TY - JOUR
T1 - Dr. Daniel Acosta and In Vitro toxicology at the U.S. Food and Drug Administration's National Center for Toxicological Research
AU - Inselman, Amy
AU - Liu, Fang
AU - Wang, Cheng
AU - Shi, Qiang
AU - Pang, Li
AU - Mattes, William
AU - White, Matthew
AU - Lyn-Cook, Beverly
AU - Rosas-Hernandez, Hector
AU - Cuevas, Elvis
AU - Lantz, Susan
AU - Imam, Syed
AU - Ali, Syed
AU - Petibone, Dayton M.
AU - Shemansky, Jennifer M.
AU - Xiong, Rui
AU - Wang, Yiying
AU - Tripathi, Priya
AU - Cao, Xuefei
AU - Heflich, Robert H.
AU - Slikker, William
N1 - Funding Information:
Human iPSC-CMs hold great potential for studying genotype-phenotype associations ( Sayed et al., 2016 ). Accordingly, a project is under development to identify and understand the molecular and genetic mechanisms underlying tyrosine kinase inhibitor (KI)-induced cardiotoxicity using 250 lines of hiPSC-CMs from the National Heart Lung Blood Institute (NHLBI) HyperGEN cohort. While the development of KIs has revolutionized cancer treatment ( Chen et al., 2008 ), a subset of patients treated with KIs develops cardiac dysfunction and heart failure. For many patients, KI-induced cardiotoxicity counters the benefits of these life-saving anti-cancer reagents. As little is known about the underlying pathophysiology and risk factors for KI-induced cardiotoxicity ( Ewer and Ewer, 2013 ), scientists from the Medical College of Wisconsin proposed to use hiPSC-CMs to identify genetic markers that contribute to the variability in the responses to KIs. The project has been recently funded by NHLBI with NCTR researchers as collaborators on the project. Phenotypic analysis, expression analysis, and functional assays will be performed to identify functional networks for KI-induced cardiotoxicity. GWAS and whole exome data will be used to determine variants associated with KI-induced cardiotoxic response. This project is in line with interests of NCTR in identifying novel biomarkers for drug-induced cardiotoxicity and applying innovative systems biology approaches to advance drug safety evaluation.
Publisher Copyright:
© 2019
PY - 2020/4
Y1 - 2020/4
N2 - For the past five years, Dr. Daniel Acosta has served as the Deputy Director of Research at the National Center for Toxicological Research (NCTR), a principle research laboratory of the U.S. Food and Drug Administration (FDA). Over his career at NCTR, Dr. Acosta has had a major impact on developing and promoting the use of in vitro assays in regulatory toxicity and product safety assessments. As Dr. Acosta nears his retirement we have dedicated this paper to his many accomplishments at the NCTR. Described within this paper are some of the in vitro studies that have been conducted under Dr. Acosta's leadership. These studies include toxicological assessments involving developmental effects, and the development and application of in vitro reproductive, heart, liver, neurological and airway cell and tissue models.
AB - For the past five years, Dr. Daniel Acosta has served as the Deputy Director of Research at the National Center for Toxicological Research (NCTR), a principle research laboratory of the U.S. Food and Drug Administration (FDA). Over his career at NCTR, Dr. Acosta has had a major impact on developing and promoting the use of in vitro assays in regulatory toxicity and product safety assessments. As Dr. Acosta nears his retirement we have dedicated this paper to his many accomplishments at the NCTR. Described within this paper are some of the in vitro studies that have been conducted under Dr. Acosta's leadership. These studies include toxicological assessments involving developmental effects, and the development and application of in vitro reproductive, heart, liver, neurological and airway cell and tissue models.
UR - http://www.scopus.com/inward/record.url?scp=85081110306&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85081110306&partnerID=8YFLogxK
U2 - 10.1016/j.tiv.2019.03.003
DO - 10.1016/j.tiv.2019.03.003
M3 - Review article
C2 - 31628011
AN - SCOPUS:85081110306
SN - 0887-2333
VL - 64
JO - Toxicology in Vitro
JF - Toxicology in Vitro
M1 - 104471
ER -