acute lymphoblastic leukemia.; Proc Natl Acad Sci U S A; 2001 Aug; 98(18); 10338-10343 |
| Blanco JG, Gil RR, Bocco JL, Meragelman TL, Genti-Raimondi S, Flury A; Aromatase inhibition by an 11,13-dihydroderivative of a sesquiterpene lactone.; J Pharmacol Exp Ther; 2001 Jun; 297(3); 1099-1105 |
| García F, Blanco JG, Garcés M, Juste S, Fuentes M, Herrero D; Freezing protects against allergy to Anisakis simplex.; J Investig Allergol Clin Immunol; 2001 Jan; 11(1); 49-52 |
| Blanco JG, Harrison PL, Evans WE, Relling MV; Human cytochrome P450 maximal activities in pediatric versus adult liver.; Drug Metab Dispos; 2000 Apr; 28(4); 379-382 |
| García F, Blanco JG, Marcos ML, Carretero PJ, Garcés MM, Pérez R, Alonso L, Juste S; Systemic reactions to clotiazepam.; Allergy; 1997 Jul; 52(7); 784-786 |
| Blanco JG, Gil RR, Alvarez CI, Patrito LC, Genti-Raimondi S, Flury A; A novel activity for a group of sesquiterpene lactones: inhibition of aromatase.; FEBS Lett; 1997 Jun; 409(3); 396-400 |
| Alonso L, Marcos ML, Blanco JG, Navarro JA, Juste S, del Mar Garcés M, Pérez R, Carretero PJ; Anaphylaxis caused by linseed (flaxseed) intake.; J Allergy Clin Immunol; 1996 Aug; 98(2); 469-470 |
| Alonso L, Blanco JG, Pérez R, Marcos ML, Carretero PJ, Garcés MM, Juste S, Gutierrez MC; Angiolymphoid hyperplasia with eosinophilia associated with immunotherapy.; Allergy; 1996 Mar; 51(3); 199-200 |
GRANTS
April 2004 to March 2006
Use of Stored Bone Marrow Samples for Pharmacogenetic Studies of Acute Myeloid Leukemia
National Institutes of Health
Javier Blanco
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February 2004 to December 2005
Molecular basis of polymorphic human carbonyl reductases
Kapoor Foundation
Javier Blanco
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Key adverse Events after Childhood Cancer. Follow-up of the Children’s Oncology Group Cohort
Lance Armstrong Foundation
Javier Blanco
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Pharmacogentics of Human Carbonyl Reductases
National Institutes of Health
Javier Blanco
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