A5070307998- Cancer Treatment and Pharmacology
- Advanced Breast Cancer Therapies
- Colorectal Cancer Treatments and Studies
- Material Dynamics and Properties
- Protein Degradation and Inhibitors
- Computational Drug Discovery Methods
- Pickering emulsions and particle stabilization
- Cancer Genomics and Diagnostics
- Surfactants and Colloidal Systems
- Immune cells in cancer
- Ferroptosis and cancer prognosis
- Glioma Diagnosis and Treatment
- Ubiquitin and proteasome pathways
- Cancer Immunotherapy and Biomarkers
- bioluminescence and chemiluminescence research
- Redox biology and oxidative stress
- Multiple Myeloma Research and Treatments
- Electrostatics and Colloid Interactions
- Bioinformatics and Genomic Networks
- Block Copolymer Self-Assembly
- Lung Cancer Treatments and Mutations
- HER2/EGFR in Cancer Research
- Cellular Mechanics and Interactions
- Polymer Surface Interaction Studies
- Spectroscopy and Quantum Chemical Studies
The University of Texas MD Anderson Cancer Center
2019-2024
Center for Theoretical Biological Physics
2015-2017
Rice University
2015-2017
Columbia University
2010-2013
Institute for Atomic and Molecular Physics
2007-2008
Background and Aims Cholangiocarcinoma (CCA) is a deadly highly therapy‐refractory cancer of the bile ducts, with early results from immune checkpoint blockade trials showing limited responses. Whereas recent molecular assessments have made bulk characterizations profiles their genomic correlates, spatial may reveal actionable insights. Approach Results Here, we integrated checkpoint‐directed immunohistochemistry next‐generation sequencing resected intrahepatic CCA samples 96 patients. We...
We demonstrate that the self-assembly of spherical nanoparticles (NPs), grafted isotropically with polymeric ligands, into anisotropic structures is a manifestation fluctuations inherent in small number statistics. Computer simulations show organization ligand atoms around an individual NP not spatially isotropic for numbers grafts and monomers. This inherent, asymmetric distribution causes effective, two-body inter-NP potential to have strong orientational dependence, which reproduces...
Abstract Cancer cells depend on multiple driver alterations whose oncogenic effects can be suppressed by drug combinations. Here, we provide a comprehensive resource of precision combination therapies tailored to coalterations that are recurrent across patient cohorts. To generate the resource, developed Recurrent Features Leveraged for Combination Therapy (REFLECT), which integrates machine learning and cancer informatics algorithms. Using multiomic data, method maps coalteration signatures...
Small bowel adenocarcinoma (SBA) is a rare malignancy marked with poor prognosis. The cellular and proteomic heterogeneity within the tumor immune microenvironment (TIME) of SBA likely driver prognosis, disease progression response to therapy. We have addressed major gap in knowledge TIME using highly multiplexed, protein imaging tumor-immune ecosystem generating comprehensive, single-cell level, spatial, atlas > 600,000 cells from 136 matched normal samples clinically genomically...
The interactions between tumor intrinsic processes and immune checkpoints can mediate evasion by cancer cells responses to immunotherapy. It is, however, challenging identify functional due the prohibitively complex molecular landscape of tumor-immune interfaces. We address this challenge with a statistical analysis framework, immuno-oncology gene interaction maps (ImogiMap). ImogiMap quantifies statistically validates checkpoint based on their co-associations immune-associated phenotypes....
We report extensive simulations of the relaxation dynamics a self-avoiding polymer confined inside cylindrical pore. In particular, we concentrate on examining how confinement influences scaling behavior global time chain, tau, with chain length N and pore diameter D. An earlier analysis based de Gennes blob picture led to tau approximately N(2)D(13). Our numerical effort that combines molecular Monte Carlo simulations, however, consistently produces different results for up 2000. argue...
We studied the aggregation of 1 µm colloids bridged by DNA with 32 contour length. mixed two species particles grafted double-stranded λ-DNA displaying short, complementary single-stranded 'overhangs' as free binding-ends. Confocal microscopy showed formation stable, size-limited clusters in which were at touching contact. Simulations suggest that observed close contact and limitation to grow both result from entropic exclusion bridging space between nearby particle surfaces.
We report a Monte Carlo study of 1 : binary mixture particles coated with DNA chains "sticky" ends. The system was modeled using coarse-grained representation. In order to map out the phase diagram this model we combined biased simulations histogram reweighting techniques. find that, at low temperatures (strong hybridization) undergoes separation between dilute vapor-like and dense network-forming liquid-like phase. observe surprising non-monotonic dependence coexistence pressure on...
We use computer simulations to investigate the stability of a two-component polymer brush de-mixing on curved template into phases different morphological properties. It has been previously shown via molecular dynamics that immiscible chains having length and anchored cylindrical will phase separate stripes widths oriented perpendicularly axis. calculate free energy differences for variety stripe widths, extract simple relationships between sizes two polymers, N(1) N(2), dependence width....
We report grand-canonical Monte Carlo simulations of an equimolar mixture hard colloids coated with long polymers that have a complementary functionalization. Such systems the potential to function as self-healing materials. Under conditions where polymer ends are strongly associated, we observe first-order vapor-liquid transition from dilute gas colloidal dimers dense, liquidlike phase. This is driven exclusively by increase in entropy associated bond disorder---an effect was predicted...
Abstract The development of effective targeted therapies for the treatment basal-like breast cancers remains challenging. Here, we demonstrate that BET inhibition induces a multi-faceted adaptive response program leading to MCL1 protein-driven evasion apoptosis in cancers. Consequently, co-targeting and is highly synergistic vitro vivo cancer models. Drug genomics analyses revealed copy number alterations, including low-level gains, are selectively enriched associated with co-targeting....
We report molecular dynamics simulations of a system repulsive, polymer-tethered colloidal particles. use an explicit polymer model to explore how the length and behavior (ideal or self-avoiding) affect ability particles organize into ordered structures when is compressed moderate volume fractions. find variety different phases whose origin can be explained in terms configurational entropy polymers colloids. Finally, we discuss compare our results those obtained for similar systems using...
We use numerical simulations to study the phase behavior of a system purely repulsive soft dumbbells as function size ratio two components and their relative degree deformability. find plethora different phases, which includes most mesophases observed in self-assembly block copolymers but also crystalline structures formed by asymmetric, hard binary mixtures. Our results detail phenomenological these systems when softness is introduced terms classes interparticle interactions: (a) elastic...
Fundamental biological processes of development tissues and organs in multicellular organisms are governed by various signaling molecules, which called morphogens. It is known that spatial temporal variations the concentration profiles frequently referred as morphogen gradients, lead to a cell differentiation via activating specific genes concentration-dependent manner. widely accepted establishment gradients involves multiple biochemical reactions diffusion processes. One critical elements...
Successful biological development via spatial and temporal regulations of cell differentiation relies on the action multiple signaling molecules that are known as morphogens. It is now well established create nonuniform concentration profiles, called morphogen gradients, activate different genes, leading to patterning in developing organisms. The current view formation gradients it a result complex reaction-diffusion processes include production, diffusion, degradation molecules. Recent...
We use numerical simulations to study the crystallization of monodisperse systems hard aspherical particles. find that particle shape and crystallizability can be easily related each other when particles are characterized in terms two simple experimentally accessible order parameters: one based on surface-to-volume ratio angular distribution perturbations away from ideal spherical shape. present a phase diagram obtained by exploring 487 different shapes across two-order-parameter spectrum....
Therapeutic options for treatment of basal-like breast cancers remain limited. Here, we demonstrate that bromodomain and extra-terminal (BET) inhibition induces an adaptive response leading to MCL1 protein-driven evasion apoptosis in cancer cells. Consequently, co-targeting BET is highly synergistic models. The mechanism involves the upregulation lipid synthesis enzymes including rate-limiting stearoyl-coenzyme A (CoA) desaturase. Changes pathway are associated with increases cell motility...
Abstract Small bowel adenocarcinoma (SBA) is a rare malignancy associated with poor prognosis. The cellular and proteomic heterogeneity within the tumor immune microenvironment (TIME) of SBA likely driver prognosis, disease progression response to therapy. There is, however, major gap in our knowledge interactions SBA. Cyclic Immunofluorescence (CycIF), an antibody-based, highly multiplexed imaging technology for spatially resolved single cell level profiling, well suited map organization...
Abstract Resolving tissue and proteomic heterogeneity is critical to decoding the structure function of tumor-immune microenvironment (TIME). Such understanding requires profiling tumor immune cell features with spatial resolution at single-cell level. Although such spatially resolved methods data sets are becoming increasingly available, analytical computational that can extract highly complex interactions within TIME lacking. To address problem, we have developed a pipeline call Spatial...
<title>Abstract</title> <bold>Background</bold>. Interactions among tumor, immune, and vascular niches play major roles in driving glioblastoma (GBM) malignancy treatment responses. The composition, heterogeneity, localization of extracellular core matrix proteins (CMPs) that mediate such interactions, however, are not well understood. <bold>Methods</bold>. Here, through computational genomics proteomics approaches, we analyzed the functional clinical relevance CMP expression GBM at bulk,...
Gastrulation is a fundamental phase during the biological development of most animals when single layer identical embryo cells transformed into three-layer structure, from which organs start to develop. Despite remarkable progress in quantifying gastrulation processes, molecular mechanisms these processes remain not well understood. Here we theoretically investigate early spatial patterning geometrically confined colony embryonic stem cells. Using reaction-diffusion model, role...
Abstract It is challenging to identify the tumor-immune system interactions that modulate immune states and immunotherapy responses due prohibitively complex space of possible interactions. Our statistical analysis framework, ImogiMap quantifies based on their synergistic co-associations with immune-associated phenotypes. ImogiMap-based analyses recapitulated known modulating nominated CD86/CD70 axis as an target overlaps IFNG overexpression patient survival in endometrial carcinoma.