A5015603733- Pancreatic function and diabetes
- Regulation of Appetite and Obesity
- GDF15 and Related Biomarkers
- Circadian rhythm and melatonin
- Biochemical Analysis and Sensing Techniques
- Nutrition and Health in Aging
- Adipose Tissue and Metabolism
- Genetics and Neurodevelopmental Disorders
- CRISPR and Genetic Engineering
- Sleep and Wakefulness Research
- Adipokines, Inflammation, and Metabolic Diseases
- Bipolar Disorder and Treatment
- Diet and metabolism studies
- Nuclear Receptors and Signaling
- Endoplasmic Reticulum Stress and Disease
- Neuroendocrine regulation and behavior
- Hypothalamic control of reproductive hormones
- Diabetes and associated disorders
- Patient Satisfaction in Healthcare
- Neuroscience and Neural Engineering
- Olfactory and Sensory Function Studies
- Genetic Syndromes and Imprinting
- Macrophage Migration Inhibitory Factor
- Aging and Gerontology Research
- Calcium signaling and nucleotide metabolism
University of Michigan–Ann Arbor
2018-2025
McGill University
2023-2025
McGill University Health Centre
2024
Marche Polytechnic University
2023
Ann Arbor Center for Independent Living
2018-2020
British Columbia Children's Hospital
2012-2018
University of British Columbia
2013-2018
Child and Family Research Institute
2012-2015
Sunny Hill Health Centre for Children
2012
Wayne State University
1972-1973
Personal age (how old a person seems to himself) is proposed (a) as potential component of total functional and (b) basis classification in attempts create modify “old behavior.” Companion constructs are those interpersonal others) consensual (degree agreement between personal ages). Illustrative data reported from sample 75 adults (38 women, 37 men) who range 20 69; 43 enrolled advanced gerontology training programs. The results suggest that comprised at least two fairly distinct...
Significance Growth and differentiation factor-15 (GDF-15) acts through its receptor, GFRAL, expressed within the area postrema to reduce food intake body weight. However, we do not yet understand GFRAL neuron transcriptional profile, regulation, direct downstream target sites of neurons, or necessary cell types required for GDF-15 activity. Herein, identify genetic signature neurons show that these cells are positively regulated by a number aversive stimuli, project both nucleus solitary...
Infradian mood and sleep-wake rhythms with periods of 48 hours beyond have been observed in patients bipolar disorder (BD), which even persist the absence exogenous timing cues, indicating an endogenous origin. Here, we show that mice exposed to methamphetamine drinking water develop infradian locomotor extend sleep length manic state–associated behaviors support a model for cycling BD. The capacity is abrogated upon genetic disruption dopamine (DA) production DA neurons ventral tegmental...
To identify neurons that specifically increase blood glucose from among the diversely functioning cell types in ventromedial hypothalamic nucleus (VMN), we studied cholecystokinin receptor B–expressing (CCKBR-expressing) VMN targets of glucose-elevating parabrachial neurons. Activation these VMNCCKBR increased glucose. Furthermore, although silencing broader decreased energy expenditure and promoted weight gain without altering levels, hIepatic production, insulin-independently decreasing...
Abstract Amylin analogs, including potential anti-obesity therapies like cagrilintide, act on neurons in the brainstem dorsal vagal complex (DVC) that express calcitonin receptors (CALCR). These receptors, often combined with receptor activity-modifying proteins (RAMPs), mediate suppression of food intake and body weight. To understand molecular neural mechanisms cagrilintide action, we used single-nucleus RNA sequencing to define 89 cell populations across rat, mouse, non-human primate...
The ventromedial hypothalamic nucleus (VMH) controls diverse behaviors and physiologic functions, suggesting the existence of multiple VMH neural subtypes with distinct functions. Combing translating ribosome affinity purification RNA-sequencing (TRAP-seq) data single-nucleus (snRNA-seq) data, we identified 24 mouse neuron clusters. Further analysis, including snRNA-seq from macaque tissue, defined a more tractable parceling scheme consisting six major genetically anatomically differentiated...
Cellular homeostasis requires intrinsic sensing mechanisms to temper function in the face of prolonged activity. In pancreatic β-cell, glucose is likely a physiological trigger that activates an adaptive response stimulation, thereby maintaining cellular homeostasis. Immediate early genes (IEGs) are activated as first line defense and largely responsible for transmitting environmental cue response. Here we examine regulation novel β-cell IEG, neuronal PAS domain protein 4 (Npas4). Using MIN6...
Leptin acts via its receptor LepRb on specialized neurons in the brain to modulate food intake, energy expenditure, and body weight. activates signal transducers activators of transcription (STATs, including STAT1, STAT3, STAT5) control gene expression. Because STAT3 is crucial for physiologic leptin action, we used TRAP-seq examine expression mice ablated Stat3 (Stat3LepRbKO mice), revealing STAT3-dependent transcriptional targets leptin. To understand roles STAT proteins also STAT1 or...
While Cre-dependent viral systems permit the manipulation of many neuron types, some cell populations cannot be targeted by a single DNA recombinase. Although combined use Flp and Cre recombinases can overcome this limitation, insufficient recombinase activity reduce efficacy existing Cre+Flp-dependent systems. We developed sensitive dual recombinase-activated approach: tTA-driven Recombinase-Guided Intersectional Targeting (tTARGIT) adeno-associated viruses (AAVs). tTARGIT AAVs utilize...
Healthcare-associated infections (HAIs) and antimicrobial resistance (AMR) are serious health challenges. Point prevalence surveys (PPSs) valuable tools for monitoring HAIs AMR.To describe results of the ECDC PPS 2022 dealing with HAIs, consumption, associated factors, in acute care hospitals.The survey was performed November 14 hospitals according to protocol proposed by European Centre Disease Prevention Control. Multilevel logistic regression using geographical area/hospital type as...
Depolarization of neuroendocrine cells results in calcium influx, which induces vesicle exocytosis and alters gene expression. These processes, along with the restoration resting membrane potential, are energy intensive. We hypothesized that cellular mechanisms exist to maximize production during excitation. Here, we demonstrate NPAS4, an immediate early basic helix-loop-helix (bHLH)-PAS transcription factor, acts by suppressing hypoxia-inducible factor 1α (HIF1α). As such, knockout Npas4...
Second-generation antipsychotics (SGAs) are commonly prescribed to youth but associated with metabolic effects including obesity and diabetes. The mechanisms underlying diabetes development unclear. purpose of this study was compare glucose homeostasis, insulin sensitivity, secretion, overall β-cell function in risperidone-treated, quetiapine-treated, SGA-naive mental illness. We conducted a cross-sectional which aged 9 18 years underwent 2-hour oral tolerance test. Indices for sensitivity...
Leptin acts via its receptor, LepRb, on specialized neurons in the brain to modulate energy balance and glucose homeostasis. LepRb→STAT3 signaling plays a crucial role leptin action, but LepRb also mediates an additional as-yet-unidentified signal (Signal 2) that is important for action. Signal 2 requires regions addition those required JAK2 activation operates independently of STAT3 phosphorylation sites. To identify sequences mediate 2, we used CRISPR/Cas9 generate five novel mouse lines...
ABSTRACT: The Do‐It‐Yourself Death Certificate (DIYDC) is a slightly abridged facsimile of the Michigan death certificate. In its first series research applications, DIYDC was administered to 158 subjects who had chosen death‐related courses or occupations; other questionnaires were also administered. Among findings: (a) by cancer markedly underestimated; (b) quick heavily preferred; and (c) measure proportion‐of‐life‐remaining helpful in differentiating preferences for mode body disposal...
Growth differentiation factor 15 (GDF15), a TGFβ superfamily cytokine, acts through its receptor, cell line-derived neurotrophic factorfamily receptor α-like (GFRAL), to suppress food intake and promote nausea. GDF15 is broadly expressed at low levels but increases in states of disease such as cancer, cachexia, sepsis. Whether necessary for inducing sepsis-associated anorexia body weight loss currently unclear. To test this we used model moderate systemic infection GDF15KO GFRALKO mice with...
The dorsal vagal complex (DVC) is a region in the brainstem comprised of an intricate network specialized cells responsible for sensing and propagating many appetite-related cues. Understanding dynamics controlling appetite requires deeply exploring cell types transitory states harbored this brain site. We generated multi-species DVC atlas using single nuclei RNAseq (sn-RNAseq), thorough curation harmonization mouse rat data which includes >180,000 123 identities at 5 granularities...
The TGF-β cytokine, growth differentiation factor 15 (GDF15) is a critical mediator of the physiologic response to range cellular stresses. While circulating levels GDF15 are normally very low, these increase substantially under number acute and chronic pathogenic states including mycotoxin exposure, infection cancer. controls outputs reduced appetite, gastric motility, hyperalgesia, emesis, energy expenditure immune cell function via GDNF family receptor alpha-like (GFRAL). area postrema...
Abstract To determine the function and mechanisms of action for hindbrain neurons that express GFRAL, receptor anorexigenic peptide, GDF-15, we generated Gfral cre conditional CreERT mice. While signals infection or pathophysiologic states (rather than meal ingestion) stimulate GFRAL neurons, artificial activation Cre - expressing inhibited feeding, decreased gastric emptying, promoted a conditioned taste aversion (CTA). Additionally, smaller population captured by allele emptying produced...
Deoxynivalenol (DON), a type B trichothecene mycotoxin contaminating grain, promotes nausea, emesis, and anorexia. With DON exposure, circulating levels of intestinally derived satiation hormones, including glucagon-like peptide 1 (GLP-1), are elevated. To directly test whether GLP-1 signaling mediates the effects DON, we examined response or GLP-1R-deficient mice to injection. We found comparable anorectic conditioned taste avoidance learning responses in GLP-1/GLP-1R-deficient compared...