A5044408095- Force Microscopy Techniques and Applications
- Cell Adhesion Molecules Research
- Digitalization, Law, and Regulation
- RNA Interference and Gene Delivery
- Cellular Mechanics and Interactions
- Advanced Fluorescence Microscopy Techniques
- Law and Political Science
- Advanced biosensing and bioanalysis techniques
- Immunotherapy and Immune Responses
- Diverse Legal and Medical Studies
- Monoclonal and Polyclonal Antibodies Research
- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
- Immune Cell Function and Interaction
- Photochromic and Fluorescence Chemistry
- Advanced Biosensing Techniques and Applications
- T-cell and B-cell Immunology
- DNA and Nucleic Acid Chemistry
- Nanoplatforms for cancer theranostics
- Immune cells in cancer
- Chemokine receptors and signaling
- Adipokines, Inflammation, and Metabolic Diseases
- Cancer, Hypoxia, and Metabolism
- Neural Networks Stability and Synchronization
- Intellectual Property Rights and Media
Georgia Institute of Technology
2019-2024
The Wallace H. Coulter Department of Biomedical Engineering
2019-2024
Emory University
2020-2022
University of Wisconsin–Madison
2020
Madison Group (United States)
2020
Significance To defend against cancer and viral infections, the T cell receptor (TCR) must recognize antigens on surface of target cells. TCR antigen recognition involves transmission forces which are often weak, infrequent, short lived, hence difficult to study. We solve this challenge by developing molecular probes that store mechanical information. This approach reveals when encountering different antigens, sampling is correlated with potency. Since coreceptors heavily involved in tuning...
T cells defend against cancer and viral infections by rapidly scanning the surface of target seeking specific peptide antigens. This key process in adaptive immunity is sparked upon cell receptor (TCR) binding antigens within cell-cell junctions stabilized integrin (LFA-1)/intercellular adhesion molecule–1 (ICAM-1) complexes. A long-standing question this area whether forces transmitted through LFA-1/ICAM-1 complex tune signaling. Here, we use spectrally encoded DNA tension probes to reveal...
Obesity is a major public health crisis given its rampant growth and association with an increased risk for cancer. Interestingly, patients obesity tend to have tumor burden decreased T-cell function. It remains unclear how compromises mediated immunity. To address this question, we modeled the adipocyte niche using secretome released from adipocytes as well of stromal cells investigated these factors modulated We found that secretomes altered antigen-specific receptor (TCR) triggering...
Abstract Many cellular processes, including cell division, development, and migration require spatially temporally coordinated forces transduced by cell-surface receptors. Nucleic acid-based molecular tension probes allow one to visualize the piconewton (pN) applied these Building on this technology, we recently developed force microscopy (MFM) which uses fluorescence polarization map receptor orientation with diffraction-limited resolution (~250 nm). Here, show that structured illumination...
Mechanical forces transmitted at the junction between two neighboring cells and extracellular matrix are critical for regulating many processes ranging from development to immunology. Therefore, developing tools study these molecular scale is critical. Our group developed a suite of tension sensors quantify visualize generated by specific ligands. The most sensitive class comprised nucleic acid stem-loop hairpins. These use fluorophore-quencher pairs report on mechanical extension unfolding...
Cytokine signaling is challenging to study and therapeutically exploit as the effects of these proteins are often pleiotropic. A subset cytokines can, however, achieve signal specificity via association with latency-inducing proteins, which cage cytokine until disrupted by discreet biological stimuli. Inspired this precision, here, we describe a strategy for synthetic induction latency modification photolabile polymers that mimic while attached then restore protein activity in response...
Global Learning Algorithms presented in a companion paper are applied to practical classification and segmentation problems: Texture Classification Segmentation of artificial natural textures, Text as sub-problem Page Layout Analysis. In all cases, DTCNN systems can solve the problem very well spite its only local interconnection structure.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Prolonged and elevated transforming growth factor-β1 (TGF-β1) signaling can lead to undesired scar formation during tissue repair fibrosis that is often a result of chronic inflammation in the lung, kidney, liver, heart, skin, joints. We report new TGF-β1 binding peptides interfere with its cognate receptors thus attenuate biological activity. identified from domains TGF-β engineered their sequences facilitate chemical conjugation biomaterials using molecular docking simulations. The vitro...
Abstract Background Immune checkpoint inhibitors (ICI) have revolutionized cancer treatment. Unfortunately, existing FDA approved biomarkers do not accurately predict which patients will respond. The Elephas Cybrid™ platform aims to improve ICI response prediction by imaging a patient’s biopsy treated with ex vivo. Multiphoton microscopy (MPM) is powerful technique interrogate the biological changes in live tumor fragments (LTFs) following MPM allows rapid visualization of processes 3D...
SignificanceTo enable non-destructive longitudinal assessment of drug agents in intact tumor tissue without the use disruptive probes, we have designed a label-free method to quantify health individual cells excised using multiphoton fluorescence lifetime imaging microscopy (MP-FLIM).AimUsing murine fragments which preserve native microenvironment, seek demonstrate signals generated by intrinsically fluorescent metabolic co-factors nicotinamide adenine dinucleotide phosphate [NAD(P)H] and...
<h3>Background</h3> We are developing a novel diagnostic platform as there is an unmet need to guide immunotherapy treatment for cancer patients. The Elephas uses live tumor fragments (LTFs), thereby preserving the native microenvironment ex-vivo. utilizes advanced imaging and molecular assays functionally measure effect of on immune cells. A significant challenge associated with such obtaining human specimens that from known clinical responders/non-responders immunotherapy. Thus, we...
Immune checkpoint blockade targeting PD-1 shows great success in cancer therapy. However, the mechanism of how ligand binding initiates signaling remains unclear. As prognosis markers multiple cancers, soluble PD-L1 is found patient sera and can bind PD-1, but fails to suppress T cell function. This our previous observations that cells exert endogenous forces on PD-1-PD-L2 bonds prompt hypothesis mechanical force might be critical triggering, which missing case due lack support afforded by...
Abstract Integrin receptors transduce the mechanical properties of extracellular matrix. Past studies using DNA probes showed that integrins sense magnitude ligand forces with pN resolution. An open question is whether integrin also force-extension trajectory their ligands. The challenge in addressing this pertains to lack molecular can control trajectories independently force magnitude. To address limitation, we synthesized two reversible fold identical self-complementary domains but...
Mechanical forces transmitted at the junction between two neighboring cells and extracellular matrix are critical for regulating many processes ranging from development to immunology. Therefore, developing tools study these molecular scale is critical. Our group developed a suite of tension sensors quantify visualize generated by specific ligands. The most sensitive class comprised nucleic acid stem-loop hairpins. These use fluorophore-quencher pairs report on mechanical extension unfolding...
<h3>Background</h3> Immune Checkpoint Inhibitors (ICI) have revolutionized cancer treatment. Unfortunately, existing FDA approved biomarkers like PD-L1, MSI and dMMR do not accurately predict which patients will respond. The Elephas Cybrid™ platform aims to improve ICI response prediction using multiple biological assays imaging of the patient's live tumor fragments (LTF)™ treated with <i>ex vivo</i>. Multiphoton microscopy (MPM) is a powerful technique one primary modalities uses...
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