Jeffrey F. Waring
A5091020033- Gene expression and cancer classification
- Alzheimer's disease research and treatments
- Epigenetics and DNA Methylation
- Computational Drug Discovery Methods
- Bioinformatics and Genomic Networks
- Genetic Associations and Epidemiology
- Cytokine Signaling Pathways and Interactions
- Dementia and Cognitive Impairment Research
- Protein Tyrosine Phosphatases
- Pharmacogenetics and Drug Metabolism
- Drug Transport and Resistance Mechanisms
- Molecular Biology Techniques and Applications
- Drug-Induced Hepatotoxicity and Protection
- Hepatitis C virus research
- Chronic Lymphocytic Leukemia Research
- Nicotinic Acetylcholine Receptors Study
- Receptor Mechanisms and Signaling
- Cholinesterase and Neurodegenerative Diseases
- interferon and immune responses
- Acute Myeloid Leukemia Research
- HIV Research and Treatment
- Neuroscience and Neuropharmacology Research
- HIV/AIDS drug development and treatment
- Metabolism, Diabetes, and Cancer
- Genomics and Rare Diseases
AbbVie (United States)
2015-2024
Abbott Fund
2003-2012
Abbott (United States)
2002-2012
Abbott (United Kingdom)
2006-2011
Children's Hospital of Eastern Ontario
2008
Cleveland Clinic
2007
Michigan State University
2005-2006
University of Minnesota System
2001
Institute of Human Genetics
2001
Cancer Research UK Manchester Institute
1999
The cellular inhibitor of apoptosis 1 and 2 (cIAP1 cIAP2) proteins have been implicated in the activation NF-kappaB by TNFalpha; however, genetic deletion either cIAP1 or did not support a physiologically relevant role, perhaps because functional redundancy. To address this, we used combined siRNA knockdown approaches report that are indeed critical, yet redundant, regulators upon TNFalpha treatment. Whereas was properly activated cultured primary cells deficient 2, removal both cIAPs...
The role of protein-tyrosine phosphatase 1B (PTP1B) in diabetes was investigated using an antisense oligonucleotide ob / and db mice. PTP1B treatment normalized plasma glucose levels, postprandial excursion, HbA 1C . Hyperinsulinemia also reduced with improved insulin sensitivity. protein mRNA were liver fat no effect skeletal muscle. Insulin signaling proteins, receptor substrate 2 phosphatidylinositol 3 (PI3)-kinase regulatory subunit p50α, increased PI3-kinase p85α expression decreased...
Abstract Understanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases (CVDs). Here, we perform genome-wide association analyses 141 species (n = 2,181 individuals), followed by phenome-wide scans with 25 CVD related phenotypes 511,700 individuals). We identify 35 lipid-species-associated loci (P <5 ×10 −8 ), 10 which associate risk including five new loci- COL5A1 , GLTPD2 SPTLC3 MBOAT7 GALNT16 (false...
A genetic contribution to preeclampsia susceptibility has been established but is still incompletely understood.To disentangle the underlying architecture of and or other maternal hypertension during pregnancy with a genome-wide association study (GWAS) hypertensive disorders pregnancy.This GWAS included meta-analyses in combination phenotype encompassing disorders. Two overlapping groups were selected for examination, namely, pregnancy. Data from Finnish Genetics Pre-eclampsia Consortium...
Prioritization of compounds based on human hepatotoxicity potential is currently a key unmet need in drug discovery, as it can become major problem for several lead later stages the discovery pipeline. The authors report validation and implementation high-content multiparametric cytotoxicity assay simultaneous measurement 8 cell health indicators associated with nuclear morphology, plasma membrane integrity, mitochondrial function, proliferation. Compounds are prioritized by (a) computing an...
Abstract Polygenic risk scores (PRS) for breast cancer have potential to improve prediction, but there is limited information on their utility in various clinical situations. Here we show that among 122,978 women the FinnGen study with 8401 cases, PRS modifies of two high-impact frameshift variants. Similarly, after diagnosis, individuals elevated an developing contralateral cancer, and can considerably assessment female first-degree relatives. In more detail, c.1592delT variant PALB2...
Abstract Background Alzheimer’s disease (AD) is a chronic progressive neurodegenerative impacting an estimated 44 million adults worldwide. The causal pathology of AD (accumulation amyloid-beta and tau), precedes hallmark symptoms dementia by more than decade, necessitating development early diagnostic markers onset, particularly for new drugs that aim to modify processes. To evaluate differentially methylated positions (DMPs) as novel blood-based biomarkers AD, we used subset 653...
Abstract Background Identifying biomarkers associated with Alzheimer’s disease (AD) progression may enable patient enrichment and improve clinical trial designs. Epigenome-wide association studies have revealed correlations between DNA methylation at cytosine-phosphate-guanine (CpG) sites AD pathology diagnosis. Here, we report relationships peripheral blood profiles measured using Infinium® MethylationEPIC BeadChip in participants from the Disease Neuroimaging Initiative (ADNI) cohort....
Narcolepsy type 1 (NT1) is caused by a loss of hypocretin/orexin transmission. Risk factors include pandemic 2009 H1N1 influenza A infection and immunization with Pandemrix®. Here, we dissect disease mechanisms interactions environmental triggers in multi-ethnic sample 6,073 cases 84,856 controls. We fine-mapped GWAS signals within HLA (DQ0602, DQB1*03:01 DPB1*04:02) discovered seven novel associations (CD207, NAB1, IKZF4-ERBB3, CTSC, DENND1B, SIRPG, PRF1). Significant at TRA DQB1*06:02 loci...
PURPOSE Family history (FH) and pathogenic variants (PVs) are used for guiding risk surveillance in selected high-risk women but little is known about their impact breast cancer screening on population level. In addition, polygenic scores (PRSs) have been shown to efficiently stratify through combining information common genetic factors into one measure. METHODS longitudinal real-life data, we evaluate PRS, FH, PVs stratified screening. Using FinnGen (N = 117,252), linked the Mass Screening...
Protein tyrosine phosphatase 1B (PTP1B) has been implicated as a negative regulator of insulin action. Overexpression PTP1B protein observed in insulin-resistant states associated with obesity. Mice lacking functional gene exhibit increased sensitivity and are resistant to weight gain. To investigate the role adipose tissue from obese animals, hyperglycemic (ob/ob) mice were treated antisense oligonucleotide (ISIS-113715). A significant reduction adiposity correlated decrease levels fat....
Idiosyncratic adverse drug reactions (IADRs) represent an important human health problem, yet animal models for preclinical prediction of these are lacking. Recent evidence in animals suggests that some IADRs arise from interaction with inflammatory episode renders the liver sensitive to injury. Diclofenac (DCLF) is one those drugs which clinical use limited by idiosyncratic We tested hypothesis modest inflammation triggered rats a small dose lipopolysaccharide (LPS) nonhepatotoxic DCLF...
Isolated primary human hepatocytes are a well accepted system for evaluating pharmacological and toxicological effects in humans. However, questions remain regarding how culturing affects the liver-specific functions of hepatocytes. In addition, cryopreservation could also potentially affect differentiation state The first aim present study was to compare gene expression freshly isolated that liver origin evaluate changes occurring after cryopreservation/thawing, both when maintained...
Idiosyncratic drug toxicity refers to toxic reactions occurring in a small subset of patients and usually cannot be predicted during preclinical or early phases clinical trials. One hypothesis for the pathogenesis hepatic idiosyncratic is that, certain individuals, underlying inflammation results sensitization liver, such that injury occurs from an agent typically would not cause hepatotoxicity at therapeutic dose. We explored this possibility by cotreating rats with nonhepatotoxic doses...
The effectiveness of IFN-alpha2b for human multiple myeloma has been variable. TRAIL proposed to mediate apoptosis in myeloma. In this study we assessed the effects signaling on apoptotic activity and cell survival. While was one most potently induced proapoptotic genes cells following treatment, less than 20% underwent apoptosis. Thus, hypothesized that an IFN-stimulated gene (ISG) with prosurvival might suppress TRAIL-mediated Consistent this, stabilized mitochondria inhibited caspase-3...
BACKGROUND: Adverse pregnancy outcomes (APO) contribute to higher risk of maternal cerebrovascular disease, but longitudinal data that include APO and stroke timing are lacking. We hypothesized associated with younger age at first stroke, a stronger relationship in those >1 APO. METHODS: analyzed Finnish nationwide health registry from the FinnGen Study. included women who gave birth after 1969 when hospital discharge was established. defined as affected by gestational hypertension,...
Abstract Background Limited understanding of the diversity variants in cystic fibrosis transmembrane conductance regulator ( CFTR ) gene across ancestries hampers efforts to advance molecular diagnosis (CF). The consequences pose a risk delayed diagnoses and subsequently worsened health outcomes for patients. Therefore, characterizing spectrum is critical revolutionizing CF. Methods We analyzed 454,727 UK Biobank (UKBB) whole-exome sequences characterize ancestries. Using PanUKBB...