A5085248150- CRISPR and Genetic Engineering
- Immune Cell Function and Interaction
- SARS-CoV-2 detection and testing
- Immune cells in cancer
- Advanced biosensing and bioanalysis techniques
- Biosensors and Analytical Detection
- RNA Interference and Gene Delivery
- Tissue Engineering and Regenerative Medicine
- Liver physiology and pathology
- Mesenchymal stem cell research
- SARS-CoV-2 and COVID-19 Research
- Liver Disease Diagnosis and Treatment
- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Insect symbiosis and bacterial influences
- Pancreatic function and diabetes
- Mosquito-borne diseases and control
- Macrophage Migration Inhibitory Factor
- Chemokine receptors and signaling
- Bone Tissue Engineering Materials
- Reproductive System and Pregnancy
- Cell Adhesion Molecules Research
- Aortic aneurysm repair treatments
- Inflammatory Biomarkers in Disease Prognosis
- RNA and protein synthesis mechanisms
University Medical Center Freiburg
2025
University of California, Berkeley
2020-2024
Innovative Genomics Institute
2020-2023
QB3
2022-2023
Berkeley College
2023
University of Pittsburgh
2013-2021
McGowan Institute for Regenerative Medicine
2013-2021
UPMC Hillman Cancer Center
2017
Data Harbor (United States)
2015
Geisinger Health System
2015
CRISPR-Cas systems are host-encoded pathways that protect microbes from viral infection using an adaptive RNA-guided mechanism. Using genome-resolved metagenomics, we find CRISPR also encoded in diverse bacteriophages, where they occur as divergent and hypercompact anti-viral systems. Bacteriophage-encoded belong to all six known types, though some lack crucial components, suggesting alternate functional roles or host complementation. We describe multiple new Cas9-like proteins 44 families...
The delivery of CRISPR ribonucleoproteins (RNPs) for genome editing in vitro and vivo has important advantages over other methods, including reduced off-target immunogenic effects. However, effective RNPs remains challenging certain cell types due to low efficiency toxicity. To address these issues, we engineer self-deliverable that can promote efficient cellular uptake carry out robust without the need helper materials or biomolecules. Screening cell-penetrating peptides (CPPs) fused...
Surgical mesh devices composed of synthetic materials are commonly used for ventral hernia repair. These provide robust mechanical strength and quickly incorporated into host tissue; factors that contribute to reduced recurrence rates. However, such cause a foreign body response with the associated complications fibrosis patient discomfort. In contrast, surgical naturally occurring extracellular matrix (ECM) constructive tissue remodeling, but lack materials. A method applying porcine dermal...
The liver contains a mixture of hepatocytes with diploid or polyploid (tetraploid, octaploid, etc.) nuclear content. Polyploid are commonly found in adult mammals, representing ~90% the entire hepatic pool rodents. cellular and molecular mechanisms that regulate polyploidization have been well characterized; however, it is unclear whether function similarly multiple contexts. Answering this question has challenging because proliferating can increase decrease ploidy, animal models healthy...
Abstract DNA nanostructures are a promising tool to deliver molecular payloads cells. origami structures, where long single-stranded is folded into compact nanostructure, present an attractive approach package genes; however, effective delivery of genetic material cell nuclei has remained critical challenge. Here, we describe the use encoding intact human gene and fluorescent protein as templates for integration by CRISPR-mediated homology-directed repair (HDR). Our design includes...
Abstract CRISPR-Cas12a is an RNA-guided, programmable genome editing enzyme found within bacterial adaptive immune pathways. Unlike CRISPR-Cas9, Cas12a uses only a single catalytic site to both cleave target double-stranded DNA (dsDNA) (cis-activity) and indiscriminately degrade single-stranded (ssDNA) (trans-activity). To investigate how the relative potency of cis- versus trans-DNase activity affects Cas12a-mediated editing, we first used structure-guided engineering generate variants...
Transient delivery of CRISPR-Cas9 ribonucleoproteins (RNPs) into the central nervous system (CNS) for therapeutic genome editing could avoid limitations viral vector-based including cargo capacity, immunogenicity, and cost. Here, we tested ability cell-penetrant Cas9 RNPs to edit mouse striatum when introduced using a convection-enhanced system. These transient showed comparable neurons reduced adaptive immune responses relative one formulation delivered AAV serotype 9. The production...
Abstract Background Comprising about 40% of mucosal lymphocytes, γδ T cells represent a significant lineage in the gut, and thus are key players intestinal immune homeostasis. In contrast to αβ TCRs, TCRs able recognize antigen independent from MHC-restricted presentation. While antigens recognized by largely undefined, activation is initiated phospho-antigens members butyrophilin (BTN) family. Data both murine human studies suggest protective role pathogenesis inflammatory bowel diseases...
Abdominal aortic aneurysm (AAA), a dilatation of the infrarenal aorta, typically affects males >65 years. The pathobiological mechanisms human AAA are poorly understood. goal this study was to identify novel pathways involved in development AAAs.A custom-designed 'AAA-chip' used assay 43 differentially expressed genes identified previously published microarray between (n = 15) and control abdominal aorta. Protein analyses were performed on selected genes.Altogether 38 showed significantly...
Macrophage polarization during the host response is now a well-accepted predictor of outcomes following material implantation. Immunosenescence, dysregulation macrophage function, and delayed resolution immune responses in aged individuals have all been demonstrated, suggesting that to materials should differ from those younger individuals. However, few studies examining effects aging upon performed. The present work sought elucidate impacts polypropylene mesh implanted into 8-week-old...
Abstract The transcription factor nuclear κ B (NF- B)/p65 is the master regulator of inflammation in Duchenne muscular dystrophy (DMD). Disease severity reduced by NF- inhibition mdx mouse, a murine DMD model; however, therapeutic targeting remains problematic for patients because its fundamental role immunity. In this investigation, we found that effect blockade requires hepatocyte growth (HGF) production myogenic cells. We deleting one allele subunit p65 ( +/− ) improved survival and...
Our previous analysis using genome-wide microarray expression data revealed extreme overrepresentation of immune related genes belonging the Natural Killer (NK) Cell Mediated Cytotoxicity pathway (hsa04650) in human abdominal aortic aneurysm (AAA). We followed up studies by immunohistochemical analyses antibodies against nine members NK (VAV1, VAV3, PLCG1, PLCG2, HCST, TYROBP, PTK2B, TNFA, and GZMB) tissue samples from AAA repair operations (n = 6) control aortae 8) age-, sex-...
Abstract Hepatocellular carcinoma (HCC) patients with reduced natural killer (NK)–cell numbers and function have been shown to a poor disease outcome. Mechanisms underlying NK-cell deficiency dysfunction in HCC remain largely unresolved. α-Fetoprotein (AFP) is an oncofetal antigen produced by HCC. Previous studies demonstrated that tumor-derived AFP (tAFP) can indirectly impair activity suppressing dendritic cell function. However, direct tAFP effect on NK cells remains unexplored. The...
Regular surveillance testing of asymptomatic individuals for SARS-CoV-2 has been center to outbreak prevention on college and university campuses. Here we describe the voluntary saliva program instituted at University California, Berkeley during an early period pandemic in 2020. The was administered as a research study ahead clinical implementation, enabling us launch while continuing optimize assay. Results both protocol itself participants’ experience show how succeeded providing routine,...
Saliva is an attractive specimen type for asymptomatic surveillance of COVID-19 in large populations due to its ease collection and demonstrated utility detecting RNA from SARS-CoV-2. Multiple saliva-based viral detection protocols use a direct-to-RT-qPCR approach that eliminates nucleic acid extraction but can reduce sensitivity. To improve test sensitivity while maintaining speed, we developed robotic method SARS-CoV-2 saliva samples with high throughput. Using this assay, the Free...
Macrophage accumulation and nitrosative stress are known mechanisms underlying age-related cardiovascular pathology functional decline. The cardiac muscle microenvironment is to change with age, yet the direct effects of these changes have be studied in-depth. present study sought better elucidate role that biochemical biomechanical alterations in tissue altered phenotype functionality resident macrophages observed increasing age. To accomplish this, naïve bone marrow derived from young mice...