A5071780539- Cancer Mechanisms and Therapy
- Melanoma and MAPK Pathways
- Computational Drug Discovery Methods
- Autophagy in Disease and Therapy
- Glioma Diagnosis and Treatment
- Peripheral Nerve Disorders
- Orthopedic Surgery and Rehabilitation
- Urological Disorders and Treatments
- Nerve Injury and Rehabilitation
- Protein Degradation and Inhibitors
- Chromatin Remodeling and Cancer
- Vascular anomalies and interventions
- MicroRNA in disease regulation
- Shoulder and Clavicle Injuries
- Adipokines, Inflammation, and Metabolic Diseases
- Immune cells in cancer
- Neuroblastoma Research and Treatments
- Cancer Treatment and Pharmacology
- Urinary and Genital Oncology Studies
- Congenital Anomalies and Fetal Surgery
- Colorectal Cancer Treatments and Studies
- Respiratory viral infections research
- Cancer, Hypoxia, and Metabolism
- Ubiquitin and proteasome pathways
- Shoulder Injury and Treatment
University of Colorado Denver
2016-2024
National Jewish Health
2024
University of Colorado System
2024
University of Colorado Anschutz Medical Campus
2020-2024
University of Tulsa
2023
Children's Hospital Colorado
2017-2022
Morgan Adams Foundation
2016-2021
Texas A&M University
2016-2017
University of Denver
2017
Pitié-Salpêtrière Hospital
1996
Kinase inhibitors are effective cancer therapies, but tumors frequently develop resistance. Current strategies to circumvent resistance target the same or parallel pathways. We report here that targeting a completely different process, autophagy, can overcome multiple BRAF inhibitor mechanisms in brain tumors. BRAFV600Emutations occur many pediatric previously reported these autophagy-dependent and patient was successfully treated with autophagy chloroquine after failure of BRAFV600E...
Polarized activation of adipose tissue macrophages (ATMs) is crucial for maintaining function and mediating obesity-associated cardiovascular risk metabolic abnormalities; however, the regulatory network this key process not well defined. Here, we identified a PPARγ/microRNA-223 (miR-223) axis that controls macrophage polarization by targeting distinct downstream genes to shift cellular response various stimuli. In BM-derived macrophages, PPARγ directly enhanced miR-223 expression upon...
Abstract Adipose tissue resident B cells account for more than 20% of stromal within visceral adipose tissues; however, their functions in the niche are poorly elucidated. Here we report that miR-150 modulates function by controlling activation and interactions with other immune cells. miR-150KO mice displayed exacerbated obesity-associated inflammation systemic insulin resistance, which is recapitulated adoptive transfer cells, but not purified immunoglobulin, into obese null mice. Using...
All children experience upper respiratory tract illnesses (URI) caused by viral infections. However, some of these progress to the lower airways. Although studies have found infection with certain species are more likely trigger (LRIs), a comprehensive analysis viruses underlying early-life LRIs is lacking. Determine incidence URIs, mild and severe (mLRI, sLRI) during first 2 years life association between pathogens odds versus URIs in Puerto Rican children, population at high risk for...
Autophagy is a multistage process. Progress within the field has led to development of agents targeting both early (initiation) and late (fusion) stages this The specific stage autophagy targeted may influence cancer treatment outcomes. We have previously shown that central nervous system (CNS) tumors with BRAFV600E mutation are dependent, late-stage inhibition improves response BRAF inhibitors (BRAFi) in sensitive resistant cells. Drugs directed toward initiation been reduce tumor cell...
Epidemiologic studies demonstrate an association between early-life respiratory illnesses (RIs) and the development of childhood asthma. However, it remains uncertain whether these children are predisposed to both conditions or if RIs induce alterations in airway function, immune responses, other human biology that contribute Puerto Rican experience a disproportionate burden asthma, making them important population for investigating this complex interplay. PRIMERO,
Aberrant proinflammatory and suppressed anti-inflammatory (alternative; M2) macrophage activation underlies the chronic inflammation associated with obesity other metabolic disorders. This study demonstrates a critical role for interferon regulatory factor 6 (IRF6) in regulating M2 by suppressing peroxisome proliferator–activated receptor-γ (PPARγ) expression, regulator of alternative polarization. The data demonstrate suppression IRF6 both macrophages obese adipose tissue macrophages. Using...
Atypical teratoid/thabdoid tumor (AT/RT) remains a difficult-to-treat with 5-year overall survival rate of 15%-45%. Proteasome inhibition has recently been opened as an avenue for cancer treatment the FDA approval bortezomib (BTZ) in 2003 and carfilzomib (CFZ) 2012. The aim this study was to identify characterize pre-approved targeted therapy potential clinical trials AT/RT.We performed drug screen using panel 134 FDA-approved drugs 3 AT/RT cell lines. Follow-on vitro studies used 6 lines...
Ultrasound was used for the measurement of flow 50 dialysis fistulas. Mean 806.2 ml/min. There no difference between different types fistula. It has been observed that although vein diameter determines fistula flow, and former continues to increase even after matured, blood through does not as its velocity decreases with greater diameters. Flow measurements ultrasound have important advantages indications, which are commented.
The mitogen-activated protein kinases/extracelluar signal-regulated kinases pathway is involved in cell growth and proliferation, mutations BRAF have made it an oncogene of interest pediatric cancer. Previous studies found that as well KIAA1549-BRAF fusions are common intracranial low-grade gliomas (LGGs). Fewer tested for the presence these genetic changes spinal LGGs. aim this study was to better understand prevalence other aberrations LGG.We retrospectively analyzed 46 from patients aged...
Abstract Drilling in deepwater is very expensive, with rig rates the hundreds of thousands dollars per day and high spread costs. When coupled drilling exploration wells areas unknown "difficult" formations, risks escalate exponentially. An example this recent on ChevronTexaco Upstream Europe discovery well West Shetland province UKCS. On particular wildcat potential encountering a volcanic/basalt sequence had been highlighted at planning phase. Only limited offset data was available,...
A rare case of hydatid disease, presenting as a 12 cm. cyst in the arterial wall abdominal aorta, with progressive chronic ischemia lower limbs and repeated episodes shock is reported. The diagnostic problems, surgical procedure follow-up are presented. This first reported literature.
Abstract BACKGROUND Autophagy inhibition improves the effectiveness of RAF pathway (RAFi) and overcomes resistance mechanisms. Mechanistic links between autophagy apoptotic cell death may explain this ability. BH3 mimetics with RAFi further response. METHODS sensitive (MAF 794, AM38) resistant 794R, MAF 905-3, AM38R, B76) BRAFV600E tumor lines were analyzed at baseline, following (vemurafenib), (chloroquine or shRNAs), protein (navitoclax combination therapy. Growth assays caspase activation...
<p>Upstream regulators predicted in Ingenuity Pathway Analysis. All significant p<0.01) patient sample and cell line upstream to have changed after exposure BRAFi, organized by tab. Analysis was conducted per-patient, comparing pre- post-BRAFi RNA sequencing.</p>
<p>GSEA subgroup analysis of paired RNA samples. Subgroups were analyzed based on the presence (Enriched in post-txt mutant) or absence non-mutant) a genomic alteration at time recurrence. Subgroup was also conducted tumors with identified RTK, cell cycle, RAS-ERK alterations tumor progression.</p>
<p>Increased RTK expression and activity in AM38 resistant cells. (A) array for parental (left) (right) (B) Immunoblot of cell lysates from (P) (R) AM38. (C) Fold change RNA between parent as measured using qPCR.</p>
<p>Frequency of co-mutations in BRAF and genes interest 35,231 patients pan-cancer cohorts found cBioPortal. The bar graph represents the number with each pair alterations as dataset circles represent specific that were altered for bar. 4,865 had at least one alteration listed below.</p>
<p>Supplementary Methods</p>
<div>AbstractPurpose:<p>Selective RAF-targeted therapy is effective in some patients with BRAF<sup>V600E</sup>-mutated glioma, though emergent and adaptive resistance occurs through ill-defined mechanisms.</p>Experimental Design:<p>Paired pre-/post- RAF inhibitor (RAFi)-treated glioma samples (<i>N</i> = 15) were obtained queried for treatment-emergent genomic alterations using DNA RNA sequencing (RNA-seq). Functional validation of putative...
<p>GSEA analysis of paired RNA samples. Samples were analyzed using both the C2 (Curated Gene Sets) and C6 (Oncogenic Signature MSigDB Collections. Comparisons made either between pre- post-BRAFi samples within TGFB1-high (Group 1) (tabs Group_1_c2, Group_1_c6) or TGFB1-low 2) Group_2_c2, Group_2_c6) clusters, Group_1_vs_2_post-treatment_c2, Group_1_vs_2_post-treatment_c6). We additionally compared all without clustering All_pre_vs_post_c2, All_pre_vs_post_c6).</p>
<p>GSEA comparing paired pre-/post- treatment glioma with BRAF V600E mutations (n=10) against wild type (n = 4) specimens. Highlighted are selected groups of similar differentially expressed gene sets. WT type</p>
<p>Venn diagram detailing the gene lists used to assemble ten most commonly mutated genes in glioblastoma.</p>