A5076060000- CRISPR and Genetic Engineering
- Vector-borne infectious diseases
- Viral Infections and Vectors
- Acute Lymphoblastic Leukemia research
- Bacteriophages and microbial interactions
- Insect symbiosis and bacterial influences
- Mosquito-borne diseases and control
- Childhood Cancer Survivors' Quality of Life
- Virus-based gene therapy research
- Wnt/β-catenin signaling in development and cancer
- T-cell and Retrovirus Studies
- Biochemical and Molecular Research
- Innovation and Socioeconomic Development
- Lymphatic System and Diseases
- Vector-Borne Animal Diseases
- Mental Health Treatment and Access
- Calcium signaling and nucleotide metabolism
- Kruppel-like factors research
- Bacterial Genetics and Biotechnology
- Evolution and Genetic Dynamics
- Tissue Engineering and Regenerative Medicine
- Vascular Malformations and Hemangiomas
- Cancer-related gene regulation
- Lymphatic Disorders and Treatments
- Ophthalmology and Eye Disorders
University of California, San Francisco
2018-2024
University of Montana
2023
Universidad Católica de Santa Fe
2023
Northwestern University
2021
University of Illinois Chicago
2013-2018
Broad Center
2010
Bacterial CRISPR-Cas systems protect their host from bacteriophages and other mobile genetic elements. Mobile elements, in turn, encode various anti-CRISPR (Acr) proteins to inhibit the immune function of CRISPR-Cas. To date, Acr have been discovered for type I (subtypes I-D, I-E, I-F) II (II-A II-C) but not CRISPR systems. Here, we report discovery 12 acr genes, including inhibitors V-A I-C AcrVA1 inhibits a broad spectrum Cas12a (Cpf1) orthologs-including MbCas12a, Mb3Cas12a, AsCas12a,...
The ability to generate induced pluripotent stem (iPS) cells from a patient's somatic has provided foundation for organ regeneration without the need immune suppression. However, it not been established that differentiated progeny of iPS can effectively reverse failure vital organ. Here, we examined whether cell–derived hepatocytes have both functional and proliferative capabilities needed liver in mice with fumarylacetoacetate hydrolase deficiency. To avoid biases resulting random genomic...
Wnt/β-catenin signal transduction requires direct binding of β-catenin to Tcf/Lef proteins, an event that is classically associated with stimulating transcription by recruiting coactivators. This molecular cascade plays critical roles throughout embryonic development and normal postnatal life affecting stem cell characteristics tumor formation. Here, we show this pathway utilizes a fundamentally different mechanism regulate Tcf7l1 (formerly named Tcf3) activity. inactivates without switch...
Abstract Acute lymphoblastic leukemia (ALL) is the most common type of pediatric cancer, although about 4 every 10 cases occur in adults. The enzyme drug l-asparaginase serves as a cornerstone ALL therapy and exploits asparagine dependency cells. In addition to hydrolyzing amino acid l-asparagine, all FDA-approved l-asparaginases also have significant l-glutaminase coactivity. Since several reports suggest that l-glutamine depletion correlates with many side effects these drugs, variants...
Abstract Bacteria deploy multiple defenses to prevent mobile genetic element (MGEs) invasion. CRISPR–Cas immune systems use RNA-guided nucleases target MGEs, which counter with anti-CRISPR (Acr) proteins. Our understanding of the biology and co-evolutionary dynamics common Type I-C subtype has lagged because it lacks an in vivo phage-host model system. Here, we show anti-phage function a Pseudomonas aeruginosa system encoded on conjugative pKLC102 island, its Acr-mediated inhibition by...
Wnt/β-catenin signaling is necessary for lymphatic vascular development. Oscillatory shear stress (OSS) enhances in cultured endothelial cells (LECs) to induce expression of the lymphedema-associated transcription factors GATA2 and FOXC2. However, mechanisms by which OSS regulates FOXC2 are unknown. We show that activates autocrine LECs vitro. Tissue-specific deletion Wntless, required secretion Wnt ligands, reveals smooth muscle complementary sources ligands regulate development vivo....
Borrelia burgdorferi (Bb), the causative agent of Lyme disease, adapts to vastly different environments as it cycles between tick vector and vertebrate host. During a bloodmeal, Bb alters its gene expression prepare for infection; however, full range transcriptional changes that occur over several days inside are technically challenging capture. We developed an experimental approach enrich cells longitudinally define their global transcriptomic landscape nymphal Ixodes scapularis ticks...
: To investigate computed tomography (CT) features of exophthalmos in Chinese subjects with thyroid-associated ophthalmopathy (TAO).A total 605 eyes 325 patients due to TAO were classified as grade I (mild exophthalmos) or II (severe based on orbital CT imaging. The increased volume features, such changes from extraocular muscles, fat, both, analyzed.A analyzed, among them 62.98% presented exophthalmos, while 36.02% showed exophthalmos. In I, 56.69% fat change, and II, 89.29% exhibited...
SUMMARY Bacteria deploy multiple defense mechanisms to prevent the invasion of mobile genetic elements (MGEs). CRISPR-Cas systems use RNA-guided nucleases target MGEs, which in turn produce anti-CRISPR (Acr) proteins that inactivate Cas protein effectors. The minimal component Type I-C subtype is highly prevalent bacteria, and yet a lack tractable vivo model system has slowed its study, identification cognate Acr proteins, thus our understanding true role nature. Here, we describe MGE-MGE...
Borrelia burgdorferi ( Bb ), the causative agent of Lyme disease, must adapt to vastly different environments as bacterium cycles between tick vector and a vertebrate host. During bloodmeal, migrates from midgut salivary glands changes its gene expression, priming for infection. These tick-specific transmission events are dependent on key transcriptional regulators; however, full range that occur over several days inside technically challenging capture. We developed an experimental approach...
Borrelia burgdorferi ( Bb ), the causative agent of Lyme disease, adapts to vastly different environments as it cycles between tick vector and vertebrate host. During a bloodmeal, alters its gene expression prepare for infection; however, full range transcriptional changes that occur over several days inside are technically challenging capture. We developed an experimental approach enrich cells longitudinally define their global transcriptomic landscape nymphal Ixodes scapularis ticks during...
SUMMARY >Bacteria utilize CRISPR-Cas adaptive immune systems for protection from bacteriophages (phages), and some phages produce anti-CRISPR (Acr) proteins that inhibit function. Despite thorough mechanistic structural information Acr proteins, how they are deployed utilized by a phage during infection is unknown. Here, we show production does not guarantee replication, but instead, infections fail when population numbers fall below critical threshold. Failing can be rescued related act...
Abstract Phage-encoded anti-CRISPR (Acr) proteins inhibit CRISPR-Cas systems to allow phage replication and lysogeny maintenance. Most of the Acrs characterized date are stable stoichiometric inhibitors, while enzymatic have been biochemically, little is known about their potency, specificity, reversibility. Here, we examine AcrIF11, a widespread plasmid-encoded ADP-ribosyltransferase (ART) that inhibits Type I-F system. We present an NMR structure AcrIF11 homolog reveals chemical shift...
Wnt/β-catenin signaling is necessary for lymphatic vascular patterning and the development of valves. Oscillatory shear stress (OSS) enhances in cultured endothelial cells (LECs) to induce expression lymphedema-associated transcription factors GATA2 FOXC2. However, mechanisms by which OSS regulates FOXC2 are unknown. We show that activates autocrine LECs vitro. Tissue-specific deletion Wntless, required secretion Wnt ligands, reveals smooth muscle complimentary sources ligands regulate vivo....
<p>Supplementary methods Supplementary Text: Wolinella succinogenes as a low L-glutaminase L-asparaginase Figures: • Fig. S1. In vivo imaging showing that the L-glutaminase-diminished ErA-63Q and ErA-DM variants eliminate T-ALL LOUCY cells effectively high ErA-WT. S2: variant eliminates B-ALL SUP-B15 S3. ultra-low ErA-TM S4. vitro sensitivity of two human ALL cell lines to L-asparaginases. S5: Calibration between in flux intensity measured %huCD45+ levels peripheral blood (PB). S6....
<div>Abstract<p>Acute lymphoblastic leukemia (ALL) is the most common type of pediatric cancer, although about 4 every 10 cases occur in adults. The enzyme drug l-asparaginase serves as a cornerstone ALL therapy and exploits asparagine dependency cells. In addition to hydrolyzing amino acid l-asparagine, all FDA-approved l-asparaginases also have significant l-glutaminase coactivity. Since several reports suggest that l-glutamine depletion correlates with many side effects these...
<p>Supplementary methods Supplementary Text: Wolinella succinogenes as a low L-glutaminase L-asparaginase Figures: • Fig. S1. In vivo imaging showing that the L-glutaminase-diminished ErA-63Q and ErA-DM variants eliminate T-ALL LOUCY cells effectively high ErA-WT. S2: variant eliminates B-ALL SUP-B15 S3. ultra-low ErA-TM S4. vitro sensitivity of two human ALL cell lines to L-asparaginases. S5: Calibration between in flux intensity measured %huCD45+ levels peripheral blood (PB). S6....
<div>Abstract<p>Acute lymphoblastic leukemia (ALL) is the most common type of pediatric cancer, although about 4 every 10 cases occur in adults. The enzyme drug l-asparaginase serves as a cornerstone ALL therapy and exploits asparagine dependency cells. In addition to hydrolyzing amino acid l-asparagine, all FDA-approved l-asparaginases also have significant l-glutaminase coactivity. Since several reports suggest that l-glutamine depletion correlates with many side effects these...
Borrelia burgdorferi ( Bb ), the causative agent of Lyme disease, adapts to vastly different environments as it cycles between tick vector and vertebrate host. During a bloodmeal, alters its gene expression prepare for infection; however, full range transcriptional changes that occur over several days inside are technically challenging capture. We developed an experimental approach enrich cells longitudinally define their global transcriptomic landscape nymphal Ixodes scapularis ticks during...
ABSTRACT Borrelia burgdorferi ( Bb ), the causative agent of Lyme disease, adapts to vastly different environments as it cycles between tick vector and vertebrate host. During a bloodmeal, alters its gene expression prepare for infection; however, full range transcriptional changes that occur over several days inside are technically challenging capture. We developed an experimental approach enrich cells longitudinally define their global transcriptomic landscape nymphal Ixodes scapularis...