A5084394374- CAR-T cell therapy research
- Axon Guidance and Neuronal Signaling
- Congenital heart defects research
- Sperm and Testicular Function
- Reproductive Biology and Fertility
- Hippo pathway signaling and YAP/TAZ
- Angiogenesis and VEGF in Cancer
- Integrated Circuits and Semiconductor Failure Analysis
- Cardiac Fibrosis and Remodeling
- RNA Interference and Gene Delivery
- Immune Cell Function and Interaction
- Virus-based gene therapy research
- Advancements in Semiconductor Devices and Circuit Design
- Pancreatic function and diabetes
- Cardiac Structural Anomalies and Repair
- Immunotherapy and Immune Responses
- Congenital Heart Disease Studies
- T-cell and B-cell Immunology
- Ovarian function and disorders
- Viral Infections and Immunology Research
- Wnt/β-catenin signaling in development and cancer
- Histone Deacetylase Inhibitors Research
- Polyamine Metabolism and Applications
- Developmental Biology and Gene Regulation
- Cancer-related molecular mechanisms research
University of Pennsylvania
2014-2025
Fate Therapeutics (United States)
2025
California Institute for Regenerative Medicine
2015-2022
Fibrosis affects millions of people with cardiac disease. We developed a therapeutic approach to generate transient antifibrotic chimeric antigen receptor (CAR) T cells in vivo by delivering modified messenger RNA (mRNA) cell–targeted lipid nanoparticles (LNPs). The efficacy these vivo–reprogrammed CAR was evaluated injecting CD5-targeted LNPs into mouse model heart failure. Efficient delivery mRNA encoding the lymphocytes observed, which produced transient, effective vivo. Antifibrotic...
The plasticity of differentiated cells in adult tissues undergoing repair is an area intense research. Pulmonary alveolar type II produce surfactant and function as progenitors the adult, demonstrating both self-renewal differentiation into gas exchanging I cells. In vivo, are thought to be terminally their ability give rise alternate lineages has not been reported. Here we show that Hopx becomes restricted during development. However, unexpectedly, lineage-labelled Hopx+ proliferate...
Identifying coronary artery progenitors and their developmental pathways could inspire novel regenerative treatments for heart disease. Multiple sources of vessels have been proposed, including the sinus venosus (SV), endocardium proepicardium, but relative contributions to circulation molecular mechanisms regulating development are poorly understood. We created an ApjCreER mouse line as a lineage-tracing tool map SV-derived onto compared resulting lineage pattern with endocardial...
The use of lipid nanoparticles (LNP) to encapsulate and deliver mRNA has become an important therapeutic advance. In addition vaccines, LNP-mRNA can be used in many other applications. For example, targeting the LNP with anti-CD5 antibodies (CD5/tLNP) allow for efficient delivery payloads T cells express protein. As percentage protein expressing induced by intravenous injection CD5/tLNP is relatively low (4-20%), our goal was find ways increase mRNA-induced translation efficiency. We showed...
Ischemic heart disease resulting from myocardial infarction (MI) is the most prevalent form of in United States. Post-MI cardiac remodeling a multifaceted process that includes activation fibroblasts and complex immune response. T-regulatory cells (Tregs), subset CD4+ T cells, have been shown to suppress innate adaptive response limit deleterious following injury. However, mechanisms by which injured myocardium recruits suppressive remain largely unknown. Here, we role for Hippo signaling...
Notch signaling has well defined roles in the assembly of arterial walls and development endothelium smooth muscle vasculature. Hippo regulates cellular growth many tissues, contributes to regulation organ size, addition other functions. Here, we show that pathways converge regulate differentiation neural crest, which is critical for normal aortic arch arteries cranial vasculature during embryonic development. Neural crest specific deletion effectors Yap Taz produces precursors migrate...
Class 3 semaphorins were initially described as axonal growth cone guidance molecules that signal through plexin and neuropilin coreceptors since then have been established to be regulators of vascular development. Semaphorin 3e (Sema3e) has shown previously repel endothelial cells is the only class semaphorin known capable signaling via a receptor without coreceptor. Sema3e signals D1 (Plxnd1) regulate patterning by modulating cytoskeleton focal adhesion structures. We showed recently 3d...
Loss of Pax3, a developmentally regulated transcription factor expressed in premigratory neural crest, results severe developmental defects and embryonic lethality. Although Pax3 mutations produce profound phenotypes, the intrinsic transcriptional activation exhibited by is surprisingly modest. We postulated existence coactivators that function with to mediate functions. A high-throughput screen identified Hippo effector proteins Taz Yap65 as coactivators. Synergistic coactivation target...
Energy sources that can be metabolized to yield ATP are essential for normal sperm functions such as motility. Two major monosaccharides, sorbitol and fructose, present in semen. Furthermore, dehydrogenase (SORD) convert which then via the glycolytic pathway make ATP. Here we characterize Sord mRNA SORD expression during mouse spermatogenesis examine ability of support epididymal motility tyrosine phosphorylation. levels increased course spermatogenic differentiation. protein, however, was...
In this study, we aimed to determine the efficacy of in vivo chimeric antigen receptor (CAR) T cell therapy, generated by targeted lipid nanoparticles (t-LNPs), as an anti-fibrotic metabolic dysfunction-associated steatotic liver disease. Hepatic fibrosis is a key predictor mortality disease, driven fibrogenic hepatic stellate cells (HSCs). heart, targeting fibroblast activation protein alpha (FAP) reduce murine cardiac fibrosis. However, value approach unknown. We explored potential...
The growth of solid tumors is greatly influenced by stromal components including cancer-associated fibroblasts (CAFs) and desmoplastic matrix through both immune-dependent immune-independent mechanisms. Fibroblast activation protein (FAP) a cell target that selectively expressed at high levels on the surface CAFs. We previously established an ex vivo retroviral-transduced CAR T approach to FAP+ CAFs resulted in depletion cells, disruption matrix, enhanced immune infiltration, inhibition...
Sperm motility encompasses a wide range of events involving epididymal maturation and activation biochemical pathways, most notably cyclic AMP (cAMP)-protein kinase A (PKA) activation. Following the discovery guanine-nucleotide exchange factors (RAPGEFs), also known as proteins activated by cAMP, we investigated separate roles PKA RAPGEFs in sperm motility. RT-PCR showed presence Rapgef3, Rapgef4, Rapgef5, well several RAPGEF partner mRNAs, spermatogenic cells. However, Rapgef3 Rapgef4...
Abstract Organogenesis and regeneration require coordination of cellular proliferation, regulated in part by secreted growth factors cognate receptors, with tissue nutrient supply provided expansion patterning blood vessels. Here we reveal unexpected combinatorial integration a factor co-receptor heterodimeric partner ligand known to regulate angiogenesis vascular patterning. We show that ErbB2, which can mediate epidermal (EGF) neuregulin signalling multiple tissues, is unexpectedly...
While most ATP, the main energy source driving sperm motility, is derived from glycolysis and oxidative phosphorylation, metabolic demands of cell require efficient use power stored in high-energy phosphate bonds. In times high consumption, adenylate kinase (AK) scavenges one ATP molecule by transphosphorylation two molecules ADP, simultaneously yielding AMP as a by-product. Either or ADP supported motility detergent-modeled cauda epididymal mouse sperm, indicating that flagellar AKs are...
The Hippo signaling pathway has been implicated in control of cell and organ size, proliferation, endothelial-mesenchymal transformation. This impacts upon two partially redundant transcription cofactors, Yap Taz, that interact with other factors, including members the Tead family, to affect expression downstream genes. Taz have shown regulate, a cell-autonomous manner, myocardial hypertrophy, regenerative potential, overall size heart. Here, we show also play an instructive,...
The islets of Langerhans are endocrine organs characteristically dispersed throughout the pancreas. During development, progenitors delaminate, migrate radially and cluster to form islets. Despite distinctive distribution islets, spatially localized signals that control islet morphogenesis have not been discovered. Here, we identify a radial signaling axis instructs developing cells disperse A screen pancreatic extracellular identified factors stimulated cell development. These included...