A5084288633- Nuclear Structure and Function
- RNA Research and Splicing
- Congenital heart defects research
- Cardiomyopathy and Myosin Studies
- Muscle Physiology and Disorders
- Growth Hormone and Insulin-like Growth Factors
- RNA modifications and cancer
- Hypothalamic control of reproductive hormones
- Cancer-related molecular mechanisms research
- Virus-based gene therapy research
- Estrogen and related hormone effects
- Pluripotent Stem Cells Research
- Hippo pathway signaling and YAP/TAZ
- Cardiovascular Effects of Exercise
- Cardiac Fibrosis and Remodeling
- Genomics and Chromatin Dynamics
- Tissue Engineering and Regenerative Medicine
- Ion channel regulation and function
- CRISPR and Genetic Engineering
- Mitochondrial Function and Pathology
- Adipose Tissue and Metabolism
- Cardiac electrophysiology and arrhythmias
- Angiogenesis and VEGF in Cancer
- Cancer-related Molecular Pathways
- RNA Interference and Gene Delivery
Qatar University
2021-2024
University of Ottawa
2007-2018
Harvard University
2001-2015
National Cancer Institute
2006
Boston Children's Museum
2006
New York University
2006
Brigham and Women's Hospital
2003-2005
Howard Hughes Medical Institute
2003-2005
University of Vermont
2004
Johns Hopkins University
2004
Mutations in the gamma2 subunit (PRKAG2) of AMP-activated protein kinase produce an unusual human cardiomyopathy characterized by ventricular hypertrophy and electrophysiological abnormalities: Wolff-Parkinson-White syndrome (WPW) progressive degenerative conduction system disease. Pathological examinations affected hearts reveal vacuoles containing amylopectin, a glycogen-related substance.To elucidate mechanism which PRKAG2 mutations with abnormalities, we constructed transgenic mice...
Despite advances in the molecular biology of cardiac myosin binding protein-C (cMyBP-C), little is understood about its precise role muscle contraction, particularly intact heart. We tested hypothesis that cMyBP-C central to time course and magnitude left ventricular systolic elastance (chamber stiffening), assessed mechanisms for this influence hearts, trabeculae, skinned fibers from wild-type (+/+) homozygous truncated (t/t) male mice. protein was not detected by gel electrophoresis or...
Heterotrimeric G proteins are involved in the transduction of hormonal and sensory signals across plasma membranes eukaryotic cells. Hence, they a critical point control for variety agents that modulate cellular function. Activation these is dependent on GTP binding to their alpha (Galpha) subunits. Regulators protein signaling (RGS) bind specifically activated Galpha proteins, potentiating intrinsic GTPase activity thus expediting termination signaling. Although there several points most...
Twenty hFSH isoforms were isolated from human pituitary extracts, 15 of which highly pure. The mild purification procedure, used a FSH RRA to monitor activity, involved an initial fractionation extracts by gel filtration and isoelectric focusing. Six pI regions (mean values, 3.63, 3.88, 4.07, 4.23, 4.84, 5.13) (h) obtained further fractionated on ion exchange HPLC. Recoveries radioreceptor activity at each stage greater than 80%. Fifteen isoform preparations judged as near homogeneous...
We sought to identify an essential component of the TEAD4/VGLL4 transcription factor complex that controls vascular endothelial growth A (VEGFA) expression in muscle. yeast 2-hybrid screen was used clone a novel TEAD4 from human heart cDNA library. identified interferon response 2 binding protein (IRF2BP2) and confirmed its presence vivo by coimmunoprecipitation mammalian assays. Coexpression IRF2BP2 with or TEAD1 alone potently activated, whereas knockdown reduced, VEGFA C(2)C(12) muscle...
Significance We demonstrate that hearts lacking the sarcomere protein cardiac myosin binding C (MYBPC) undergo altered development due to an extra round of postnatal cell division. Normal myocytes replicate rapidly during fetal life, a final division shortly after birth, cease dividing, and increase in size prepubescent life. MYBPC has unexpected function—inhibition myocyte cytokinesis. MYBPC-deficient additional cytokinesis, resulting increased numbers greater proportion mononuclear...
The post-natal heart adapts to stress and overload through hypertrophic growth, a process that may be pathologic or beneficial (physiologic hypertrophy). Physiologic hypertrophy improves cardiac performance in both healthy diseased individuals, yet the mechanisms propagate this favorable adaptation remain poorly defined. We identify cytokine cardiotrophin 1 (CT1) as factor capable of recapitulating key features physiologic growth including transient reversible myocardium, stimulation...
Previous studies have shown that highly purified isoforms of human pituitary LH exhibited a 20-fold range in vitro bioactivities. The aim this study was to determine the corresponding plasma half-lives, metabolic clearance rates (MCR), and vivo bioactivities these (h) isoforms. Cannulated adult male rats were administered hLH as bolus i.v. injection. For half-life studies, blood then serially collected over 6-h period, serum assayed for using specific immunofluorometric assay. All (n = 19)...
We examined the effect of cardiac myosin binding protein-C (cMyBP-C) on contractile efficiency in isovolumically contracting left ventricle (LV) and internal viscosity oscillatory work production skinned myocardial strips. A 6-week diet 0.15% 6- n -propyl-2-thiouracil (PTU) was fed to wild-type (+/+ PTU ) homozygous-truncated cMyBP-C (t/t mice starting at age ≈8 weeks leading a heavy chain (MHC) isoform profile 10% α-MHC 90% β-MHC both groups. Western blot analysis confirmed that present +/+...
Mutations in the A-type lamin (LMNA) gene are associated with age-associated degenerative disorders of mesenchymal tissues, such as dilated cardiomyopathy, Emery-Dreifuss muscular dystrophy, and limb-girdle dystrophy. The molecular mechanisms that connect mutations LMNA different human diseases poorly understood. Here, we report identification a Muscle-enriched Lamin-interacting Protein, MLIP (C6orf142 2310046A06rik), unique single copy is an innovation amniotes (reptiles, birds, mammals)....
Abstract Striated muscle needs to maintain cellular homeostasis in adaptation increases physiological and metabolic demands. Failure do so can result rhabdomyolysis. The identification of novel genetic conditions associated with rhabdomyolysis helps shed light on hitherto unrecognized homeostatic mechanisms. Here we report seven individuals six families from different ethnic backgrounds biallelic variants MLIP, which encodes the muscular lamin A/C-interacting protein, MLIP. Patients...
Haploinsufficiency of T-box transcription factor 5 (TBX5) causes human Holt-Oram syndrome (HOS), a developmental disorder characterized by skeletal and heart malformations. Mice carrying Tbx5 null allele (Tbx5(+/Delta)) have malformations in digits, wrists, sternum joints, regions where is expressed. We demonstrate that mice deficient connexin 40 (Cx40), Tbx5-regulated gap junction component, shared axial appendicular with Tbx5(+/Delta) mice. Although no role skeleton patterning has been...
AbstractThe E2F transcription factors are key downstream targets of the retinoblastoma protein tumor suppressor. They known to regulate expression genes that control fundamental biological processes including cellular proliferation, apoptosis and differentiation. However, considerable questions remain about precise roles individual family members. This study shows E2F3 is essential for normal cardiac development. E2F3-loss impairs proliferative capacity embryonic myocardium most E2f3-/- mice...
Exercise training is beneficial for preserving cardiac function postmyocardial infarction (post-MI), but the underlying mechanisms are not well understood. We investigated one possible mechanism, brain-derived neurotrophic factor (BDNF)-tropomyosin-related kinase B (TrkB) signaling, with TrkB blocker ANA-12 (0.5 mg·kg-1·day-1). Male Wistar rats underwent sham surgery or ligation of left descending coronary artery. The surviving MI were allocated as follows: sedentary treated vehicle,...
ABSTRACT In a recent study, five- to eightfold range in human FSH radioreceptor activity (RRA) was documented for highly purified isoforms of when the data were expressed on an protein content basis as determined by amino acid analysis. This study examined vitro bioactivity and immunoactivity these preparations. biological showed with high correlation RRA values ( r =0·82). A similar obtained specific radioimmunoassay two-site immunoassay correlations again observed between each other,...
ABSTRACT Thirty-nine human LH (hLH) isoforms were chromatographically separated from pituitary extracts using a mild purification procedure which consisted of preparative isoelectric focusing, high-performance ion-exchange chromatography and immobilized metal-affinity chromatography. Twenty these hLH characterized by radioreceptor assay, SDS-PAGE amino acid analysis, 17 shown to be highly purified (>90% pure). The specific activities ranged 1980 38 650 IU/mg protein in terms the 2nd IS...
Muscle-enriched A-type lamin-interacting protein (Mlip) is a recently discovered Amniota gene that encodes proteins of unknown biological function. Here we report Mlip’s direct interaction with chromatin, and it may function as transcriptional co-factor. Chromatin immunoprecipitations microarray analysis demonstrated propensity for Mlip to associate genomic regions in close proximity genes control tissue-specific differentiation. Gel mobility shift assays confirmed complexes DNA. Blocking...
Muscle-enriched A-type lamin-interacting protein (MLIP) is an emerging involved in cellular homeostasis and stress adaptation. Eukaryotic cells regulate various processes, including metabolism, DNA repair, cell cycle progression, to maintain homeostasis. Disruptions this can lead diseases such as cancer, characterized by uncontrolled growth division. This review aims explore for the first time unique role MLIP may play cancer development given its interactions with PI3K/Akt/mTOR pathway,...
The mammalian myocardium grows rapidly during early development due to cardiomyocyte proliferation, which later transitions cell hypertrophy sustain the heart’s postnatal growth. Although this transition in heart is consistently preserved biology, little known about regulatory mechanisms that link proliferation suppression with induction. We reasoned production of a micro-RNA(s) could serve as key bridge permit changes gene expression control changed fate cardiomyocytes. used sequential...