Nina Isoherranen
· Professor and Milo Gibaldi Endowed Chair, PharmaceuticsUniversity of Washington · Pharmacology
Active 1999–2024
About
Dr. Nina Isoherranen is a Professor and Milo Gibaldi Endowed Chair in the Department of Pharmaceutics at the University of Washington School of Pharmacy. Her main research interests include the metabolism, disposition, and biological effects of Vitamin A and Retinoic acid, as well as drug disposition and drug safety during pregnancy. Her research program encompasses studies of the role of CYP26 and ALDH1A enzymes in Vitamin A homeostasis, alterations in the vitamin A metabolome in obesity and related comorbidities, and the characterization of how drug and vitamin metabolism change during pregnancy. She actively conducts research in pharmacokinetic modeling, molecular mechanisms of drug-drug interactions, and the development of physiologically based pharmacokinetic (PBPK) models to predict complex drug-drug and disease-drug interactions, as well as clearance changes in different physiological states. Dr. Isoherranen received her bachelor’s degree in chemistry and her master’s degree in Analytical Chemistry from the University of Helsinki in 1998. She earned her PhD in Pharmaceutical Sciences from the Hebrew University of Jerusalem in 2003 and completed post-doctoral training at the University of Washington. She joined the Department of Pharmaceutics as an Acting Assistant Professor in November 2004. Her expertise includes addiction medicine, drug discovery, drug metabolism, mechanisms of drug interactions, obesity and bariatric surgery, pharmacokinetics-pharmacodynamics, pregnancy and fetal pharmacology, and vitamins. She is involved in teaching courses such as PCEUT532, PCEUT506, and PCEUT502.
Research topics
- Computer Science
- Biology
- Medicine
- Biochemistry
- Endocrinology
- Genetics
- Pharmacology
- Internal medicine
- Computational biology
- Chemistry
- Biotechnology
- Urology
- Immunology
- Virology
- Microbiology
- Risk analysis (engineering)
- Ecology
- Zoology
Selected publications
Pharmaceutical Research · 2023 · 8 citations
- Pharmacology
- Chemistry
- Medicine
Gut commensals expand vitamin A metabolic capacity of the mammalian host
Cell Host & Microbe · 2022 · 63 citations
- Biology
- Microbiology
- Zoology
The FASEB Journal · 2022 · 10 citations
- Endocrinology
- Internal medicine
- Biochemistry
Regulation of the pyruvate dehydrogenase (PDH) complex by the pyruvate dehydrogenase kinase PDK4 enables the heart to respond to fluctuations in energy demands and substrate availability. Retinoic acid, the transcriptionally active form of vitamin A, is known to be involved in the regulation of cardiac function and growth during embryogenesis as well as under pathological conditions. Whether retinoic acid also maintains cardiac health under physiological conditions is unknown. However, vitamin A status and intake of its carotenoid precursor β-carotene have been linked to the prevention of heart diseases. Here, we provide in vitro and in vivo evidence that retinoic acid regulates cardiac Pdk4 expression and thus PDH activity. Furthermore, we show that mice lacking β-carotene 9',10'-oxygenase (BCO2), the only enzyme of the adult heart that cleaves β-carotene to generate retinoids (vitamin A and its derivatives), displayed cardiac retinoic acid insufficiency and impaired metabolic flexibility linked to a compromised PDK4/PDH pathway. These findings provide novel insights into the functions of retinoic acid in regulating energy metabolism in adult tissues, especially the heart.
Elsevier eBooks · 2021
- Computer Science
- Computer Science
3D cell culture models: Drug pharmacokinetics, safety assessment, and regulatory consideration
Clinical and Translational Science · 2021 · 203 citations
- Computer Science
- Computational biology
- Pharmacology
Nonclinical testing has served as a foundation for evaluating potential risks and effectiveness of investigational new drugs in humans. However, the current two-dimensional (2D) in vitro cell culture systems cannot accurately depict and simulate the rich environment and complex processes observed in vivo, whereas animal studies present significant drawbacks with inherited species-specific differences and low throughput for increased demands. To improve the nonclinical prediction of drug safety and efficacy, researchers continue to develop novel models to evaluate and promote the use of improved cell- and organ-based assays for more accurate representation of human susceptibility to drug response. Among others, the three-dimensional (3D) cell culture models present physiologically relevant cellular microenvironment and offer great promise for assessing drug disposition and pharmacokinetics (PKs) that influence drug safety and efficacy from an early stage of drug development. Currently, there are numerous different types of 3D culture systems, from simple spheroids to more complicated organoids and organs-on-chips, and from single-cell type static 3D models to cell co-culture 3D models equipped with microfluidic flow control as well as hybrid 3D systems that combine 2D culture with biomedical microelectromechanical systems. This article reviews the current application and challenges of 3D culture systems in drug PKs, safety, and efficacy assessment, and provides a focused discussion and regulatory perspectives on the liver-, intestine-, kidney-, and neuron-based 3D cellular models.
Scientific Reports · 2021 · 33 citations
- Virology
- Computational biology
- Medicine
Rapid generation of diagnostics is paramount to understand epidemiology and to control the spread of emerging infectious diseases such as COVID-19. Computational methods to predict serodiagnostic epitopes that are specific for the pathogen could help accelerate the development of new diagnostics. A systematic survey of 27 SARS-CoV-2 proteins was conducted to assess whether existing B-cell epitope prediction methods, combined with comprehensive mining of sequence databases and structural data, could predict whether a particular protein would be suitable for serodiagnosis. Nine of the predictions were validated with recombinant SARS-CoV-2 proteins in the ELISA format using plasma and sera from patients with SARS-CoV-2 infection, and a further 11 predictions were compared to the recent literature. Results appeared to be in agreement with 12 of the predictions, in disagreement with 3, while a further 5 were deemed inconclusive. We showed that two of our top five candidates, the N-terminal fragment of the nucleoprotein and the receptor-binding domain of the spike protein, have the highest sensitivity and specificity and signal-to-noise ratio for detecting COVID-19 sera/plasma by ELISA. Mixing the two antigens together for coating ELISA plates led to a sensitivity of 94% (N = 80 samples from persons with RT-PCR confirmed SARS-CoV-2 infection), and a specificity of 97.2% (N = 106 control samples).
Recent grants
Mechanisms of Regulation of Retinoic Acid Homeostasis
NIH · $2.6M · 2014–2024
Mechanisms of Regulation of Retinoic Acid Homeostasis
NIH · $400k · 2014–2022
Mechanisms of Regulation of Cannabinoid Disposition
NIH · $24.9M · 2013–2026
NIH · $1.7M · 2015
Frequent coauthors
- 37 shared
Alex Zelter
University of Washington
- 35 shared
R. Foti
Merck & Co., Inc., Rahway, NJ, USA (United States)
- 34 shared
Guo Zhong
University of Washington
- 33 shared
Leslie J. Dickmann
- 32 shared
Sara Shum
- 29 shared
Brian Buttrick
- 28 shared
Cathryn A. Hogarth
La Trobe University
- 26 shared
Philippe Diaz
University of Montana
Education
Ph.D., Pharmaceutical Sciences
Hebrew University of Jerusalem
M.S., Analytical Chemistry
University of Helsinki
B.S., Chemistry
University of Helsinki
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