A5027352925- Cancer Immunotherapy and Biomarkers
- Ion channel regulation and function
- Inflammatory mediators and NSAID effects
- Computational Drug Discovery Methods
- Immunotherapy and Immune Responses
- vaccines and immunoinformatics approaches
- T-cell and B-cell Immunology
- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Cardiac electrophysiology and arrhythmias
- Electrochemical Analysis and Applications
- Monoclonal and Polyclonal Antibodies Research
- Mass Spectrometry Techniques and Applications
- Nanopore and Nanochannel Transport Studies
- Estrogen and related hormone effects
- Neuroscience and Neural Engineering
- Single-cell and spatial transcriptomics
- Cell Image Analysis Techniques
- Domain Adaptation and Few-Shot Learning
- Data Mining Algorithms and Applications
- NMR spectroscopy and applications
- CRISPR and Genetic Engineering
- Inflammatory Biomarkers in Disease Prognosis
- Imbalanced Data Classification Techniques
- Machine Learning and Data Classification
The University of Texas Southwestern Medical Center
2017-2023
Southwestern Medical Center
2017-2021
University of Chicago
2011-2018
Potassium channels are responsible for the selective permeation of K + ions across cell membranes. permeate in single file through selectivity filter, a narrow pore lined by backbone carbonyls that compose four binding sites. Here, we report on two-dimensional infrared (2D IR) spectra semisynthetic KcsA channel with site-specific heavy ( 13 C 18 O) isotope labels filter. The ultrafast time resolution 2D IR spectroscopy provides an instantaneous snapshot multi-ion configurations and...
Abstract Immune repertoire deep sequencing allows comprehensive characterization of antigen receptor–encoding genes in a lymphocyte population. We hypothesized that this method could enable novel approach to diagnose disease by identifying receptor sequence patterns associated with clinical phenotypes. In study, we developed statistical classifiers T-cell (TCR) repertoires distinguish tumor tissue from patient-matched healthy the same organ. The basis both was biophysicochemical motif...
C-type inactivation is a time-dependent process observed in many K+ channels whereby prolonged activation by an external stimulus leads to reduction ionic conduction. While thought be result of constriction the selectivity filter, local dynamics remain elusive. Here, we use molecular (MD) simulations KcsA channel elucidate nature kinetically delayed activation/inactivation gating coupling. Microsecond-scale MD based on truncated form (C-terminal domain deleted) provide first glimpse onset...
Recovery in K(+) channels, that is, the transition from inactivated nonconductive selectivity filter conformation toward conductive conformation, occurs on a time scale of order seconds, which is astonishingly long, given structural differences among conformations are faint (<1 Å). Computational studies and electrophysiological measurements suggested buried water molecules bound behind at origin slowness recovery channels. Using combination solid-state NMR spectroscopy (ssNMR) long molecular...
Background: Recent technological advances in immune repertoire sequencing have created tremendous potential for advancing our understanding of adaptive response dynamics various states health and disease. Immune produces large, highly complex data sets, however, which require specialized methods software tools their effective analysis interpretation. Results: VDJServer is a cloud-based portal sequence that provides access to suite complete workflow, including modules pre-processing quality...
Deep sequencing of lymphocyte receptor repertoires has made it possible to comprehensively profile the clonal composition populations. This opens door for novel approaches diagnose and prognosticate diseases with a driving immune component by identifying repertoire sequence patterns associated clinical phenotypes. Indeed, recent studies support feasibility this, demonstrating an association between repertoire-level summary statistics (e.g., diversity) patient outcomes several diseases. In...
Background Increased body mass index (BMI) has been associated with improved response to immune checkpoint inhibitors (ICIs) in multiple cancer types. We evaluated associations between BMI, ICI dosing strategy, and clinical outcomes. Methods abstracted data on patients treated ICI, including age, sex, type, strategy (weight-based or fixed), radiographic response, overall survival (OS), progression-free (PFS). compared outcomes low-BMI high-BMI populations using Kaplan-Meier curves, Cox...
Antibiotic administration is associated with worse clinical outcomes and changes to the gut microbiome in cancer patients receiving immune checkpoint inhibitors (ICI). However, effects of antibiotics on systemic function are unknown. We, therefore, evaluated antibiotic exposure, therapeutic responses, multiplex panels 40 serum cytokines 124 antibodies at baseline six weeks after ICI initiation, p < 0.05 false discovery rate (FDR) 0.2 considered significant. A total 251 were included, whom...
Population dynamics of patterned neuronal firing are fundamental to information processing in the brain. Multiphoton microscopy combination with calcium indicator dyes allows circuit be imaged single-neuron resolution. However, temporal resolution fluorescent measures is constrained by imaging frequency imposed standard raster scanning techniques. As a result, traditional scans limit ability detect relative timing action potentials population. To maximize speed fluorescence from large...
The interplay between the intracellular gate and selectivity filter underlies structural basis for gating in potassium ion channels. Using a combination of protein semisynthesis, two-dimensional infrared (2D IR) spectroscopy, molecular dynamics (MD) simulations, we probe occupancy at S1 binding site constricted state KcsA channel when is open closed. 2D IR spectra resolve two features, whose relative intensities depend on gate. By matching experiment to calculated structures predicted by MD...
Significance After opening in response to a specific stimulus, some potassium channels undergo C-type inactivation. Crystal structures of KcsA have revealed that the selectivity filter constricts under conditions associated with Functional studies based on semisynthetic either D-ala77 or amide-to-ester backbone substitutions provide important observations arguing against constricted conformation as molecular basis In this study, dynamics simulations atomic models channel are performed...
We previously showed, in a pilot study with publicly available data, that T cell receptor (TCR) repertoires from tumor infiltrating lymphocytes (TILs) could be distinguished adjacent healthy tissue by the presence of TCRs bearing specific, biophysicochemical motifs their antigen binding regions. hypothesized such might allow development novel approach to cancer detection. The were specific and achieved high classification accuracy: we found distinct for breast versus colorectal...
Most statistical classifiers are designed to find patterns in data where numbers fit into rows and columns, like a spreadsheet, but many kinds of do not conform this structure. To uncover non-conforming data, we describe an approach for modifying established handle which call dynamic kernel matching (DKM). As examples consider (i) dataset T-cell receptor (TCR) sequences labelled by disease antigen (ii) sequenced TCR repertoires patient cytomegalovirus (CMV) serostatus, anticipating that both...
Background Immune checkpoint inhibitor (ICI) therapies may cause unpredictable and potentially severe autoimmune toxicities termed immune-related adverse events (irAEs). Because T cells mediate ICI effects, cell profiling provide insight into the risk of irAEs. Here we evaluate a novel metric—the T-cell tolerant fraction—as predictor future Methods We examined receptor beta (TRB) locus sequencing from baseline pretreatment samples an institutional registry previously published studies. For...
Cervical cancer is the fourth most common and leading cause of death among women worldwide. In low Human Development Index settings, it ranks second. Screening surveillance involve cytology-based Papanicolaou (Pap) test testing for high-risk human papillomavirus (hrHPV). The Pap has sensitivity to detect precursor lesions, while a single hrHPV cannot distinguish persistent infection from one that immune system will naturally clear. Furthermore, who are hrHPV-positive progress high-grade...
e15260 Background: Immune repertoire deep sequencing allows profiling T-cell populations and enables novel approaches to diagnose prognosticate cancer by identifying receptor sequence patterns associated with clinical phenotypes outcomes. Methods: Our goal is develop a method using sequenced receptors. To determine how profile the specificity of receptor, we analyze 3D X-ray crystallographic structures receptors bound antigen. We observe contiguous strip typically 4 amino acid residues in...
<p>model weights for colorectal cancer model</p>
<p>Supplementary Table 7: Model weights for all 17 breast cancer models</p>
<p>multiple 4-mers per CDR3</p>