A5048559395- CRISPR and Genetic Engineering
- Genetics, Aging, and Longevity in Model Organisms
- Neonatal Respiratory Health Research
- Infant Nutrition and Health
- Congenital Diaphragmatic Hernia Studies
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Epigenetics and DNA Methylation
- Evolution and Genetic Dynamics
- Biochemical effects in animals
- Cytomegalovirus and herpesvirus research
- RNA modifications and cancer
- Insect symbiosis and bacterial influences
- Pancreatic and Hepatic Oncology Research
- Tryptophan and brain disorders
- Hibiscus Plant Research Studies
- Animal Genetics and Reproduction
- Virus-based gene therapy research
- Genomics and Chromatin Dynamics
- Drug Transport and Resistance Mechanisms
- HIV Research and Treatment
- MicroRNA in disease regulation
- Tumors and Oncological Cases
- Blood properties and coagulation
- Innovation and Socioeconomic Development
- Cancer-related gene regulation
University of Massachusetts Chan Medical School
2014-2023
Massachusetts General Hospital
2014
Harvard University
2014
Hospital de Santa Maria
2011
Penn State Milton S. Hershey Medical Center
2011
Lankenau Institute for Medical Research
2011
Cancer Institute (WIA)
2011
Tata Memorial Hospital
2011
McCormick (United States)
2011
Washington University Medical Center
2011
Significance Preclinical studies have suggested that Hedgehog (Hh) pathway inhibition reduces growth and metastasis of pancreatic ductal adenocarcinoma (PDA), but ensuing clinical trials Hh antagonists combined with cytotoxic chemotherapy not succeeded. Here, we find in three distinct genetically engineered mouse models genetic pharmacologic activity actually accelerates PDA progression. Furthermore, the acute modulation regulates balance between epithelial stromal elements, causing...
CRISPR-based genome editing using ribonucleoprotein complexes and synthetic single-stranded oligodeoxynucleotide (ssODN) donors can be highly effective. However, reproducibility vary, precise, targeted integration of longer constructs-such as green fluorescent protein tags remains challenging in many systems. Here, we describe a streamlined optimized protocol for the nematode Caenorhabditis elegans We demonstrate its efficacy, flexibility, cost-effectiveness by affinity-tagging 14 Argonaute...
Genome editing based on CRISPR (clustered regularly interspaced short palindromic repeats)-associated nuclease (Cas9) has been successfully applied in dozens of diverse plant and animal species, including the nematode Caenorhabditis elegans. The rapid life cycle easy access to ovary by micro-injection make C. elegans an ideal organism both for applying CRISPR-Cas9 genome technology optimizing genome-editing protocols. Here we report efficient straightforward methods elegans, a Co-CRISPR...
Abstract Melting and fast cooling double stranded DNA donor molecules prior to injection dramatically increases the frequency of homology-directed repair for edits such as insertions fluorescent protein markers in Caenorhabditis elegans. Strategies described here enable consistently .....
In Caenorhabditis elegans, targeted genome editing techniques are now routinely used to generate germline edits. The remarkable ease of C. elegans is attributed the syncytial nature pachytene ovary which easily accessed by microinjection. This protocol describes step-by-step details and troubleshooting tips for entire CRISPR-Cas procedure, including gRNA design microinjection ribonucleoprotein complexes, followed screening genotyping in help accessing this powerful genetic animal system. For...
Nuclease-directed genome editing is a powerful tool for investigating physiology and has great promise as therapeutic approach to correct mutations that cause disease. In its most precise form, can use cellular homology-directed repair (HDR) pathways insert information from an exogenously supplied DNA-repair template (donor) directly into targeted genomic location. Unfortunately, particularly long insertions, toxicity delivery considerations associated with DNA limit HDR efficacy. Here, we...
Triple-negative breast cancer (TNBC) is characterized by the lack of expression estrogen receptor-α (ER-α), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2). However, pathways responsible for downregulation therapeutic receptors, as well subsequent aggressiveness, remain unknown. In this study, we discovered that lactoferrin (Lf) efficiently downregulates levels ER-α, PR, HER-2 in a proteasome-dependent manner cells, it accounts loss responsiveness to ER- or...
Intestinal microbiota play an essential role in the health of a host organism. Here, we define how commensal Escherichia coli (E. coli) alters its after long term exposure to glucose using Caenorhabditis elegans-E. system where only bacteria have direct contact with glucose. Our data reveal that bacterial processing results reduced lifespan and healthspan including locomotion, oxidative stress resistance, heat resistance C. elegans. With chronic glucose, E. exhibits growth defects increased...
Although both metastatic tumor antigen 1 (MTA1), a master chromatin modifier, and transglutaminase 2 (TG2), multifunctional enzyme, are known to be activated during inflammation, it remains unknown whether these molecules regulate inflammatory response in coordinated manner. Here we investigated the role of MTA1 regulation TG2 expression bacterial lipopolysaccharide (LPS)-stimulated mammalian cells. While studying impact status on global gene expression, unexpectedly discovered that...
Background Metastasis-associated protein 1 (MTA1), a master dual co-regulatory is found to be an integral part of NuRD (Nucleosome Remodeling and Histone Deacetylation) complex, which has indispensable transcriptional regulatory functions via histone deacetylation chromatin remodeling. Emerging literature establishes MTA1 valid DNA-damage responsive with significant role in maintaining the optimum DNA-repair activity mammalian cells exposed genotoxic stress. This function was reported...
Abstract Nuclease-directed genome editing is a powerful tool for investigating physiology and has great promise as therapeutic approach to correct mutations that cause disease. In its most precise form, can use cellular homology-directed repair (HDR) pathways insert information from an exogenously supplied DNA template (donor) directly into targeted genomic location. Unfortunately, particularly long insertions, toxicity delivery considerations associated with limit HDR efficacy. Here, we...
CRISPR-based genome-editing technologies, including nuclease editing, base and prime have recently revolutionized the development of therapeutics targeting disease-causing mutations. To advance assessment genome editing tools, a robust mouse model is valuable, particularly for evaluating
ABSTRACT CRISPR genome editing has revolutionized genetics in many organisms. In the nematode Caenorhabditis elegans one injection into each of two gonad arms an adult hermaphrodite exposes hundreds meiotic germ cells to mixtures, permitting recovery multiple indels or small precision edits from successfully injected animal. Unfortunately, particularly for long insertions, efficiencies can vary widely, necessitating injections, and often requiring co-selection strategies. Here we show that...
Abstract CRISPR-based genome editing using ribonucleoprotein (RNP) complexes and synthetic single stranded oligodeoxynucleotide (ssODN) donors can be highly effective. However, reproducibility vary, precise, targeted integration of longer constructs – such as green fluorescent protein (GFP) tags remains challenging in many systems. Here we describe a streamlined optimized protocol for the nematode C. elegans . We demonstrate its efficacy, flexibility, cost-effectiveness by affinity-tagging...
<p>PDF file - 685K</p>
<div>Abstract<p>Triple-negative breast cancer (TNBC) is characterized by the lack of expression estrogen receptor-α (ER-α), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2). However, pathways responsible for downregulation therapeutic receptors, as well subsequent aggressiveness, remain unknown. In this study, we discovered that lactoferrin (Lf) efficiently downregulates levels ER-α, PR, HER-2 in a proteasome-dependent manner cells, it accounts...
<div>Abstract<p>Triple-negative breast cancer (TNBC) is characterized by the lack of expression estrogen receptor-α (ER-α), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2). However, pathways responsible for downregulation therapeutic receptors, as well subsequent aggressiveness, remain unknown. In this study, we discovered that lactoferrin (Lf) efficiently downregulates levels ER-α, PR, HER-2 in a proteasome-dependent manner cells, it accounts...
<p>PDF file - 685K</p>
Abstract Intestinal microbiota play an essential role in the health of a host organism. Here, we define how commensal Escherichia coli (E. coli) alters its after long term exposure to glucose using C. elegans - E. system. Our data reveal that bacterial processing glucose, rather than direct ingestion by animal, results reduced lifespan and healthspan, including locomotion, oxidative stress resistance, heat resistance . Chronic produces growth defects increased advanced glycation end products...