- Cancer, Hypoxia, and Metabolism
- Ion channel regulation and function
- Metabolism, Diabetes, and Cancer
- RNA modifications and cancer
- Cardiac electrophysiology and arrhythmias
- Neuroscience and Neuropharmacology Research
- Sirtuins and Resveratrol in Medicine
- Extracellular vesicles in disease
- RNA Interference and Gene Delivery
- Virus-based gene therapy research
- COVID-19 Clinical Research Studies
- Clinical Nutrition and Gastroenterology
- Tissue Engineering and Regenerative Medicine
- Retinal Development and Disorders
- Neuroscience and Neural Engineering
- Neurogenesis and neuroplasticity mechanisms
- Genetics, Aging, and Longevity in Model Organisms
- Diet and metabolism studies
- Transgenic Plants and Applications
- CRISPR and Genetic Engineering
- Nerve injury and regeneration
- Language Development and Disorders
- Biological Research and Disease Studies
- Animal Genetics and Reproduction
- Blood properties and coagulation
Cornell University
2004-2024
California State University, Dominguez Hills
2022
Laboratory of Molecular Genetics
2016
Ithaca College
2006
Glutamine is an essential nutrient for cancer cell proliferation, especially in the context of citric acid cycle anaplerosis. In this manuscript we present results that collectively demonstrate that, three major mammalian glutaminases identified to date, lesser studied splice variant gene gls , known as Glutaminase C (GAC), important tumor metabolism. We show although levels both kidney-type isoforms are elevated vs. normal tissues, GAC distinctly mitochondrial. also most responsive...
Directed differentiation of embryonic stem cells indicates that mesodermal lineages in the mammalian heart (cardiac, endothelial, and smooth muscle cells) develop from a common, multipotent cardiovascular precursor. To isolate characterize lineage potential resident pool progenitor (CPcs), we developed BAC transgenic mice which enhanced green fluorescent protein (EGFP) is placed under control c-kit locus (c-kit -EGFP mice). Discrete c-kit-EGFP + were observed at different stages hearts,...
The peripheral nervous system has complex and intricate ramifications throughout many target organ systems. To date this not been effectively labeled by genetic markers, due largely to inadequate transcriptional specification minimum promoter constructs. Here we describe transgenic mice in which enhanced green fluorescent protein (eGFP) is expressed under the control of endogenous choline acetyltransferase (ChAT) regulatory elements, knock-in eGFP within a bacterial artificial chromosome...
Abstract Many transformed cells exhibit altered glucose metabolism and increased utilization of glutamine for anabolic bioenergetic processes. These metabolic adaptations, which accompany tumorigenesis, are driven by oncogenic signals. Here we report that the transcription factor c-Jun, product proto-oncogene JUN , is a key regulator mitochondrial glutaminase (GLS) levels. Activation c-Jun downstream Rho GTPase signalling leads to elevated GLS gene expression activity. In human breast cancer...
The mitochondrial enzyme glutaminase (GLS) is frequently up-regulated during tumorigenesis and being evaluated as a target for cancer therapy. GLS catalyzes the hydrolysis of glutamine to glutamate, which then supplies diverse metabolic pathways with carbon and/or nitrogen. Here, we report that SIRT5, NAD+-dependent lysine deacylase, plays key role in stabilizing GLS. In transformed cells, SIRT5 regulates metabolism by desuccinylating thereby protecting it from ubiquitin-mediated...
Efforts to target glutamine metabolism for cancer therapy have focused on the glutaminase isozyme GLS. The importance of other isozyme, GLS2, in has remained unclear, and it been described as a tumor suppressor some contexts. Here, we report that GLS2 is upregulated essential luminal-subtype breast tumors, which account >70% incidence. We show expression elevated by GATA3 cells but suppressed promoter methylation basal-subtype cells. Although luminal cancers resist GLS-selective inhibitors,...
Extracellular vesicles (EVs), including exosomes and microvesicles (MVs), have emerged as a major form of intercellular communication, playing important roles in several physiological processes diseases, cancer. EVs generated by cancer cells contain variety proteins RNA species that can be transferred between well non-transformed (normal) cells, thereby impacting number aspects progression. Here we show how oncogenic transformation influences the biogenesis function using mouse embryonic...
Abstract Tumour‐derived microvesicles (MVs) serve as critical mediators of cell‐to‐cell communication in the tumour microenvironment. So far, underlying mechanisms MV biogenesis, especially how key tumorigenesis signals such abnormal EGF signalling regulates release, remain unclear. Here, we set out to establish reliable readouts for biogenesis and then explore molecular that regulate generation. We found Rho family small G protein Cdc42 is a convergent node multiple regulatory occur...
Calcium release through ryanodine receptors (RYR) activates calcium-dependent membrane conductances and plays an important role in excitation-contraction coupling smooth muscle. The specific RYR isoforms associated with this muscle, the of RYR-associated proteins such as FK506 binding (FKBPs), has not been clearly established, however. FKBP12.6 interact RYR2 Ca2+ channels absence these predictably alters amplitude kinetics unitary events (Ca2+ sparks). To evaluate FBKP12.6 processes we...
The metabolic microenvironment of tumors is characterized by fluctuating and limited nutrient availability. To survive these conditions, cancer cell-intrinsic mechanisms sense signal nutritional status. We describe how glutaminase (GLS) destabilized lysine succinylation stabilized the NAD+-dependent desuccinylase sirtuin 5 (SIRT5), coupling levels to flux.
Conditional inactivation of individual genes in mice using site-specific recombinases is an extremely powerful method for determining the complex roles mammalian developmental and tissue-specific contexts, a major goal post-genomic research. However, process generating with recombinase recognition sequences placed at specific locations within gene, while maintaining functional allele, time consuming, expensive technically challenging. We describe system that combines gene trap DNA inversion...
Ca + -activated Cl − channel (CLCA) proteins are encoded by a family of highly related and clustered genes in mammals that markedly upregulated inflammation have been shown to affect chloride transport. Here we describe the cellular processing regulatory sequences underlying murine (m) CLCA4 proteins. The 125-kDa mCLCA4 gene product is cleaved 90- 40-kDa fragments, NH 2 - COOH-terminal fragments secreted, where they found cell media associated with plasma membrane. full-length protein only...
Abstract Developing therapeutic strategies against COVID-19 has gained widespread interest given the likelihood that new viral variants will continue to emerge. Here we describe one potential strategy which involves targeting members of glutaminase family mitochondrial metabolic enzymes (GLS and GLS2), catalyze first step in glutamine metabolism, hydrolysis glutamate. We show three examples where GLS expression increases during coronavirus infection host cells, another GLS2 is upregulated....
Dual language development and disorders: A handbook on bilingualism second learning, 3rd edition J. Paradis, F. Genesee & M. B. Crago (2021) Baltimore, MD: Brookes Publishing Language disorders in bilingual children adults, K. Kohnert, D. Ebert T. Pham San Diego, CA: Plural