A5049410535- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Head and Neck Cancer Studies
- DNA and Nucleic Acid Chemistry
- Protein Structure and Dynamics
- RNA Research and Splicing
- Cancer-related molecular mechanisms research
- Prostate Cancer Treatment and Research
- Cancer-related Molecular Pathways
- Prostate Cancer Diagnosis and Treatment
- Mosquito-borne diseases and control
- Radiomics and Machine Learning in Medical Imaging
- Advanced biosensing and bioanalysis techniques
- Electrostatics and Colloid Interactions
- Kruppel-like factors research
- Cancer Genomics and Diagnostics
- Diabetes Treatment and Management
- Various Chemistry Research Topics
- Neuropeptides and Animal Physiology
- Insect symbiosis and bacterial influences
- Molecular Biology Techniques and Applications
- Epigenetics and DNA Methylation
- Enzyme Structure and Function
- Lipid metabolism and biosynthesis
- Dermatological and Skeletal Disorders
Yonsei University
2019-2025
University Hospitals of Leicester NHS Trust
2024
National Cancer Centre Singapore
2020-2023
Duke-NUS Medical School
2020-2023
National University of Singapore
2021
Agency for Science, Technology and Research
2013-2019
Bioinformatics Institute
2013-2019
Amazon (United States)
2018
Stanford University
2008-2012
Stanford Synchrotron Radiation Lightsource
2009
Short single-stranded nucleic acids are ubiquitous in biological processes; understanding their physical properties provides insights to acid folding and dynamics. We used small-angle x-ray scattering study 8--100 residue homopolymeric DNAs solution, without external forces or labeling probes. Poly-T's structural ensemble changes with increasing ionic strength a manner consistent polyelectrolyte persistence length theory that accounts for molecular flexibility. For any number of residues,...
Abstract Dengue (DENV) and Zika (ZIKV) viruses are clinically important members of the Flaviviridae family with an 11 kb positive strand RNA genome that folds to enable virus function. Here, we perform structure interaction mapping on four DENV ZIKV strains inside virions in infected cells. Comparative analysis SHAPE reactivities across serotypes nominates potentially functional regions highly structured, conserved, contain low synonymous mutation rates. Interaction by SPLASH identifies many...
Protein alpha-helices are ubiquitous secondary structural elements, seldom considered to be stable without tertiary contacts. However, amino acid sequences in proteins that based on alternating repeats of four glutamic (E) residues and positively charged residues, a combination arginine (R) lysine (K), have been shown form few proteins, the absence interactions. Here, we find this ER/K motif is more prevalent than previously reported, being represented diverse function from archaea humans....
RNA molecules play integral roles in gene regulation, and understanding their structures gives us important insights into biological functions. Despite recent developments template-based parameterized energy functions, the structure of RNA—in particular nonhelical regions—is still difficult to predict. Knowledge-based potentials have proven efficient protein prediction. In this work, we describe two differentiable knowledge-based derived from a curated data set structures, with all-atom or...
Alzheimer's disease (AD) and type 2 diabetes mellitus (T2D) share common features, including insulin resistance. Brain resistance has been implicated as a key factor in the pathogenesis of AD. Recent studies have demonstrated that anti-diabetic drugs sodium-glucose cotransporter-2 inhibitor (SGLT2-i) dipeptidyl peptidase-4 (DPP4-i) improve sensitivity provide neuroprotection. However, effects these two inhibitors on brain metabolism remain uninvestigated. We developed T2D-AD mouse model...
One major obstacle to membrane protein structure determination is the selection of a detergent micelle that mimics native lipid bilayer. Currently, detergents are selected by exhaustive screening because effects protein−detergent interactions on poorly understood. In this study, and dynamics an integral in different investigated nuclear magnetic resonance (NMR) electron paramagnetic (EPR) spectroscopy small-angle X-ray scattering (SAXS). The results suggest matching dimensions protein's...
Riboswitches are gene-regulating RNAs that usually found in the 5′-untranslated regions of messenger RNA. As sugar-phosphate backbone RNA is highly negatively charged, folding and ligand-binding interactions riboswitches strongly dependent on presence cations. Using small angle X-ray scattering (SAXS) hydroxyl radical footprinting, we examined cation dependence different stages glycine-binding riboswitch from Vibrio cholerae . We partial tandem aptamer this absence glycine supported by all...
Abstract Objective Treatment efficacy of androgen deprivation therapy with radical prostatectomy for intermediate- to high-risk prostate cancer is less well-studied. The NEAR trial a single-arm, phase II investigation neoadjuvant apalutamide monotherapy and (RP) in the treatment D’Amico (NCT03124433). Materials methods Patients histologically-proven, adenocarcinoma received 240 mg once-daily 12 weeks followed by RP + /−lymphadenectomy. Primary outcome was pathological complete response (pCR)...
We develop a unique algorithm implemented in the program MOSAICS (Methodologies for Optimization and Sampling Computational Studies) that is capable of nanoscale modeling without compromising resolution interest. This achieved by with customizable hierarchical degrees freedom, thereby circumventing major limitations conventional molecular modeling. With emergence RNA-based nanotechnology, large RNAs all-atom representation are used here to benchmark our algorithm. Our method locates all...
RNA folding is enabled by interactions between the nucleic acid and its ion atmosphere, mobile sheath of aqueous ions that surrounds stabilizes it. Understanding atmosphere requires interplay experiment theory. However, even an apparently simple to probe measuring dependence DNA duplex stability upon concentration identity, suffers from substantial complexity, because unfolded ensemble contains many conformational states are difficult treat accurately with To minimize this limitation, we...
The Hippo signaling pathway, which is implicated in the regulation of organ size, has emerged as a potential target for development cancer therapeutics. YAP, TAZ (transcription co-activators) and TEAD factor) are downstream transcriptional machinery effectors pathway. Formation YAP/TAZ-TEAD complex leads to transcription growth-promoting genes. Conversely, disrupting interactions decreases cell proliferation. Herein, we screened 1000-member fragment library using Thermal Shift Assay...
HDM2 binds to the p53 tumour suppressor and targets it for proteosomal degradation. Presently in clinical trials, small molecule Nutlin-3A competitively abrogates its repressive function. Using a novel vitro selection methodology, we simulated emergence of resistance by evolving mutants capable binding presence Nutlin concentrations that inhibit wild-type HDM2-p53 interaction. The phenotypes were recapitulated ex vivo assays measuring both transactivation function direct p53-HDM2 interaction...
Bevacizumab is used in the treatment of radiation necrosis (RN), which a debilitating toxicity following head and neck radiotherapy. However, there no biomarker to predict if patient would respond bevacizumab.We aimed develop cluster-based radiomics approach characterize spatial heterogeneity RN map their responses bevacizumab.118 consecutive nasopharyngeal carcinoma patients diagnosed with were enrolled. We divided 152 lesions from into 101 for training, 51 validation. extracted voxel-level...
RNA often folds hierarchically, so that its sequence defines secondary structure (helical base-paired regions connected by single-stranded junctions), which subsequently tertiary fold. To preserve base-pairing and chain connectivity, the three-dimensional conformations can explore are strongly confined compared to when constraints not enforced. Using three examples, we studied how confines dictates an RNA’s preferred conformations. We made use of Macromolecular Conformations SYMbolic...
R248 in the DNA binding domain (DBD) of p53 interacts directly with minor groove DNA. Earlier nuclear magnetic resonance (NMR) studies indicated that R248Q mutation resulted conformation changes parts DBD far from site. However, how information propagates site to rest is still not well understood. We performed a series all-atom molecular dynamics (MD) simulations dissect sterics and charge effects on p53-DBD conformation: (i) wild-type DBD; (ii) an electrically neutral arginine side-chain;...
RNA molecules are attractive therapeutic targets because non-coding have increasingly been found to play key regulatory roles in the cell. Comparing and classifying 3D structures yields unique insights into evolution function. With rapid increase number of atomic-resolution structures, it is crucial effective tools classify investigate them for structural similarities at different resolutions. We previously developed algorithm CLICK superimpose a pair protein by clique matching least squares...
Abstract Monocytes recruitment from the blood to inflamed tissues following ischemic stroke is an important immune response wound healing and tissue repair. Mouse monocytes can be endogenously divided into two distinct populations: pro-inflammatory or classical that express CCR2 high CX3CR1 low circulate in blood, anti-inflammatory non-classical patrol locally. In this study of transgenic mice with functional GFP/+ -CCR2 RFP/+ , we found recruited injured brain were cytokine-dependently...
In the disease familial amyloidosis, Finnish type (FAF), also known as AGel amyloidosis (AGel), mechanism by which point mutations in calcium-regulated actin-severing protein gelsolin lead to furin cleavage is not understood intact protein. Here, we provide a structural and biochemical characterization of FAF variants. X-ray crystallography structures mutant gelsolins demonstrate that do significantly disrupt calcium-free conformations gelsolin. Small-angle X-ray–scattering (SAXS) studies...