A5028733853- Mitochondrial Function and Pathology
- Sirtuins and Resveratrol in Medicine
- RNA modifications and cancer
- Adipose Tissue and Metabolism
- Synthesis and biological activity
- Calcium signaling and nucleotide metabolism
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Autophagy in Disease and Therapy
- ATP Synthase and ATPases Research
- Tumors and Oncological Cases
- Biochemical and Molecular Research
- Neuroinflammation and Neurodegeneration Mechanisms
- RNA Interference and Gene Delivery
- Metabolism and Genetic Disorders
- Endoplasmic Reticulum Stress and Disease
- Tuberous Sclerosis Complex Research
- Lipid metabolism and disorders
- Microbial Natural Products and Biosynthesis
- Tryptophan and brain disorders
- PI3K/AKT/mTOR signaling in cancer
- Synthesis and Characterization of Pyrroles
- DNA and Nucleic Acid Chemistry
- Bioactive Compounds and Antitumor Agents
- Histiocytic Disorders and Treatments
Hope College
2009-2023
Van Andel Institute
2017
University of Wisconsin–Madison
2010-2015
Molecular Research Institute
2013
University of Isfahan
2008
Mitochondria play a central role in oxidative energy metabolism and age-related diseases such as cancer. Accumulation of spurious damage can cause cellular dysfunction. Antioxidant pathways that rely on NADPH are needed for the reduction glutathione maintenance proper redox status. The mitochondrial matrix protein isocitrate dehydrogenase 2 (IDH2) is major source NADPH. Previously, we demonstrated NAD(+)-dependent deacetylase SIRT3 was essential prevention hearing loss mice fed calorically...
Abstract Tuberous sclerosis complex (TSC) is a rare genetic disease causing multisystem growth of benign tumours and other hamartomatous lesions, which leads to diverse debilitating clinical symptoms. Patients are born with TSC1 or TSC2 mutations, somatic inactivation wild-type alleles drives MTOR activation; however, second hits TSC1/TSC2 not always observed. Here, we present the genomic landscape TSC hamartomas. We determine that lesions contain low mutational burden relative carcinomas,...
Acylation of lysine is an important protein modification regulating diverse biological processes. It was recently demonstrated that members the human Sirtuin family are capable catalyzing long chain deacylation, in addition to well-known NAD(+)-dependent deacetylation activity [Feldman, J. L., Baeza, J., and Denu, M. (2013) Biol. Chem. 288, 31350-31356]. Here we provide a detailed kinetic structural analysis describes interdependence NAD(+)-binding acyl-group selectivity for series Sirtuins,...
Lysine acetylation is rapidly becoming established as a key post-translational modification for regulating mitochondrial metabolism. Nonetheless, distinguishing regulatory sites from among the thousands identified by mass spectrometry and elucidating how these modifications alter enzyme function remain primary challenges. Here, we performed multiplexed quantitative to measure changes in mouse liver acetylproteome response acute chronic alterations nutritional status, integrated data sets...
Twenty-one α,β-unsaturated ketone analogs of combretastatin-A4 (CA-4) that were designed for good solubility in aqueous media synthesized. Compounds defined as Type A derived from phenylacetone, which subclass I contained ortho-, meta- or no substituents, sub-class II para-substituents, and III consisted two substituents. B compounds cyclopropyl 2-fluorobenzyl ketone. The cis-configuration the target was ascertained through a single crystal X-ray crystallographic analysis fluorine-containing...
Abstract Mitochondria play a central role in energy production and cellular metabolism. contain their own small genome (mitochondrial DNA, mtDNA) that carries the genetic instructions for proteins required ATP synthesis. The mitochondrial proteome, including transcriptional machinery, is subject to post‐translational modifications (PTMs), acetylation phosphorylation. We set out determine whether PTMs of associated with mtDNA may provide potential mechanism regulation gene expression. Here,...
Hairpin polyamide analogs of distamycin A (1) were designed and synthesized to evaluate their ability bind 5′-ATAGA-3′ 5′-AGATA-3′ sequences which are important elements for controlling the function Brn-3b GATA-3 transcriptional factors, respectively. The hairpin polyamides composed pyrrole imidazole units linked together via a γ-aminobutyrate (GABA) unit. Hairpins 2b (Py-Py-Im-γ-Py-Py-Py) 2c (Im-Py-Py-γ-Py-Py-Py) target respective cognate sequences. Preliminary biophysical studies including...
The synthesis of a series 2-(3-arylacryloyl)-3-methylquinoxaline 1,4dioxides is reported.In-vitro cytotoxic activity these compounds was evaluated via the MTT assay in B16 murine melanoma and L1210 leukemia cell lines.A dichloro analogue found to be most > 30-fold more active than quinoxaline control (IC50 = 2 vs. 67 μΜ LI210, respectively).These results suggest that containing two bioactive moieties could developed as hypoxic selective cytotoxins.Vol.14, No. 5, 2008...
Abstract Review: about 70 refs.
The mitochondrial proteome is subject to abundant post-translational modifications, including lysine acetylation and phosphorylation of serine, threonine, tyrosine. biological function the majority these protein modifications unknown. Proteins required for transcription translation DNA (mtDNA) are modification. This suggests that reversible may serve as a regulatory mechanism gene transcription, akin mechanisms controlling nuclear expression. We set out determine whether or controls RNA...
Complexation of TT9C3, TT12C4 and HT18C6 as n-donor, with IBr σ-acceptor has been studied at different temperatures in carbon tetrachloride solution.Macrocycle + « * Macrocycle.IBr
Mitochondria are the metabolic centers of cell and critical players in initiating programmed death. Mitochondrial dysfunction dysregulated apoptosis contribute to a number disease states, including inherited mitochondrial syndromes, neurological disorders, cancer. Critical both function is architecture membranes. A mitochondrion comprised an inner outer membrane composed numerous phospholipids, cardiolipin, phospholipid found exclusively mitochondria. Cardiolipin binds cytochrome c membrane,...
Mitochondrial DNA (mtDNA) encodes 13 of the protein subunits oxidative phosphorylation pathway, pathway that produces majority ATP in eukaryotic cells. dysfunction is associated with neurodegenerative disorders, cancer, inherited mitochondrial diseases, and other pathologies, making biochemistry an important area investigation. However, there lacks understanding key elements this biochemistry, including mechanisms regulate mtDNA transcription. known to be complexed various proteins...
Mitochondrial DNA (mtDNA) encodes for 13 protein components required oxidative phosphorylation (OXPHOS), the primary cellular energy production pathway. While critical roles of mitochondria in metabolism and function are well established, mechanisms regulating expression mtDNA‐encoded genes poorly understood. Defects regulation mtDNA transcription implicated numerous pathologies such as neurodegenerative disorders cancers. is complexed to proteins structures known nucleoids, which some play...
Mammalian cells contain genetic information in two compartments, the nucleus and mitochondria. Mitochondrial DNA (mtDNA) encodes thirteen protein subunits required for oxidative phosphorylation. The remaining mitochondrial proteome, including additional phosphorylation subunits, proteins necessary mtDNA replication, expression, stability, is encoded by nuclear genome. Therefore, to respond metabolic changes, gene expression must be coordinated with expression. While control of widely...
Mammalian cells contain genetic information in two compartments, the nucleus and mitochondria. Mitochondrial DNA (mtDNA) encodes thirteen protein subunits required for oxidative phosphorylation. The remaining mitochondrial proteome is encoded by nuclear genome; which includes additional phosphorylation subunits, as well proteins necessary mtDNA replication, expression stability. Therefore, to respond metabolic changes, gene must be coordinated with expression. While control of widely...