A5068509621- Neuroscience and Neuropharmacology Research
- Molecular Sensors and Ion Detection
- Ion channel regulation and function
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Lipid Membrane Structure and Behavior
- RNA modifications and cancer
- Chemical Synthesis and Analysis
- Cancer-related molecular mechanisms research
- Receptor Mechanisms and Signaling
- Neuroscience and Neural Engineering
- Genetics, Bioinformatics, and Biomedical Research
- Cardiac electrophysiology and arrhythmias
- Photoreceptor and optogenetics research
- Advanced NMR Techniques and Applications
- Enzyme Structure and Function
- Nicotinic Acetylcholine Receptors Study
- Cardiac Ischemia and Reperfusion
- Protein Structure and Dynamics
- Electron Spin Resonance Studies
- Mass Spectrometry Techniques and Applications
- Nitric Oxide and Endothelin Effects
- Plant Disease Resistance and Genetics
- Hybrid Renewable Energy Systems
- Crystallography and molecular interactions
Saint Joseph's University
2024
University of the Sciences
2018-2022
Division of Chemistry
2018-2019
Carnegie Mellon University
2008-2017
Rush University Medical Center
2012-2013
University of Pittsburgh
2005-2006
Metastasis-associated lung adenocarcinoma transcript 1 ( Malat1/ MALAT1, mouse/human), a highly conserved long noncoding (lnc) RNA, has been linked with several physiological processes, including the alternative splicing, nuclear organization, and epigenetic modulation of gene expression. MALAT1 also implicated in metastasis tumor proliferation multiple cancer types. The 3' terminal stability element for expression (ENE) assumes triple-helical configuration that promotes its accumulation...
We describe a scheme for tagging an alanine-based peptide with Cu(II) and nitroxide to measure unfolding transitions. The enhancement in longitudinal relaxation rate of the due presence was measured at physiological temperatures by pulsed electron spin resonance (ESR). change provided average interspin distance between nitroxide. Control experiments on proline-based verify robustness method. distances temperature is accord helicity circular dichroism. data provide opportunity examine process...
N-methyl-d-aspartate receptors (NMDARs) are members of the ionotropic glutamate receptor family that mediate excitatory synaptic transmission in central nervous system. The channels NMDARs permeable to Ca2+ but blocked by Mg2+, distinctive properties underlie essential brain processes such as induction plasticity. However, due limited structural information about NMDAR transmembrane ion channel forming domain, mechanism divalent cation permeation and block is understood poorly. In this paper...
The ionotropic glutamate receptors are localized in the pre- and postsynaptic membrane of neurons brain. Activation by principal excitatory neurotransmitter allows ligand binding domain to change conformation, communicating opening channel for ion conduction. free energy GluR2 S1S2 (S1S2) closure transition was computed using a combination thermodynamic integration umbrella sampling modeling methods. A path that involves lowering charge on E705 chosen clarify role this site residue....
Ion selectivity-filter structures are strikingly similar throughout the large family of K+ channels and other p-loop-like receptors (i.e., glutamate receptors). At same time, triggers for opening these channels, or gating, diverse. Two questions that remain unanswered regarding are: 1) what force(s) stabilize closed non-conducting channel-pore conformation? And 2) is free energy associated with transitioning from a (non-conducting) to an open (conducting) The effects charge hydrophobicity on...
The glycine receptor (GlyR), a member of the pentameric ligand-gated ion channel superfamily, is major inhibitory neurotransmitter-gated in spinal cord and brainstem. In these receptors, extracellular domain binds agonists, antagonists various other modulatory ligands that act allosterically to modulate function. structures homologous receptors binding proteins provide templates for modeling ligand-binding GlyR, but limitations sequence homology structure resolution impact on studies....
The 3' end of the ∼7 kb lncRNA MALAT1 contains an evolutionarily and structurally conserved element for nuclear expression (ENE) which confers protection from cellular degradation pathways. Formation ENE triple helix is required to support transcript accumulation, leading persistent oncogenic activity in multiple cancer types. Though specific mechanism triplex-mediated remains unknown, triplex has been identified as a promising target therapeutic intervention. Interestingly, maturation step...
The accumulation of the 8-kb oncogenic long noncoding MALAT1 RNA in cells is dependent on presence a protective triple helix structure at 3' terminus. While recent studies have examined functional importance numerous base triples within triplex and its immediately adjacent pairs, peripheral duplex elements has not been thoroughly investigated. To investigate linker region that was previously described as unstructured, we employed variety assays including thermal melting, protection from...
Major advances have been made on the inhibition gate and ATP site of K(ir)6.2 subunit K(ATP) channel, but little is known about conformational coupling between two. mutations dramatically disrupt ATP-dependent gating without effect ligand-independent gating, observed as interconversions active burst inactive interburst conformations in absence ATP. This suggests that linkage conditionally dependent occupancy. We studied all substitutions at position 334 K(ir)6.2deltaC26 express Xenopus...