A5072397213- Bone health and treatments
- Fibroblast Growth Factor Research
- Pancreatic function and diabetes
- Bone Metabolism and Diseases
- Metabolism, Diabetes, and Cancer
- Adipose Tissue and Metabolism
- dental development and anomalies
- Erythrocyte Function and Pathophysiology
- Cancer-related Molecular Pathways
- Diabetes and associated disorders
- Immune Cell Function and Interaction
- RNA and protein synthesis mechanisms
- Herpesvirus Infections and Treatments
- Animal Genetics and Reproduction
- Liver Disease Diagnosis and Treatment
- Phagocytosis and Immune Regulation
- Digestive system and related health
- Cancer, Hypoxia, and Metabolism
- Drug Transport and Resistance Mechanisms
- DNA and Nucleic Acid Chemistry
- Peripheral Neuropathies and Disorders
- Neuropeptides and Animal Physiology
- Genomics and Chromatin Dynamics
- Hair Growth and Disorders
- Diet, Metabolism, and Disease
Yale University
2015-2025
Yale Cancer Center
2022-2024
University of New Haven
2024
Baylor University
2022
University of Colorado Anschutz Medical Campus
2022
UCB Pharma (United States)
2022
CARE USA
2022
University School
2021
IQVIA (United Kingdom)
2000
McGill University
1998
Parathyroid hormone-related peptide (PTHrP) was initially identified as a product of malignant tumors that mediates paraneoplastic hypercalcemia. It is now known the parathyroid hormone (PTH) and PTHrP genes are evolutionarily related products these two share common receptor, PTH/PTHrP receptor. receptor widely expressed in both adult fetal tissues, recent gene-targeting disruption experiments have implicated developmental regulatory molecule. Apparent functions include regulation...
OBJECTIVE Insulin resistance is a major characteristic of type 2 diabetes and causally associated with obesity. Inflammation plays an important role in obesity-associated insulin resistance, but the underlying mechanism remains unclear. Interleukin (IL)-10 anti-inflammatory cytokine lower circulating levels obese subjects, acute treatment IL-10 prevents lipid-induced resistance. We examined glucose homeostasis using transgenic mice muscle-specific overexpression (MCK-IL10). RESEARCH DESIGN...
The MYC oncogene is frequently mutated and overexpressed in human renal cell carcinoma (RCC). However, there have been no studies on the causative role of or any other initiation maintenance kidney tumorigenesis. Here, we show through a conditional transgenic mouse model that oncogene, but not RAS initiates maintains RCC. Desorption electrospray ionization-mass-spectrometric imaging was used to obtain chemical maps metabolites lipids RCC samples. Gene expression analysis revealed tumors...
Nonalcoholic fatty liver disease (NAFLD) is a risk factor for type 2 diabetes (T2D), but whether NAFLD plays causal role in the pathogenesis of T2D uncertain. One proposed mechanism linking to hepatic insulin resistance involves diacylglycerol-mediated (DAG-mediated) activation protein kinase C-ε (PKCε) and consequent inhibition receptor (INSR) activity. However, molecular underlying PKCε INSR activity unknown. Here, we used mass spectrometry identify phosphorylation site Thr1160 as...
Parathyroid hormone–related peptide (PTHrP) appears to play a major role in skeletal development. Targeted disruption of the PTHrP gene mice causes dysplasia with accelerated chondrocyte maturation (Amizuka, N., H. Warshawsky, J.E. Henderson, D. Goltzman, and A.C. Karaplis. 1994. J. Cell Biol. 126:1611–1623; Karaplis, A.C., A. Luz, Glowacki, R.T. Bronson, V.L.J. Tybulewicz, H.M. Kronenberg, R.C. Mulligan. Genes Dev. 8: 277–289). A constitutively active mutant PTH/PTHrP receptor has been...
ABSTRACT Parathyroid hormone-related protein (PTHrP) was originally discovered as a tumor product that causes humoral hypercalcemia of malignancy. PTHrP is now known to be widely expressed in normal tissues and growing evidence suggests it an important developmental regulatory molecule. We had previously reported overexpression the mammary glands transgenic mice impaired branching morphogenesis during sexual maturity early pregnancy. demonstrate plays critical role epithelial-mesenchymal...
Parathyroid hormone (PTH)-related protein (PTHrP)-knockout mice die at birth with a chondrodystrophic phenotype characterized by premature chondrocyte differentiation and accelerated bone formation, whereas overexpression of PTHrP in the chondrocytes transgenic produces delay maturation endochondral ossification. Replacement expression PTHrP-knockout using procollagen II-driven transgene results correction lethal skeletal abnormalities generates animals that are effectively PTHrP-null all...
We report the identification of βIV spectrin, a novel spectrin isolated as an interactor receptor tyrosine phosphatase-like protein ICA512. The gene is located on human and mouse chromosomes 19q13.13 7b2, respectively. Alternative splicing generates at least four distinct isoforms, numbered βIVΣ1–βIVΣ4 spectrin. longest isoform (βIVΣ1 spectrin) includes actin-binding domain, followed by 17 repeats, specific domain in which amino acid sequence ERQES repeated times, several putative...
Hepatocyte growth factor (HGF) is produced in pancreatic mesenchyme-derived cells and islet cells. <i>In vitro</i>, HGF increases the insulin content proliferation of islets. To study role <i>in vivo</i>, we have developed three lines transgenic mice overexpressing mHGF using rat II promoter (RIP). Each RIP-HGF line displays clear expression mRNA protein islet. RIP-mHGF are relatively hypoglycemic post-prandial fasting states compared with their normal littermates. They display inappropriate...
Transplantation of human hematopoietic stem cells into severely immunocompromised newborn mice allows the development a and immune system in vivo. NOD/scid/γ c −/− (NSG) BALB/c Rag2 γ are most commonly used mouse strains for this purpose number studies have demonstrated high value these model systems areas spanning from basic to translational research. However, limited cross-reactivity many murine cytokines on residual host function against xenogeneic grafts results defective maintenance...
Parathyroid hormone-related peptide (PTHrP) was initially discovered as the cause of syndrome humoral hypercalcemia malignancy. Subsequently, PTHrP gene has been shown to be expressed in a wide variety normal tissues, including skin. Because biological function skin remains unknown, we used human keratin 14 promoter target overexpression transgenic mice. We achieved 10-fold level skin, and promoter-PTHrP mice displayed disturbance hair follicle development. These either failed initiate...
ABSTRACT Parathyroid hormone-related protein (PTHrP) was originally discovered as the tumor product that causes humoral hypercalcemia of malignancy. PTHrP is now known to be widely expressed in many normal fetal tissues where it may participate regulation organogenesis. In this report, we document overexpression myoepithelial cells mammary glands transgenic mice resulted a form breast hypoplasia characterized by profound defect branching morphogenesis developing duct system. addition,...
Autoantibodies targeting the acetylcholine receptor (AChR), found in patients with myasthenia gravis (MG), mediate pathology through 3 mechanisms: complement-directed tissue damage, blocking of binding site, and internalization AChR. Clinical assays, used to diagnose monitor patients, measure only autoantibody binding. Consequently, they are limited providing association disease burden, understanding mechanistic heterogeneity, monitoring therapeutic response. The objective this study was...
Abstract Prior reports have demonstrated that both parathyroid hormone-related protein (PTHrP) and the type I PTH/PTHrP receptor are necessary for proper development of embryonic mammary gland in mice. Using a combination loss-of-function gain-of-function models, we now report PTHrP regulates series cell fate decisions central to survival morphogenesis epithelium formation nipple. is made epithelial cells bud and, during development, it interacts with surrounding mesenchymal induce dense...
Oncogenic osteomalacia (OO), a tumor-associated phosphate-wasting syndrome, provides an opportunity to identify regulators of renal phosphate homeostasis. We established cultures from OO-associated tumors. Conditioned medium these inhibited uptake in tubular epithelial cells. then compared RNA tumor-derived expressing inhibitory activity with which was not evident and identified candidate mRNAs specifically expressed by inhibiting transport. Testing candidates revealed that one protein,...
The cDNA-predicted amino acid sequence of parathyroid hormone-related protein (PTHrP) contains multiple basic motifs, suggesting that PTHrP undergoes extensive post-translational processing prior to secretion. secretory forms the peptide are currently unknown. To identify these forms, medium was harvested from three cell types: human renal carcinoma (SKRC-1) cells, keratinocytes, and rat insulinoma cells stably transfected with cDNA for PTHrP(1-141) (RIN-141 cells). Amino-terminal species...
Highlights•Enhanced mitochondrial GTP (mtGTP) production amplifies insulin secretion•mtGTP regulates PEPCK-M and cytosolic Ca2+, not OxPhos, to trigger secretion•Exuberant secretion enhanced biosynthesis can coexist without toxicity•mtGTP turnover enhances content, granule docking, massSummaryMechanisms coordinating pancreatic β cell metabolism with are essential for glucose homeostasis. One key mechanism of nutrient sensing uses the cycle. In this cycle, mtGTP synthesized by succinyl-CoA...
Knockout (KO) mouse models play critical roles in elucidating biological processes behind disease-associated or disease-resistant traits. As a presumed consequence of gene KO, mice display certain phenotypes. Based on insight into the molecular role said process, it is inferred that particular process causally underlies trait. This approach has been crucial towards understanding basis pathological and/or advantageous traits associated with Mertk KO mice. suffer from severe, early-onset...
Recent studies in transgenic mice have demonstrated that PTH-related protein (PTHrP), signaling through the type 1 PTH/PTHrP receptor (PTHR1), regulates endochondral bone development and epithelial-mesenchymal interactions during formation of mammary glands teeth. Recently, it has been shown loss-of-function mutations PTHR1 gene result a rare, lethal form dwarfism known as Blomstrand chondrodysplasia. These patients suffer from severe defects formation, but abnormalities breast tooth not...
PTH and PTH-related peptides (PTHrPs) interact with a common PTH/PTHrP receptor (type I), which is expressed in many tissues, including bone kidney. Amino-terminal PTHrPs also recognize receptors several nonclassical target some of these, the signaling mechanisms differ qualitatively from those classical type I receptor. In normal keratinocytes squamous carcinoma cell lines, PTHrP stimulate rise intracellular calcium, but not cAMP, suggesting existence an alternate, II SqCC/Y1 cells stably...
The PTHrP gene generates low-abundance mRNA and protein products that are not easily localized by in situ hybridization histochemistry or immunohistochemistry. We report here a PTHrP-lacZ knockin mouse which β-gal activity seems to provide simple sensitive read-out of expression. Introduction: PTH-related (PTHrP) is widely expressed fetal adult tissues, typically as maybe difficult localize conventional methods. created means surveying expression general identifying previously unrecognized...
Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) regulates insulin sensitivity by promoting hepatic clearance. Liver-specific inactivation or global null-mutation of Ceacam1 impairs extraction to cause chronic hyperinsulinemia, resulting in resistance and visceral obesity. In this study we investigated whether diet-induced implicates changes CEACAM1. We report that feeding C57/BL6J mice a high-fat diet reduced CEACAM1 levels &gt;50% beginning at 21 days, causing...