A5101975098- Retinal Development and Disorders
- CRISPR and Genetic Engineering
- Ubiquitin and proteasome pathways
- Click Chemistry and Applications
- Retinal Diseases and Treatments
- Advanced Fluorescence Microscopy Techniques
- Advanced Biosensing Techniques and Applications
- Epigenetics and DNA Methylation
- Advanced biosensing and bioanalysis techniques
- Advanced Proteomics Techniques and Applications
- Genomics and Chromatin Dynamics
- Monoclonal and Polyclonal Antibodies Research
- bioluminescence and chemiluminescence research
- RNA Interference and Gene Delivery
- Biotin and Related Studies
- Advanced Materials and Mechanics
- Viral Infectious Diseases and Gene Expression in Insects
- Microfluidic and Capillary Electrophoresis Applications
- Cancer-related gene regulation
- Chemical Synthesis and Analysis
- Cancer-related Molecular Pathways
- Single-cell and spatial transcriptomics
- Photodynamic Therapy Research Studies
- Retinal and Optic Conditions
- Retinal Imaging and Analysis
University of Cologne
2023-2024
Garvan Institute of Medical Research
2020-2023
The Kinghorn Cancer Centre
2020-2022
Texas A&M University
2021-2022
Walsh University
2022
University of California, Davis
2019-2020
University of California, San Diego
2016-2018
VA San Diego Healthcare System
2018
Princeton University
2013-2017
Bayer (Germany)
2017
A previously undescribed isoelectric focusing technology allows cell signaling to be quantitatively assessed in <25 cells. High-resolution capillary isoforms and individual phosphorylation forms resolved, often baseline, a 400-nl capillary. Key the method is photochemical capture of resolved protein forms. Once immobilized, proteins can probed with specific antibodies flowed through Antibodies bound their targets are detected by chemiluminescence. Because chemiluminescent substrates...
The H3K4me3 mark in chromatin is closely correlated with actively transcribed genes, although the mechanisms involved its generation and function are not fully understood. In vitro studies recombinant purified human factors demonstrate a robust SET1 complex (SET1C)-mediated H3K4 trimethylation that dependent upon p53- p300-mediated H3 acetylation, corresponding SET1C-mediated enhancement of p300-dependent transcription reflects primary effect SET1C through trimethylation, direct SET1C-p53...
Retinal gene therapy using adeno-associated viruses (AAVs) is constrained by the mode of viral vector delivery. Intravitreal AAV injections are impeded internal limiting membrane barrier, while subretinal require invasive surgery and produce a limited region therapeutic effect. In this study, we introduce novel ocular delivery in rhesus macaques transscleral microneedles to inject AAV8 into or suprachoroidal space, potential space between choroid scleral wall eye. Using vivo imaging, found...
How cancer cells adapt to stress Bacteria harsh conditions such as antibiotic exposure by acquiring new mutations, a process called stress-induced mutagenesis. Cipponi et al. investigated whether similar programs of mutagenesis play role in the response targeted therapies. Using vitro models intense drug selection and genome-wide functional screens, authors found evidence for an analogous showed that it is regulated mammalian target rapamycin (mTOR) signaling pathway. This pathway appears...
There are currently no treatments for geographic atrophy, the advanced form of age-related macular degeneration. Hence, innovative studies needed to model this condition and prevent or delay its progression. Induced pluripotent stem cells generated from patients with atrophy healthy individuals were differentiated retinal pigment epithelium. Integrating transcriptional profiles 127,659 epithelium 43 36 controls genotype data, we identify 445 expression quantitative trait loci in cis that...
The mechanisms by which DNA alleles contribute to disease risk, drug response, and other human phenotypes are highly context-specific, varying across cell types different conditions. Human induced pluripotent stem cells uniquely suited study these context-dependent effects but lines from hundreds or thousands of individuals required. Village cultures, where multiple cultured differentiated in a single dish, provide an elegant solution for scaling experiments the necessary sample sizes...
Anchoring the protein: Proteins were immobilized rapidly under mild conditions by thiol-ene photocoupling between S-farnesyl groups attached to a genetically encodable "CAAX-box" tetrapeptide sequence (A is aliphatic) at C terminus of protein and surface-exposed thiols (see scheme). This method enables oriented covalent immobilization proteins directly from expression lysates without additional purification or derivatization steps. Detailed facts importance specialist readers are published...
Protein prenylation is a widespread post-translational modification in eukaryotes that plays crucial role membrane targeting and signal transduction. RabGTPases the largest group of post-translationally C-terminally geranylgeranylated. All Rabs are processed by Rab geranylgeranyl-transferase escort protein (REP). Human genetic defects resulting loss one two REP isoforms REP-1, lead to underprenylation manifests retinal degradation blindness known as choroideremia. In this study we used...
The site-selective modification of proteins with a functional group is an important biochemical technique, but covalent attachment desired to chosen site complicated by the reactivity other amino acid side chains, often resulting in undesired reactions. One potential solution this problem involves exploiting activity protein-modifying enzymes that recognize defined protein sequence. Protein farnesyltransferase (FTase) covalently attaches isoprenoid moiety cysteine unit context short...
To assess the transcriptomic profile of disease-specific cell populations, fibroblasts from patients with primary open-angle glaucoma (POAG) were reprogrammed into induced pluripotent stem cells (iPSCs) before being differentiated retinal organoids and compared those healthy individuals. We performed single-cell RNA sequencing a total 247,520 identified cluster-specific molecular signatures. Comparing gene expression between cases controls, we novel genetic associations for this blinding...
Frequent injections of anti-vascular endothelial growth factor (anti-VEGF) agents are a clinical burden for patients with neovascular age-related macular degeneration (AMD). Genomic disruption VEGF-A using adeno-associated viral (AAV) delivery clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 has the potential to permanently suppress aberrant angiogenesis, but factors that determine optimal efficacy unknown. Here, we investigate two widely used Cas9 endonucleases,...
Abstract Protein modification with isoprenoid lipids affects hundreds of signaling proteins in eukaryotic cells. Modification isoprenoids reporter groups is the main approach for creation probes analysis protein prenylation vitro and vivo. Here, we describe a new strategy synthesis functionalized phosphoisoprenoids that uses an aminederivatized scaffold as starting point phosphoisoprenoid libraries. This overcomes long‐standing problem field, where multistep had to be carried out each...
Cellular metabolism is the process by which cells generate energy, and many diseases, including cancer, are characterized abnormal metabolism. Reduced nicotinamide adenine (phosphate) dinucleotide (NAD(P)H) oxidized flavin (FAD) coenzymes of metabolic reactions. NAD(P)H FAD exhibit autofluorescence can be spectrally isolated excitation emission wavelengths. Both coenzymes, FAD, exist in either a free or protein-bound configuration, each has distinct fluorescence lifetime-the time for...
Stopping the transfer: Based on structure of pepticinnamin E, specific inhibitors Rab geranylgeranyl transferase (RabGGTase) with activity in cells were developed, and first crystal enzyme complex an inhibitor is reported (see positioning active site enzyme). The findings may have implications for chemical-biological study prenylation vesicular transport involvement RabGGTase establishment disease. Supporting information this article available WWW under...
Post-translational modifications (PTMs) expand the number of protein isoforms in eukaryotic proteome by orders magnitude. Protein modification with isoprenoid lipids is a common PTM affecting hundreds proteins controlling transport information and materials into, through, out cell. In this modification, soluble phosphoisoprenoid such as farnesyl (C15) or geranylgeranyl (C20) pyrophosphate moiety recruited one three prenyltransferases to covalently modify C-terminal cysteine(s) target...