Marin Jukic

Marin Jukic
Karolinska Institutet | KI · Department of Physiology and Pharmacology

PhD

About

64
Publications
9,540
Reads
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658
Citations
Citations since 2017
46 Research Items
646 Citations
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2017201820192020202120222023050100150200
2017201820192020202120222023050100150200
2017201820192020202120222023050100150200
Additional affiliations
June 2011 - present
Ben-Gurion University of the Negev
Position
  • Research Assistant
Description
  • Teaching assistant for courses: Histology, Endocrinology, Cardiology, Rheumatology, and Hematology
August 2010 - October 2014
Ben-Gurion University of the Negev
Position
  • Research Assistant
Description
  • Behavioral and Pharmacology, Molecular biology, Bioinformatics

Publications

Publications (64)
Article
Aims CYP2C19 transgenic mouse expresses the human CYP2C19 gene in the liver and developing brain and it exhibits altered neurodevelopment associated with impairments in emotionality and locomotion. Since the validation of new animal models is essential for the understanding of the aetiology and pathophysiology of movement disorders, the objective w...
Article
Full-text available
Genetic factors can, to a certain extent, successfully predict the therapeutic effects, metabolism, and adverse reactions of drugs. This research field, pharmacogenomics, is well developed in oncology and is currently expanding in psychiatry. Here, we summarize the latest development in pharmacogenomic psychiatry, where results of several recent la...
Article
Full-text available
Clinical response of clozapine is closely associated with serum concentration. While tobacco smoking is the key environmental factor underlying interindividual variability in clozapine metabolism, recent genome‐wide studies suggest that CYP1A and NFIB genetic variants may also be of significant importance, but their quantitative impact is unclear....
Article
Purpose: The antidepressant vortioxetine is mainly metabolized by the polymorphic enzyme CYP2D6. The aim of this study was to investigate the absolute serum concentrations of vortioxetine and frequency of switching to an alternative antidepressant in relation to CYP2D6 genotype in a naturalistic patient population. Methods: The analyses included...
Article
Full-text available
Sertraline is a commonly used SSRI antidepressant drug, metabolised by CYP2C19 and CYP2B6, that exhibits a substantial interindividual variation in clinical response, of which only a part can be attributed to known genetic variants. In the current study we have examined the role of a newly discovered ultrarapid CYP2C:TG haplotype and CYP2B6 variant...
Article
Full-text available
The in vivo-relevant phenotype of 3D liver spheroids allows for long-term studies of, e.g., novel mechanisms of chronic drug-induced liver toxicity. Using this system, we present a novel drug-induced stress response in human and murine hepatocyte spheroids, wherein long slender filaments form after chronic treatment with four different drugs, of wh...
Article
Full-text available
The genetic background for inter‐individual variability of the polymorphic CYP2D6 enzyme activity remains incompletely understood and the role of NFIB genetic polymorphism for this variability was evaluated in this translational study. We investigated the effect of NFIB expression in vitro using 3D liver spheroids, Huh7 cells and the influence of t...
Article
The inter-individual variability in CYP2C19-mediated metabolism may affect the antidepressant treatment. The aim of this study is to evaluate differences in antidepressant efficacy and tolerability between different CYP2C19 metabolizer categories in inpatients suffering from major depressive disorder. The cohort was divided into experimental groups...
Preprint
Background: Animal models are essential for understanding etiology and pathophysiology of movement disorders. Previously, we have found that mice transgenic for the human CYP2C19 gene, expressed in the liver and developing brain, exhibit altered neurodevelopment associated with impairments of their motor function and emotionality. Objectives: To ch...
Article
Full-text available
The use of antidepressants has been steadily increasing. Even though the amount of evidence on the usefulness of personalized drug dosing in depression treatment is growing, there is still resistance and skepticism among physicians and regulators regarding the implementation of CYP450 genotyping and therapeutic drug monitoring in psychiatric clinic...
Article
Intranasal treatment with oxytocin showed beneficial effects in post-traumatic stress disorder and autism spectrum disorders; however, it was not investigated as much in depression. Keeping in mind the favorable effects of oxytocin on animal models of anxiety and depression, we postulated that synergy between prescribed first choice drugs, selectiv...
Article
Full-text available
Genetic differences in cytochrome P450 (CYP)-mediated metabolism have been known for several decades. The clinically most important polymorphic CYP enzyme is CYP2D6, which plays a key role in the metabolism of many antidepressants and antipsychotics, along with a range of non-psychiatric medications. Dose individualization based on CYP2D6 genotype...
Article
Escitalopram is one of the most commonly used antidepressant drugs but exhibits a substantial interindividual variation in clinical response. A key factor underlying response differences is the polymorphic nature of the CYP2C19 gene encoding the major enzyme responsible for escitalopram metabolism. While pre‐emptive CYP2C19 genotyping may improve e...
Article
The metabolic activity of the polymorphic CYP2D6 enzyme is dependent on the CYP2D6 genotype; however, the guidelines for translating the genotype into phenotype, which are of relevance for adequate drug dose personalization, are ambiguous. In the present study, retrospective therapeutic drug monitoring data from 4,700 CYP2D6 genotyped patients trea...
Article
Full-text available
Simultaneous quantification of multiple psychiatric drugs is important for the therapeutic drug monitoring of psychiatric patients. In addition, it would be highly advantageous if the method could be simple, straightforward, and not time-consuming. A 200 µl plasma sample was deproteinized, drugs were separated by a ZORBAX Eclipse XDB-Phenyl column...
Article
Importance Precise estimation of the drug metabolism capacity for individual patients is crucial for adequate dose personalization. Objective To quantify the difference in the antipsychotic and antidepressant exposure among patients with genetically associated CYP2C19 and CYP2D6 poor (PM), intermediate (IM), and normal (NM) metabolizers. Data Sou...
Preprint
The antidepressant vortioxetine is primarily metabolised by the polymorphic enzyme CYP2D6. The objective of this study was to investigate the effect of CYP2D6 genotype on exposure and therapeutic failure of vortioxetine. The analysis included data from CYP2D6-genotyped patients (N=458) on vortioxetine treatment from a Norwegian therapeutic drug mon...
Article
Background: Nonadherence to antipsychotics may cause relapse and hospitalizations in patients with psychotic disorders. The purpose was to quantify and compare the outpatient's nonadherence rates of atypical antipsychotics by objective detection in blood samples. Methods: Totally, 13,217 outpatients with therapeutic drug monitoring (TDM) data of...
Article
Full-text available
Early life adversities leave long-lasting structural and functional consequences on the brain, which may persist later in life. Dopamine is a neurotransmitter that is extremely important in mood and motor control. The aim of this study was to investigate the effect of maternal deprivation during the ninth postnatal day on the volume of dopaminergic...
Article
Nonadherence to oral antipsychotic drugs is a major issue in clinical psychiatry giving rise to treatment failure. Further, polypharmacy is common in the treatment of psychotic disorders due to insufficient treatment effect during monotherapy. As a potential circuit problem, we hypothesized that antipsychotic polypharmacy is associated with increas...
Article
Full-text available
In recent decades, very few new psychiatric drugs have entered the market. Thus, improvement in the use of antidepressant and antipsychotic therapy has to focus mainly on enhanced and more personalized treatment with the currently available drugs. One important aspect of such individualization is emphasizing interindividual differences in genes rel...
Article
Sertraline is an (SSRI-)antidepressant metabolized by the polymorphic CYP2C19 enzyme. The aim of this study was to investigate the impact of CYP2C19 genotype on the serum concentrations of sertraline in a large patient population. Second, the proportions of patients in the various CYP2C19 genotype-defined subgroups obtaining serum concentrations ou...
Article
BACKGROUND: The polymorphic CYP2D6 enzyme metabolises the antipsychotic drugs risperidone and aripiprazole to their active metabolites, 9OH-risperidone and dehydroaripiprazole. The aim of this study was to quantify the effect of CYP2D6 genetic variability on risperidone and aripiprazole exposure and treatment in a large patient population. METHODS...
Article
Aim: CYP2D6*9, CYP2D6*10 and CYP2D6*41 are the most frequent reduced-function CYP2D6 alleles in Caucasians. Despite lacking in vivo evidence, they are collectively classified with an enzyme activity score of 0.5. Thus, the aim of this study was to compare the functional impact of CYP2D6*9, CYP2D6*10 and CYP2D6*41 on CYP2D6 metabolism in a large pa...
Article
To determine the relationship between alterations in the activity of the enzymes participating in antioxidative defense system and neurological soft signs (NSS) in schizophrenic patients with the first episode psychosis (SFE, n = 19), patients in relapse (SR, n = 46), and healthy controls (HC, n = 20). NSS intensity and enzymatic plasma activities...
Article
The ultrarapid CYP2D6 metabolizer (UM) phenotype is caused by CYP2D6 gene duplications in some, but not all, UM individuals. CYP2D6 and the adjacent pseudogene CYP2D7 are highly homologous; however, CYP2D7 harbors a premature stop codon, which is absent in carriers of the rare CYP2D7 variant rs530303678. We addressed whether rs530303678 could gener...
Cover Page
Full-text available
This image shows a dopaminergic neuron immunostained for cytosolic tyrosine hydroxylase (red), plasma-membrane-bound dopamine transporter (green), and nuclear DAPI staining (blue). The neuron was generated from BMP5/7-treated human induced pluripotent stem cells. The BMP/SMAD pathway has a critical role in the formation of dopaminergic neurons in v...
Article
Objective: The antidepressant escitalopram is predominantly metabolized by the polymorphic CYP2C19 enzyme. The authors investigated the effect of CYP2C19 genotype on exposure and therapeutic failure of escitalopram in a large patient population. Method: A total of 4,228 escitalopram serum concentration measurements from 2,087 CYP2C19-genotyped p...
Article
Full-text available
The embryonic formation of midbrain dopaminergic (mDA) neurons in vivo provides critical guidelines for the in vitro differentiation of mDA neurons from stem cells, which are currently being developed for Parkinson’s disease cell replacement therapy. Bone morphogenetic protein (BMP)/SMAD inhibition is routinely used during early steps of stem cell...
Article
Full-text available
Hydrocephalus can occur in children alone or in combination with other neurodevelopmental disorders that are often associated with brain overgrowth. Despite the severity of these disorders, the molecular and cellular mechanisms underlying these pathologies and their comorbidity are poorly understood. Here, we studied the consequences of genetically...
Article
Molecular Psychiatry publishes work aimed at elucidating biological mechanisms underlying psychiatric disorders and their treatment
Article
The polymorphic CYP2C19 enzyme metabolizes psychoactive compounds and is expressed in the adult liver and fetal brain. Previously, we demonstrated that the absence of CYP2C19 is associated with lower levels of depressive symptoms in 1472 Swedes. Conversely, transgenic mice carrying the human CYP2C19 gene (2C19TG) have shown an anxious phenotype and...
Article
The emergence of rapid-acting antidepressants such as ketamine has motivated studies aiming to reveal the molecular mechanism of the ketamine antidepressant effect and to enable the clinical application of rapid-acting antidepressants. Here, we provide an overview of studies addressing the antidepressant effects of ketamine in depressed patients an...
Article
Preclinical Research The emergence of rapid-acting antidepressants such as ketamine has motivated studies aiming to reveal the molecular mechanism of the ketamine antidepressant effect and to enable the clinical application of rapid-acting antidepressants. Here, we provide an overview of studies addressing the antidepressant effects of ketamine in...
Article
Full-text available
Depression contributes substantially to disease burden worldwide; however despite of this, the progress in understanding its pathophysiology has been extremely slow and the discovery of new therapeutic mechanisms is at a near standstill. The molecular targets of current major classes of antidepressants were all reverse engineered from drugs previou...
Article
Full-text available
Studying the development of mesodiencephalic dopaminergic (mdDA) neurons provides an important basis for better understanding dopamine-associated brain functions and disorders and is critical for establishing cell replacement therapy for Parkinson’s disease. The transcription factors Otx2 and Lmx1b play a key role in the development of mdDA neurons...
Article
Understanding the molecular mechanisms that promote stress resilience might open up new therapeutic avenues to prevent stress-related disorders. We recently characterized a stress and glucocorticoid-regulated gene, down-regulated in renal cell carcinoma – DRR1 (Fam107A). DRR1 is expressed in the mouse brain; it is up-regulated by stress and glucoco...
Article
Full-text available
Subtle mood fluctuations are normal emotional experiences, whereas drastic mood swings can be a manifestation of bipolar disorder (BPD). Despite their importance for normal and pathological behavior, the mechanisms underlying endogenous mood instability are largely unknown. During embryogenesis, the transcription factor Otx2 orchestrates the geneti...
Patent
Full-text available
A method for evaluating the efficacy of a candidate drug for the treatment of a bipolar disorder is provided. The method includes administering the candidate drug or combination of drugs to a mouse characterized by an elevated amount of Otx2 protein in the hindbrain; and evaluating the extent, frequency and/or reversal of a mouse behaviour that is...

Questions

Questions (4)
Question
Does someone know a good ELISA kit to detect mouse BDNF protein from brain homogenate?
Question
.csv file should include information about every pixel. Namely X-coordinate, Y-coordinate, RED intensity, GREEN intensity, and BLUE intensity.
Preferably every pixel would represent a row.
The aim is to run an R or KNIME script on every pixel and than to convert it back to picture.
Question
Does anyone know a good GFP-knockin mouse (GAD67/GAD65) for detection of GABAergic interneuronal migration in embryos (e14.5 - P0)? PV neuronal sub-population is the focus, but the preference is that GFP marks all interneurons. It would be good if the strain is commercially available.
Question
Wnt, Hh, Bmp's etc. Gene-expression/ protein changes marking stages in normal colon development

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Projects

Project (1)
Project
My current project aims to reveal the role of CYP2C19 enzyme in prenatal brain development, as well as its role in adulthood in affective disorders and metabolism of psychopharmaceuticals.