A5068963912- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Cancer, Hypoxia, and Metabolism
- Mitochondrial Function and Pathology
- RNA Research and Splicing
- Erythrocyte Function and Pathophysiology
- Epigenetics and DNA Methylation
- Amino Acid Enzymes and Metabolism
- Sulfur Compounds in Biology
- Histone Deacetylase Inhibitors Research
- Metabolism and Genetic Disorders
- Pharmacogenetics and Drug Metabolism
- Cancer, Lipids, and Metabolism
- Metal-Catalyzed Oxygenation Mechanisms
- Crystallization and Solubility Studies
- Immune cells in cancer
- Endoplasmic Reticulum Stress and Disease
- Sesquiterpenes and Asteraceae Studies
- Microbial Natural Products and Biosynthesis
- Enzyme Catalysis and Immobilization
- Ion channel regulation and function
- Synthetic Organic Chemistry Methods
- Metabolomics and Mass Spectrometry Studies
- X-ray Diffraction in Crystallography
- Lipid Membrane Structure and Behavior
Rockefeller University
2019-2025
University of Rochester
2016-2021
University of Michigan
2014
Mitochondria must maintain adequate amounts of metabolites for protective and biosynthetic functions. However, how mitochondria sense the abundance regulate metabolic homeostasis is not well understood. In this work, we focused on glutathione (GSH), a critical redox metabolite in mitochondria, identified feedback mechanism that controls its through mitochondrial GSH transporter, SLC25A39. Under physiological conditions, SLC25A39 rapidly degraded by protease AFG3L2. Depletion dissociates...
Abstract Epitranscriptomic mechanisms linking tRNA function and the brain proteome to cognition complex behaviors are not well described. Here, we report bi-directional changes in depression-related after genetic disruption of neuronal cytosine methylation, including conditional ablation transgene-derived overexpression Nsun2 mouse prefrontal cortex (PFC). Neuronal Nsun2-deficiency was associated with a decrease m 5 C levels, resulting deficits expression 70% Gly isodecoders. Altogether,...
Abstract Insect societies are tightly integrated, complex biological systems in which group-level properties arise from the interactions between individuals 1–4 . However, these have not been studied systematically and therefore remain incompletely known. Here, using a reverse engineering approach, we reveal that unlike solitary insects, ant pupae extrude secretion derived moulting fluid is rich nutrients, hormones neuroactive substances. This elicits parental care behaviour rapidly removed...
Utilization of specific codons varies between organisms. Cancer represents a model for understanding DNA sequence evolution and could reveal causal factors underlying codon evolution. We found that across human cancer, arginine are frequently mutated to other codons. Moreover, limitation—a feature tumor microenvironments—is sufficient induce codon–switching mutations in colon cancer cells. Such switching events encode mutant proteins with residue substitutions. Mechanistically, limitation...
Mechanosensitive ion channels mediate transmembrane currents activated by mechanical forces. A mechanosensitive channel called TACAN was recently reported. We began to study with the intent understand how it senses forces and functions as an channel. Using cellular patch-recording methods, we failed identify activity. membrane reconstitution found that TACAN, at high protein concentrations, produces heterogeneous conduction levels are not most consistent disruptions of lipid bilayer....
Suicide is a major public health concern, and the number of deaths by suicide has been increasing in recent years US. There are various biological risk factors for suicide, but causal molecular mechanisms remain unknown, suggesting that investigation novel integrative approaches necessary. Transfer (t)RNAs their modifications, including cytosine methylation (m5C), have received little attention regarding role normal or diseased brain function, though they dynamic mediators protein synthesis....
The plant-derived sesquiterpene lactone micheliolide was recently found to possess promising antileukemic activity, including the ability target and kill leukemia stem cells. Efforts toward improving biological activity of investigating its mechanism action have been hindered by paucity preexisting functional groups amenable for late-stage derivatization this molecule. Here, we report implementation a probe-based P450 fingerprinting strategy rapidly evolve engineered catalysts useful regio-...
Glutathione (GSH) is a highly abundant tripeptide thiol that performs diverse protective and biosynthetic functions in cells. While changes GSH availability are associated with inborn errors of metabolism, cancer neurodegenerative disorders, studying the limiting role physiology disease has been challenging due to its tight regulation. To address this, we generated cell mouse models express bifunctional glutathione-synthesizing enzyme from Streptococcus thermophilus (GshF), which possesses...
The main thickening agent or soap in multipurpose grease, lithium 12-hydroxystearate, is a chemical commodity for the auto industry. This compound obtained from castor oil via series of transformations. first step, hydrogenation oil, has been developed into laboratory experiment second-year undergraduate organic chemistry. Students are introduced to catalytic transfer (CTH) as method reduce carbon–carbon double bond ricinoleic acid, fatty acid oil. perform comparative analysis based on...
Significance Heterozygous in-frame mutations in human STAT3 coding regions underlie the only known autosomal dominant form of hyper IgE syndrome (AD HIES). About 5% familial cases remain unexplained. We report a deep intronic heterozygous mutation, c.1282-89C>T, 7 relatives with AD HIES. This mutation creates new exon, encoding mRNA (D427ins17) and mutant loss-of-function, dominant-negative protein. protein was not detected cells from patient. show that D427ins17 allele is despite...
The multidomain, catalytically self-sufficient cytochrome P450 BM-3 from Bacillus megaterium (P450
Alkb homolog 7 (ALKBH7) is a mitochondrial α-ketoglutarate dioxygenase required for DNA alkylation-induced necrosis, but its function and substrates remain unclear. Herein, we show ALKBH7 regulates dialdehyde metabolism, which impacts the cardiac response to ischemia-reperfusion (IR) injury. Using multi-omics approach, find no evidence functions as prolyl-hydroxylase, do Alkbh7-/- mice have elevated glyoxalase I (GLO-1), detoxifying enzyme. Metabolic pathways related glycolytic by-product...
Heme-containing proteins have recently attracted increasing attention for their ability to promote synthetically valuable transformations not found in nature. Following the recent discovery that engineered variants of myoglobin can catalyze direct conversion organic azides aldehydes, we investigated azide oxidative deamination reactivity a variety hemoproteins featuring different heme coordination environments. Our studies show although several heme-containing enzymes possess basal activity...
Fibrolamellar hepatocellular carcinoma (FLC) is a usually lethal primary liver cancer driven by somatic dysregulation of protein kinase A. We show that the proteome FLC tumors distinct from adjacent nontransformed tissue. These changes can account for some cell biological and pathological alterations in cells, including their drug sensitivity glycolysis. Hyperammonemic encephalopathy recurrent problem these patients, established treatments based on assumption failure are unsuccessful. many...