Jeanette N Mcclintick

Jeanette N Mcclintick
Indiana University-Purdue University Indianapolis | IUPUI · Department of Biochemistry and Molecular Biology

Ph.D. Medical Genetics; MS Computer Science

About

120
Publications
16,746
Reads
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5,971
Citations
Citations since 2017
27 Research Items
2635 Citations
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20172018201920202021202220230100200300400500
20172018201920202021202220230100200300400500
Additional affiliations
April 2006 - present
Indiana University-Purdue University Indianapolis
Position
  • Research Assistant
Description
  • Research - genetics alcoholism. Manage the microarray facility (Center for Medical Genomics), provide statistical and bioinformatics analysis for microarray customers. Tertiary analysis of RNA seq and DNA seq.
April 2006 - present
Indiana University School of Medicine
Position
  • Assistant Research Professor
Description
  • Edenberg lab - Genetics of Alcoholism Center for Medical Genomics - core facility that provides Next Gen sequencing, microarrays and genotyping.
Education
September 1998 - April 2006
Indiana University School of Medicine
Field of study
  • Medical and Molecular Genetics
August 1978 - August 1984

Publications

Publications (120)
Article
Full-text available
Aberrant connectivity of large-scale brain networks has been observed among individuals with alcohol use disorders (AUDs) as well as in those at risk, suggesting deficits in neural communication between brain regions in the liability to develop AUD. Electroencephalographical (EEG) coherence, which measures the degree of synchrony between brain regi...
Article
Fibroblast Growth Factor 23 (FGF23) is a bone-derived hormone that reduces kidney phosphate reabsorption and 1,25(OH)2 vitamin D synthesis via its required co-receptor alpha-Klotho. To identify novel genes that could serve as targets to control FGF23-mediated mineral metabolism, gene array and single-cell RNA sequencing were performed in wild type...
Article
Full-text available
Background Variation in liability to cannabis use disorder has a strong genetic component (estimated twin and family heritability about 50–70%) and is associated with negative outcomes, including increased risk of psychopathology. The aim of the study was to conduct a large genome-wide association study (GWAS) to identify novel genetic variants ass...
Article
Full-text available
To provide insights into the biology of opioid dependence (OD) and opioid use (i.e., exposure, OE), we completed a genome-wide analysis comparing 4503 OD cases, 4173 opioid-exposed controls, and 32,500 opioid-unexposed controls, including participants of European and African descent (EUR and AFR, respectively). Among the variants identified, rs9291...
Article
Full-text available
Ethanol exposure during prenatal development causes fetal alcohol spectrum disorder (FASD), the most frequent preventable birth defect and neurodevelopmental disability syndrome. The molecular targets of ethanol toxicity during development are poorly understood. Developmental stages surrounding gastrulation are very sensitive to ethanol exposure. T...
Article
Cycles of heavy drinking and abstinence can lead to ethanol abuse disorder. We studied the effects of chronic intermittent ethanol exposure (CIE) over three weeks on neuroblastoma cells, using an ethanol concentration frequently attained in binge drinking (40 mM, 184 mg/dl). There were many changes in gene expression but most were small. CIE affect...
Article
High serum concentrations of kidney-derived protein uromodulin [Tamm-Horsfall protein (THP)] have recently been shown to be independently associated with low mortality in both older adults and cardiac patients, but the underlying mechanism remains unclear. Here, we show that THP inhibits the generation of reactive oxygen species (ROS) both in the k...
Article
The short-term effects of alcohol on gene expression in brain tissue cannot directly be studied in humans. Because neuroimmune signaling is altered by alcohol, immune cells are a logical, accessible choice to study and may provide biomarkers. RNAseq was used to study the effects of 48-h exposure to ethanol on lymphoblastoid cell lines (LCLs) from 2...
Article
Full-text available
Alcohol exposure triggers changes in gene expression and biological pathways in human brain. We explored alterations in gene expression in the Pre-Frontal Cortex (PFC) of 65 alcoholics and 73 controls of European descent, and identified 129 genes that showed altered expression (FDR < 0.05) in subjects with alcohol dependence. Differentially express...
Article
The Collaborative Study on the Genetics of Alcoholism (COGA) has focused on studies of large families with multiple alcoholic members. We have conducted genome-wide association studies (GWAS) to identify common variants that affect risk for alcohol dependence and related phenotypes, including electrophysiological endophenotypes. Because we have stu...
Preprint
Full-text available
Alcohol exposure triggers changes in gene expression and biological pathways in human brain. We explored alterations in gene expression in the Pre-Frontal Cortex (PFC) of 65 alcoholics and 73 controls of European descent, and identified 129 genes that showed altered expression (FDR < 0.05) in subjects with alcohol dependence. Differentially express...
Article
Full-text available
Liability to alcohol dependence (AD) is heritable, but little is known about its complex polygenic architecture or its genetic relationship with other disorders. To discover loci associated with AD and characterize the relationship between AD and other psychiatric and behavioral outcomes, we carried out the largest genome-wide association study to...
Article
Alcohol use disorders (AUD) are complex traits, meaning that variations in many genes contribute to the risk, as does the environment. Although the total genetic contribution to risk is substantial, most individual variations make only very small contributions. By far the strongest contributors are functional variations in two genes involved in alc...
Preprint
Full-text available
Liability to alcohol dependence (AD) is heritable, but little is known about its complex polygenic architecture or its genetic relationship with other disorders. To discover loci associated with AD and characterize the relationship between AD and other psychiatric and behavioral outcomes, we carried out the largest GWAS to date of DSM - IV diagnose...
Article
Full-text available
Preconditioning with a low dose of endotoxin confers unparalleled protection against otherwise lethal models of sepsis. The mechanisms of preconditioning have been investigated extensively in isolated immune cells such as macrophages. However, the role of tissue in mediating the protective response generated by preconditioning remains unknown. Here...
Article
Binge drinking of alcohol during adolescence is a serious public health concern with long-term consequences, including decreased hippocampal and prefrontal cortex volume and defects in memory. We used RNA sequencing to assess the effects of adolescent binge drinking on gene expression in these regions. Male adolescent alcohol-preferring (P) rats we...
Article
Full-text available
17β-estradiol (E2) exerts complex and context-dependent effects in pulmonary hypertension. In hypoxia-induced pulmonary hypertension (HPH), E2 attenuates lung vascular remodeling through estrogen receptor (ER)-dependent effects; however, ER target genes in the hypoxic lung remain unknown. In order to identify the genome regulated by the E2-ER axis...
Chapter
Full-text available
The purpose of this review is to present up-to-date pharmacological, genetic, and behavioral findings from the alcohol-preferring P rat and summarize similar past work. Behaviorally, the focus will be on how the P rat meets criteria put forth for a valid animal model of alcoholism with a highlight on its use as an animal model of polysubstance abus...
Article
Objective: Following vascular injury medial smooth muscle cells dedifferentiate and migrate through the internal elastic lamina where they form a neointima. The goal of the current study was to identify changes in gene expression that occur prior to the development of neointima and are associated with the early response to injury. Approach and Res...
Article
Background: This study investigated the effect of lithium monotherapy on peripheral lymphocyte gene expression in bipolar disorder (BD). Method: Twenty-two medication-free bipolar subjects (11 hypomanic, 11 depressed) were started on lithium monotherapy. Closely matched healthy subjects (n = 15) were included as controls but did not receive trea...
Article
Full-text available
This study tested the hypothesis that obesity alters the cardiac response to ischemia/reperfusion and/or glucagon like peptide-1 (GLP-1) receptor activation, and that these differences are associated with alterations in the obese cardiac proteome and microRNA (miRNA) transcriptome. Ossabaw swine were fed normal chow or obesogenic diet for 6 months....
Article
Background: Binge drinking of alcohol during adolescence is a serious public health concern with long-term consequences, including increased pain, fear, and anxiety. The periaqueductal gray (PAG) is involved in processing pain, fear, and anxiety. The effects of adolescent binge drinking on gene expression in this region have yet to be studied. Me...
Article
Full-text available
Herein, we have reviewed the role of glutamate, the major excitatory neurotransmitter in the brain, in a number of neurochemical, -physiological, and -behavioral processes mediating the development of alcohol dependence. The findings discussed include results from both preclinical as well as neuroimaging and postmortem clinical studies. Expression...
Article
Full-text available
Herein, we have reviewed the role of glutamate, the major excitatory neurotransmitter in the brain, in a number of neurochemical, -physiological, and -behavioral processes mediating the development of alcohol dependence. The findings discussed include results from both preclinical as well as neuroimaging and postmortem clinical studies. Expression...
Article
Full-text available
Vascular calcification is a complex process and has been associated with aging, diabetes, chronic kidney disease (CKD). Although there have been several studies that examine the role of miRNAs (miRs) in bone osteogenesis, little is known about the role of miRs in vascu-lar calcification and their role in the pathogenesis of vascular abnormalities....
Article
Full-text available
Adult antisocial behavior (AAB) is moderately heritable, relatively common and has adverse consequences for individuals and society. We examined the molecular genetic basis of AAB in 1379 participants from a case-control study in which the cases met criteria for alcohol dependence. We also examined whether genes of interest were expressed in human...
Article
Full-text available
Pachymic acid (PA) is a purified triterpene extracted from medicinal fungus Poria cocos. In this paper, we investigated the anticancer effect of PA on human chemotherapy resistant pancreatic cancer. PA triggered apoptosis in gemcitabine-resistant pancreatic cancer cells PANC-1 and MIA PaCa-2. Comparative gene expression array analysis demonstrated...
Article
Intrauterine exposure to gestational diabetes mellitus (GDM) is linked to development of hypertension, obesity, and type 2 diabetes in children. Our previous studies determined that endothelial colony forming cells (ECFCs) from neonates exposed to GDM exhibit impaired function. The current goals were to identify aberrantly expressed genes that cont...
Article
Full-text available
Phosphodiesterase-4 (PDE4) and neuroimmune signaling have been posited to regulate alcohol drinking. This study evaluated the involvement of PDE4 and Il22ra2 on ethanol (EtOH) intake by alcohol-preferring (P) and high-alcohol-drinking (HAD1) rats. Exp 1 determined the dose-response effects of PDE4 inhibitors, rolipram, and Ro 20-1724, on 2 h/day fr...
Article
To elucidate the effects of a controlled exposure to ethanol on gene expression, we studied lymphoblastoid cell lines (LCLs) from 21 alcoholics and 21 controls. We cultured each cell line for 24 h with and without 75 mM ethanol and measured gene expression using microarrays. Differences in expression between LCLs from alcoholics and controls includ...
Article
Full-text available
Disruption of protein folding in the endoplasmic reticulum triggers the Unfolded Protein Response (UPR), a transcriptional and translational control network designed to restore protein homeostasis. Central to the UPR is PERK phosphorylation of the α subunit of eIF2 (eIF2α∼P), which represses global translation coincident with preferential translati...
Article
Full-text available
Fetal alcohol spectrum disorder (FASD) occurs when pregnant mothers consume alcohol, causing embryonic ethanol exposure and characteristic birth defects that include craniofacial, neural and cardiac defects. Gastrulation is a particularly sensitive developmental stage for teratogen exposure, and zebrafish is an outstanding model to study gastrulati...
Article
The chronic high-level alcohol consumption seen in alcoholism leads to dramatic effects on the hippocampus, including decreased white matter, loss of oligodendrocytes and other glial cells, and inhibition of neurogenesis. Examining gene expression in post mortem hippocampal tissue from 20 alcoholics and 19 controls allowed us to detect differential...
Article
Full-text available
Analysis of global gene expression in mesenteric control and collateral arteries was used to investigate potential molecules, pathways, and mechanisms responsible for impaired collateral growth in the Spontaneously Hypertensive Rat (SHR). A fundamental difference was observed in overall gene expression pattern in SHR versus Wistar Kyoto (WKY) colla...
Article
Full-text available
Environmental stresses that disrupt protein homeostasis induce phosphorylation of eIF2, triggering repression of global protein synthesis coincident with preferential translation of ATF4, a transcriptional activator of the Integrated Stress Response (ISR). Depending on the extent of protein disruption, ATF4 may not be able to restore proteostatic c...
Article
Full-text available
Cortical–striatal circuit dysfunction in mental illness may enhance addiction vulnerability. Neonatal ventral hippocampal lesions (NVHL) model this dual diag-nosis causality by producing a schizophrenia syn-drome with enhanced responsiveness to addictive drugs. Rat genome-wide microarrays containing >24 000 probesets were used to examine separate a...
Article
Several studies have identified genes associated with alcohol use disorders, but the variation in each of these genes explains only a small portion of the genetic vulnerability. The goal of the present study was to perform a genome-wide association study (GWAS) in extended families from the Collaborative Study on the Genetics of Alcoholism (COGA) t...
Article
Vascular risk factors characterized by oxidative stress are correlated with impaired collateral growth through mechanisms largely unknown. Spontaneously hypertensive rats (SHR) with increased oxidative stress were used to investigate potential mechanisms mediating impaired collateral compensation. Microarray analysis of global gene expression was p...
Article
Full-text available
Disruptions of the endoplasmic reticulum (ER) that perturb protein folding cause ER stress and elicit an unfolded protein response (UPR) that involves translational and transcriptional changes in gene expression aimed at expanding the ER processing capacity and alleviating cellular injury. Three ER stress sensors (PERK, ATF6, and IRE1) implement th...
Article
Full-text available
This study was performed to discover prognostic genomic markers associated with postoperative outcome of stage I to III non-small cell lung cancer (NSCLC) that are reproducible between geographically distant and demographically distinct patient populations. American patients (n = 27) were stratified on the basis of recurrence and microarray profili...
Data
GO gene sets selected by keywords. List of gene sets used in GSEA analyses, derived from GO categories selected by key words for Early Development. Title of each set followed by Entrez Gene Ids of the genes in the set.
Data
Keyword and GO categories. List of keywords used and the GO categories identified by these key words for Early Development.
Data
GO categories related to Stem Cells. Gene sets used in GSEA analysis based on GO categories related to Stem Cells. Title of each set followed by Entrez Gene Ids of the genes in the set.
Article
Full-text available
We have previously demonstrated that alcohol exposure at early neurulation induces growth retardation, neural tube abnormalities, and alteration of DNA methylation. To explore the global gene expression changes which may underline these developmental defects, microarray analyses were performed in a whole embryo mouse culture model that allows contr...
Data
Microarray dataset of differential gene expression in wild-type and ΔGCN5-A parasites grown in alkaline pH (8.2) or control (pH 7.0) medium for three days. Data for three p values (0.001, 0.01, and 0.05) are provided. (2.49 MB XLS)
Data
Transcripts that are induced >2-fold in Toxoplasma grown in alkaline medium. (0.06 MB PDF)
Data
Full-text available
Hypothetical genes up-regulated during alkaline pH stress in Toxoplasma (p<0.001). (0.01 MB PDF)
Data
List of primers used in this study. (0.01 MB PDF)