A5067579135- Diabetes Management and Research
- Pancreatic function and diabetes
- Diabetes and associated disorders
- Cancer-related Molecular Pathways
- Muscle Physiology and Disorders
- Ubiquitin and proteasome pathways
- Cardiomyopathy and Myosin Studies
- Sarcoma Diagnosis and Treatment
- Genetic Neurodegenerative Diseases
- Peptidase Inhibition and Analysis
- Cancer-related gene regulation
- Microtubule and mitosis dynamics
- Epigenetics and DNA Methylation
- Wnt/β-catenin signaling in development and cancer
- Diet and metabolism studies
- Metabolomics and Mass Spectrometry Studies
- NF-κB Signaling Pathways
- Metabolism and Genetic Disorders
- RNA and protein synthesis mechanisms
- Muscle metabolism and nutrition
- Cancer Genomics and Diagnostics
- Diabetes Treatment and Management
- Genetics, Aging, and Longevity in Model Organisms
- Ear and Head Tumors
- Cancer, Hypoxia, and Metabolism
Breakthrough
2024-2025
Breakthrough T1D
2018-2024
Springhouse
2023
KU Leuven
2022
Regeneron (United States)
2001-2017
New York University
1999-2004
Memorial Sloan Kettering Cancer Center
1994-2001
Columbia University Irving Medical Center
2000-2001
Molecular Oncology (United States)
2000
Spanish National Cancer Research Centre
2000
Skeletal muscle adapts to decreases in activity and load by undergoing atrophy. To identify candidate molecular mediators of atrophy, we performed transcript profiling. Although many genes were up-regulated a single rat model only small subset was universal all atrophy models. Two these encode ubiquitin ligases: Muscle RING Finger 1 ( MuRF1 ), gene designate Atrophy F-box MAFbx the latter being member SCF family E3 ligases. Overexpression myotubes produced whereas mice deficient either or...
Loss of myofibrillar proteins is a hallmark atrophying muscle. Expression muscle RING-finger 1 (MuRF1), ubiquitin ligase, markedly induced during atrophy, and MuRF1 deletion attenuates wasting. We generated mice expressing Ring-deletion mutant MuRF1, which binds but cannot ubiquitylate substrates. Mass spectrometry the bound in denervated identified many components. Upon denervation or fasting, muscles show loss myosin-binding protein C (MyBP-C) myosin light chains 2 (MyLC1 MyLC2) from...
Skeletal muscle size is regulated by anabolic (hypertrophic) and catabolic (atrophic) processes. We first characterized molecular markers of both hypertrophy atrophy identified a small subset genes that are inversely in these two settings (e.g. up-regulated an inducer hypertrophy, insulin-like growth factor-1 (IGF-1), down-regulated mediator atrophy, dexamethasone). The as being opposed to include the E3 ubiquitin ligase MAFbx (also known atrogin-1). next sought investigate mechanism which...
The F-box protein Skp2 (S-phase kinase-associated 2) positively regulates the G(1)-S transition by controlling stability of several G(1) regulators, such as cell cycle inhibitor p27. We show here that expression correlates directly with grade malignancy and inversely p27 levels in human lymphomas. To evaluate potential to deregulate growth vivo, we generated transgenic mice expressing targeted T-lymphoid lineage well double coexpressing activated N-Ras. A strong cooperative effect between...
Growth and differentiation factor 8 (GDF8) is a TGF-β superfamily member, negative regulator of skeletal muscle mass. GDF8 inhibition results in prominent growth mice, but less impressive hypertrophy primates, including man. Broad suggests another family member negatively regulates mass, its blockade enhances seen with GDF8-specific inhibition. Here we show that activin A the long-sought second regulator. Activin specific inhibition, on top leads to pronounced force production mice monkeys....
Loss of skeletal muscle mass and function in humans is associated with significant morbidity mortality. The role myostatin as a key negative regulator has supported the concept that inactivation could be useful approach for treating wasting diseases.We generated monoclonal blocking antibody (REGN1033) characterized its effects vitro using surface plasmon resonance biacore cell-based Smad2/3 signaling assays. REGN1033 was tested mice ability to induce hypertrophy prevent atrophy induced by...
Type 1 diabetes is a chronic autoimmune disease in which destruction of pancreatic β-cells causes life-threatening metabolic dysregulation. Numerous approaches are envisioned for new therapies, but limitations current clinical outcome measures significant disincentives to development efforts. C-peptide, direct byproduct proinsulin processing, quantitative biomarker β-cell function that not cleared by the liver and can be measured peripheral blood. Studies have established predictive...
Journal Article Prognostic Implications of p53 Nuclear Overexpression and High Proliferation Index Ki-67 in Adult Soft-Tissue Sarcomas Get access Marija Drobnjak, Drobnjak Search for other works by this author on: Oxford Academic PubMed Google Scholar Esther Latres, Latres Daphna Pollack, Pollack Martin Karpeh, Karpeh Maria Dudas, Dudas James M. Woodruff, Woodruff Murray F. Brennan, Brennan Carlos Cordon-Cardo JNCI: the National Cancer Institute, Volume 86, Issue 7, 6 April 1994, Pages...
Conditional mutagenesis is becoming a method of choice for studying gene function, but constructing conditional alleles often laborious, limited by target structure, and at times, prone to incomplete ablation. To address these issues, we developed technology termed conditionals inversion (COIN). Before activation, COINs contain an inverted module (COIN module) that lies inertly within the antisense strand resident gene. When into sense site-specific recombinase, COIN causes termination...
Male mice lacking both the Ink4c and Ink4d genes, which encode two inhibitors of D-type cyclin-dependent kinases (Cdks), are infertile, whereas female fecundity is unaffected. Both p18(Ink4c) p19(Ink4d) expressed in seminiferous tubules postnatal wild-type mice, being largely confined to postmitotic spermatocytes undergoing meiosis. Their combined loss associated with delayed exit spermatogonia from mitotic cell cycle, leading retarded appearance meiotic cells that do not properly...
Trb3, a mammalian homolog of Drosophila tribbles, was proposed as suppressor Akt activity, predominantly in conditions fasting and diabetes. Given these prior studies, we sought to determine whether Trb3 plays major role modulating hepatic insulin sensitivity. To answer this question, produced mice which lacZ reporter knocked into the locus containing gene Trib3, resulting Trib3 null animal. expression analyses demonstrated that is expressed liver, adipose tissues, heart, kidney, lung, skin,...
The F-box protein betaTrcp1 controls the stability of several crucial regulators proliferation and apoptosis, including certain inhibitors NF-kappaB family transcription factors. Here we show that mammary glands betaTrcp1(-/-) female mice display a hypoplastic phenotype, whereas no effects on cell are observed in other somatic cells. To investigate further role gland development, generated transgenic expressing human targeted to epithelial cells under control mouse tumor virus (MMTV) long...
Activation of Jun N-kinase (JNK) and NF-κB transcription factor are the hallmarks cellular response to stress. Phosphorylation inhibitor (IκB) by respective stress-inducible kinases (IKK) is a key event in activation. β-TrCP F-box protein mediates ubiquitination phosphorylated IκB via recruitment SCF<sup>β-TrCP</sup>-Roc1 E3 ubiquitin ligase complex. Subsequent proteasome-dependent degradation results activation pathway. We found that variety stress stimuli induce an increase steady state...