A5072299025- Mass Spectrometry Techniques and Applications
- Protein Structure and Dynamics
- Clostridium difficile and Clostridium perfringens research
- Pancreatic function and diabetes
- Antimicrobial Resistance in Staphylococcus
- Viral Infectious Diseases and Gene Expression in Insects
- Advanced NMR Techniques and Applications
- Cancer, Hypoxia, and Metabolism
- NMR spectroscopy and applications
- Hippo pathway signaling and YAP/TAZ
- Photoreceptor and optogenetics research
- Toxin Mechanisms and Immunotoxins
- Cognitive Abilities and Testing
- Mental Health Research Topics
- Enzyme Structure and Function
- Cancer-related Molecular Pathways
- Biochemical and Molecular Research
- Spectroscopy and Quantum Chemical Studies
- Cell death mechanisms and regulation
- Educational and Psychological Assessments
- Genetics and Neurodevelopmental Disorders
- Advanced MRI Techniques and Applications
- Light effects on plants
- Endoplasmic Reticulum Stress and Disease
- Viral gastroenteritis research and epidemiology
The Graduate Center, CUNY
2019-2024
CUNY Advanced Science Research Center
2019-2024
Merck & Co., Inc., Rahway, NJ, USA (United States)
2024
Guangzhou Medical University
2024
City University of New York
2020-2021
Institute for Research in Immunology and Cancer
2020
Université de Montréal
2020
RASSF proteins interact with distinct GTPase partners to regulate downstream Hippo and p53 signaling.
Targeting Clostridium difficile infection is challenging because treatment options are limited, and high recurrence rates common. One reason for this that hypervirulent C. strains often have a binary toxin termed the toxin, in addition to enterotoxins TsdA TsdB. The has an enzymatic component, CDTa, pore-forming or delivery subunit CDTb. CDTb was characterized here using combination of single-particle cryoelectron microscopy, X-ray crystallography, NMR, other biophysical methods. In absence...
Biologic drugs have emerged as a rapidly expanding and important modality, offering promising therapeutic solutions by interacting with previously 'undruggable' targets, thus significantly the range of modern pharmaceutical applications. However, inherent complexity these also introduces liabilities poses challenges in their development, necessitates efficient screening methods to evaluate structural stability behavior. Although NMR spectroscopy is well-suited for detecting weak...
Transcription factors are challenging to target with small-molecule inhibitors due their structural plasticity and lack of catalytic sites. Notable exceptions include naturally ligand-regulated transcription factors, including our prior work the hypoxia-inducible factor (HIF)-2 factor, showing that binding within an internal pocket HIF-2α Per-Aryl hydrocarbon Receptor Nuclear Translocator (ARNT)-Sim (PAS)-B domain can disrupt its interactions dimerization partner, ARNT. Here, we explore...
Abstract Small molecule binding within internal cavities provides a way to control protein function and structure, as exhibited in numerous natural artificial settings. Unfortunately, most ways identify suitable require high-resolution structures priori may miss potential cryptic sites. Here we address this limitation via high-pressure solution NMR spectroscopy, taking advantage of the distinctive nonlinear pressure-induced chemical shift changes observed proteins containing voids. We...
Recent research on fold-switching metamorphic proteins has revealed some notable exceptions to Anfinsen's hypothesis of protein folding. We have previously described how a single point mutation can enable well-folded domain, one the two PAS (Per-ARNT-Sim) domains human ARNT (aryl hydrocarbon receptor nuclear translocator) protein, interconvert between conformers related by slip an internal β-strand. Using this as test case, we advance concept "fragile fold," fold that reversibly rearrange...
Objective To test the psychometric properties of Chinese version biological rhythms interview assessment in neuropsychiatry (C-BRIAN) a group young adults with and without depressive symptoms. Methods Three hundred seventy-eight university students were recruited as participants. Based on scores from Center for Epidemiological Survey Depression Scale (CES-D), divided into depressed healthy group. Explorative factor analysis was applied to assess construct validity C-BRIAN. The Pittsburgh...
Biologic drugs have emerged as a rapidly expanding and important modality, offering promising therapeutic solutions by interacting with previously "undruggable" targets, thus significantly the range of modern pharmaceutical applications. However, inherent complexity these also introduces liabilities poses challenges in their development, necessitating efficient screening methods to evaluate structural stability behavior. Although nuclear magnetic resonance (NMR) spectroscopy is well-suited...
Abstract Transcription factors are generally challenging to target with small molecule inhibitors due their structural plasticity and lack of catalytic sites. Notable exceptions include several naturally ligand-regulated transcription factors, including our prior work the heterodimeric HIF-2 factor which showed that binding within an internal pocket HIF-2α PAS-B domain can disrupt its interactions dimerization partner, ARNT. Here, we explore feasibility similarly targeting molecules...
Abstract Activated RAS GTPases signal by directly binding effector proteins. Effectors have a folded association (RA) domain that binds exclusively to GTP-loaded RAS, but the specificity of most RA domains for >150 superfamily is unknown. Ten RAS-association family (RASSF) proteins comprise largest group effectors, proposed couple pro-apoptotic Hippo pathway. We show RASSF1-6 complex with kinase, while RASSF7-10 are separate related p53-regulatory ASPP effectors. Only RASSF5 activated...
ABSTRACT Proteins often interconvert between different conformations in ways critical to their function. While manipulating such equilibria for biophysical study is challenging, the application of pressure a potential route achieve control by favoring population lower volume states. Here, we use this feature interconversion ARNT PAS-B Y456T, which undergoes dramatic beta-strand slip as it switches two stably-folded conformations. Coupling high and biomolecular NMR, obtained first...
MACROMOLECULES C196separate enzymes ATP sulfurylase and APS kinase, respectively.In humans both activities are present on single polypeptide chain giving bifunctional PAPS synthetase.We have done extensive structural analysis to understand what the implications of having one chain.Is product first reaction directly transferred active site second reaction?Are two reactions coordinated?If so, how sites communicate?Here we report 2.1 Å crystal structures domain human synthetase in complex with...
Abstract Targeting Clostridium difficile infection (CDI) is challenging because treatment options are limited, and high recurrence rates common. One reason for this that hypervirulent CDI often has a binary toxin termed the C. (CDT), in addition to enterotoxins TsdA TsdB. CDT an enzymatic component, CDTa, pore-forming or delivery subunit CDTb. CDTb was characterized here using combination of single particle cryoEM, X-ray crystallography, NMR, other biophysical methods. In absence two novel...
Abstract. Recent research on fold-switching metamorphic proteins has revealed some notable exceptions to Anfinsen's hypothesis of protein folding. We have previously described how a single point mutation can enable well-folded domain, one the two PAS (Per-ARNT-Sim) domains human ARNT (aryl hydrocarbon receptor nuclear translocator) protein, interconvert between conformers related by slip an internal beta-strand. Using this as test case, we advance concept fragile fold, fold that reversibly...