A5086493784- RNA Interference and Gene Delivery
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Lipid Membrane Structure and Behavior
- Cellular transport and secretion
- Pregnancy and preeclampsia studies
- Virus-based gene therapy research
- Nanoparticle-Based Drug Delivery
- Advanced biosensing and bioanalysis techniques
- Immune Cell Function and Interaction
- Erythrocyte Function and Pathophysiology
- RNA and protein synthesis mechanisms
- Nanowire Synthesis and Applications
- T-cell and B-cell Immunology
- Nanoplatforms for cancer theranostics
- Biochemical and Structural Characterization
- Viral Infectious Diseases and Gene Expression in Insects
- SARS-CoV-2 and COVID-19 Research
- Drug Transport and Resistance Mechanisms
- Reproductive System and Pregnancy
- 3D Printing in Biomedical Research
- CRISPR and Genetic Engineering
- Protein Structure and Dynamics
- Cellular Mechanics and Interactions
- Phagocytosis and Immune Regulation
University of Pennsylvania
2023-2025
California University of Pennsylvania
2025
The University of Texas at Austin
2019-2021
Ionizable lipid nanoparticles (LNPs) are the most clinically advanced nonviral platform for mRNA delivery. While they have been explored applications including vaccines and gene editing, LNPs not investigated placental insufficiency during pregnancy. Placental is caused by inadequate blood flow in placenta, which results increased maternal pressure restricted fetal growth. Therefore, improving vasodilation placenta can benefit both health. Here, we engineered ionizable delivery to with...
Abstract With six therapies approved by the Food and Drug Association, chimeric antigen receptor (CAR) T cells have reshaped cancer immunotherapy. However, these rely on ex vivo viral transduction to induce permanent CAR expression in cells, which contributes high production costs long‐term side effects. Thus, this work aims develop an cell engineering platform streamline while using mRNA transient, tunable expression. Specifically, ionizable lipid nanoparticle (LNP) is utilized as platforms...
Lipid nanoparticles (LNPs) are a potent delivery technology that have made it possible for the recent clinical breakthroughs in mRNA therapeutics and vaccines. A key challenge to broader implementation of vaccines is development produce precisely defined LNP formulations, with throughput can scale from discovery commercial manufacturing meet stringent standards pharmaceutical industry. To address these challenges, we developed microfluidic chip incorporates 1×, 10×, or 256× LNP-generating...
Abstract Chimeric antigen receptor (CAR) T cell therapy has achieved remarkable clinical success in the treatment of hematological malignancies. However, producing these bespoke cancer‐killing cells is a complicated ex vivo process involving leukapheresis, artificial activation, and CAR construct introduction. The activation step requires engagement CD3/TCR CD28 vital for transfection differentiation. Though antigen‐presenting (APCs) facilitate vivo, relies on antibodies against CD3...
The ability of proteins to sense membrane curvature is essential for the initiation and assembly curved structures. Established mechanisms sensing rely on with specific structural features. In contrast, it has recently been discovered that intrinsically disordered proteins, which lack a defined three-dimensional fold, can also be potent sensors curvature. How an unstructured protein structure surface? Many associate membranes have two key physical features: high degree conformational entropy...
Lipid nanoparticles (LNPs) have emerged as a viable, clinically-validated platform for the delivery of mRNA therapeutics. LNPs been utilized systems applications including vaccines, gene therapy, and cancer immunotherapy. However, LNPs, which are typically composed ionizable lipids, cholesterol, helper lipid-anchored polyethylene glycol, often traffic to liver limits therapeutic potential platform. Several approaches proposed resolve this tropism such post-synthesis surface modification or...
Introduction: Immunotherapy has revolutionized cancer treatment by harnessing the immune system to enhance antitumor responses while minimizing off-target effects. Among promising cancer-specific therapies, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) attracted significant attention. Methods: Here, we developed an ionizable lipid nanoparticle (LNP) platform deliver TRAIL mRNA (LNP-TRAIL) directly microenvironment (TME) induce cell death. Our LNP-TRAIL was formulated via...
Monogenic blood diseases are among the most common genetic disorders worldwide. These result in significant pediatric and adult morbidity, some can death prior to birth. Novel ex vivo hematopoietic stem cell (HSC) gene editing therapies hold tremendous promise alter therapeutic landscape but not without potential limitations. In offer a potentially safer more accessible treatment for these hindered by lack of delivery vectors targeting HSCs, which reside difficult-to-access bone marrow...
During healthy pregnancy, the placenta develops to allow for exchange of nutrients and oxygen between mother fetus. However, placental dysregulation can lead several pregnancy disorders, such as preeclampsia fetal growth restriction. Recently, lipid nanoparticle (LNP)-mediated delivery messenger RNA (mRNA) has been explored a promising approach treat these disorders. Here, iterative libraries LNPs with varied excipient molar ratios are screened in vitro enhanced mRNA cells minimal...
Abstract Chimeric antigen receptor (CAR) monocyte and macrophage therapies are promising solid tumor immunotherapies that can overcome the challenges facing conventional CAR T cell therapy. mRNA lipid nanoparticles (mRNA‐LNPs) offer a viable platform for in situ engineering of monocytes with transient tunable expression to reduce off‐tumor toxicity streamline manufacturing. However, identifying LNPs tropism intracellular delivery potency is difficult using traditional screening techniques....
Immune modulation through the intracellular delivery of nucleoside-modified mRNA to immune cells is an attractive approach for in vivo immunoengineering, with applications infectious disease, cancer immunotherapy, and beyond. Lipid nanoparticles (LNPs) have come fore as a promising nucleic acid platform, but LNP design criteria remain poorly defined, making rate-limiting step discovery screening process. In this study, we employed high-throughput based on molecular barcoding investigate...
Chimeric antigen receptor (CAR) cell therapy represents a hallmark in cancer immunotherapy, with significant clinical results the treatment of hematological tumors. However, current approved methods to engineer T cells express CAR use viral vectors, which are integrative and have been associated severe adverse effects due constitutive expression CAR. In this context, non-viral vectors such as ionizable lipid nanoparticles (LNPs) arise an alternative transient CAR.Here, we formulated...
Cell-based therapies for autoimmune diseases have gained significant traction, with several approaches centered around the regulatory T (Treg) cell─a well-known immunosuppressive cell characterized by its expression of transcription factor Foxp3. Unfortunately, due to low numbers Treg cells available in circulation, harvesting and culturing remains a challenge. It has been reported that engineering Foxp3 CD4+ can result Treg-like phenotype; however, current methods inefficient these cells....
It is well established that the physicochemical properties of lipid nanoparticles (LNPs) can govern their interactions with various biological barriers. One property hypothesized to influence nanoparticle-cell elasticity. Here, we formulate LNPs naturally occurring cholesterol analogs tune LNP elasticity and study its role on mRNA delivery placenta. was measured via atomic force microscopy where these exhibited Young's moduli ranging from 71.0 ± 26.2 411.4 145.7 kPa. In vitro screening in...
Cellular membranes undergo remodeling during many cellular processes including endocytosis, cytoskeletal protrusion, and organelle biogenesis. During these events, specialized proteins sense amplify fluctuations in membrane curvature to create stably curved architectures. Amphiphysin1 is a multi-domain protein containing an N-terminal crescent-shaped BAR (Bin/Amphiphysin/Rvs) domain C-terminal that largely disordered. When studied isolation, the of senses generates tubules. However,...
ABSTRACT The ability of proteins to sense membrane curvature is essential diverse remodeling processes including clathrin-mediated endocytosis. Multiple adaptor within the clathrin pathway have been shown assemble together at curved sites, leading local recruitment coat. Because does not bind directly, it has remained unclear whether plays an active role in sensing or passively recruited by its proteins. Using a synthetic tag directly on surfaces, here we show that strong sensor curvature,...