A5020774932- CRISPR and Genetic Engineering
- Hormonal and reproductive studies
- Prostate Cancer Treatment and Research
- Orthopaedic implants and arthroplasty
- Ubiquitin and proteasome pathways
- Hippo pathway signaling and YAP/TAZ
- Bone fractures and treatments
- Nutritional Studies and Diet
- Cancer-related Molecular Pathways
- Sexual Differentiation and Disorders
- Plant Parasitism and Resistance
- Lipid metabolism and biosynthesis
- Total Knee Arthroplasty Outcomes
- Cell death mechanisms and regulation
- RNA Research and Splicing
- Molecular Biology Techniques and Applications
- Diet and metabolism studies
- RNA and protein synthesis mechanisms
- Bacterial Infections and Vaccines
- Advanced biosensing and bioanalysis techniques
- Plant and animal studies
- Protein Degradation and Inhibitors
- Plant Toxicity and Pharmacological Properties
- Genetic and Kidney Cyst Diseases
- Pulmonary Hypertension Research and Treatments
University of Arizona
2006-2022
University of Massachusetts Chan Medical School
2016-2022
Neurological Surgery
2022
University of Utah
2020
University of California, Berkeley
2020
Education University of Hong Kong
2020
University of North Carolina at Charlotte
2020
Justus-Liebig-Universität Gießen
2020
Emerald Group Publishing (United Kingdom)
2020
Leuphana University of Lüneburg
2020
CRISPR is widely used to disrupt gene function by inducing small insertions and deletions. Here, we show that some single-guide RNAs (sgRNAs) can induce exon skipping or large genomic deletions delete exons. For example, CRISPR-mediated editing of β-catenin 3, which encodes an autoinhibitory domain, induces partial the in-frame nuclear accumulation β-catenin. A single sgRNA partially alter splicing unexpected larger remove Exon adds outcomes must be accounted for, perhaps taken advantage of,...
The small GTPase KRAS is frequently mutated in human cancer and currently there are no targeted therapies for mutant tumors. Here, we show that the ubiquitin-like modifier (SUMO) pathway required KRAS-driven transformation. RNAi depletion of SUMO E2 ligase Ubc9 suppresses 3D growth colorectal cells vitro attenuates tumor vivo. In cells, a subset proteins exhibit elevated levels SUMOylation. Among these proteins, KAP1, CHD1, EIF3L collectively support anchorage-independent growth, SUMOylation...
Abstract Analysis of off-target editing is an important aspect the development safe nuclease-based genome therapeutics. in vivo assessment nuclease activity has primarily been indirect (based on discovery vitro, cells or via computational prediction) through ChIP-based detection double-strand break (DSB) DNA repair factors, which can be cumbersome. Herein we describe GUIDE-tag, enables one-step, analysis mouse liver and lung. The GUIDE-tag system utilizes tethering between Cas9 donor to...
Abstract Epichloë spp. are symbiotic fungal endophytes of many cool season grasses. The presence the often confers insect, drought and disease tolerance to host within plants does not elicit defense responses. molecular basis for this phenomenon is known. festucae , endophyte Festuca rubra expresses a salicylate hydroxylase similar NahG from bacterium Pseudomonas putida . Few enzymes have been reported. in planta expression an raised possibility that degradation plant-produced salicylic acid...
Genetic lesions that activate KRAS account for ∼30% of the 1.6 million annual cases lung cancer. Despite clinical need, is still undruggable using traditional small-molecule drugs/inhibitors. When oncogenic Kras suppressed by RNA interference, tumors initially regress but eventually recur and proliferate despite suppression Here, we show tumor cells can survive knockout Kras, indicating existence Kras-independent survival pathways. Thus, even if inhibitors were available, resistance would...
Substantial evidence indicates the importance of elevated cAMP in polycystic kidney disease (PKD). Accumulation cystic tissues may be, part, caused by enhanced adenylyl cyclase activity, but inhibition degradation phosphodiesterases (PDE) likely has an important role, because is inactivated much faster than it synthesized. PDE1 only PDE family activated Ca(2+), which reduced PKD cells. To assess contribution PDE1A subfamily to renal cyst formation, we examined expression and function...
Mutations in the Ras family of small GTPases, particularly KRAS, occur at high frequencies cancer and represent a major unmet therapeutic need due to lack effective targeted therapies. Past efforts directed inhibiting activity oncoprotein have proved difficult. We propose an alternative approach target by eliminating protein from cells with pharmacological means. In this study, we developed cell-based, high-content screening platform identify molecules that could promote degradation KRAS...
Abstract Castration-resistant prostate cancer (CRPC) has greater intratumoral testosterone concentrations than similar tumors from eugonadal men; simple diffusion does not account for this observation. This study was undertaken to ascertain the androgen uptake kinetics, functional, and clinical relevance of de novo expression steroid hormone transporter OATP1B3 (SLCO1B3). Experiments testing cellular androgens suggest that is an excellent substrate (Km = 23.2 μmol/L; Vmax 321.6...
No current clinical treatments provide an ideal long-term solution for repair of long bone segment defects. Incomplete healing prevents patients from returning to preinjury activity and ultimately requires additional surgery induce healing. Obtaining autologous graft material is costly, incurs morbidity, surgical time, quality finite. In this pilot study, 3D printed biomimetic scaffolds were used facilitate rapid bridging in critical sized defects a sheep model. An inverse trabecular pattern...
CRISPR/Cas9 has revolutionized cancer mouse models. Although loss-of-function genetics by is well-established, generating gain-of-function alleles in somatic models still challenging because of the low efficiency gene knock-in. Here we developed CRISPR-based Somatic Oncogene kNock-In for Cancer Modeling (CRISPR-SONIC), a method rapid vivo modeling using homology-independent repair to integrate oncogenes at targeted genomic locus. Using dual guide RNA strategy, integrated plasmid donor 3'-UTR...
Background and Aims Despite surgical chemotherapeutic advances, the 5‐year survival rate for stage IV hepatoblastoma (HB), predominant pediatric liver tumor, remains at 27%. Yes‐associated protein 1 (YAP1) β‐catenin co‐activation occurs in 80% of children’s HB; however, a lack conditional genetic models precludes tumor maintenance exploration. Thus, need targeted therapy unmet. Given predominance YAP1 activation HB, we sought to evaluate as therapeutic target HB. Approach Results We...
Documentation, coding, and billing for physician–patient encounters have evolved over time significant variability. Appropriate complete documentation of these can contribute to the financial viability private academic medical centers. The objectives this study were assess effect on compare authors’ institution’s distribution level compared with Medicare normative data. Four orthopedic surgery subspecialty clinics evaluated at a university outpatient clinic 1-year period. A single full-day...
The ability to transform normal human cells into cancer with the introduction of defined genetic alterations is a valuable method for understanding mechanisms oncogenesis. Easy establishment immortalized but non-transformed from various tissues would facilitate these analyses. We report here simple, one-step immortalization that involves retroviral vector mediated co-expression telomerase protein and shRNA targeting CDKN2A gene locus. demonstrate this could successfully immortalize small...
Background:There are numerous animal models available to study bone healing as well test strategies accelerate formation. Sheep commonly used for evaluation of long fractures due similar dimensions and weight bearing environments compared patients. Large critical-size defects can be created in sheep facilitate the implantable materials, osteogenic proteins, stem cell treatments. Studies have been published using plates stabilize large critical size femoral, tibial, metatarsal defects....