A5050321521- Lung Cancer Treatments and Mutations
- Genetics, Aging, and Longevity in Model Organisms
- Lung Cancer Research Studies
- Cancer Genomics and Diagnostics
- Renal Diseases and Glomerulopathies
- Cancer Cells and Metastasis
- Circadian rhythm and melatonin
- Renal Transplantation Outcomes and Treatments
- Organ and Tissue Transplantation Research
- Cancer Research and Treatments
- Transplantation: Methods and Outcomes
- Pregnancy and Medication Impact
- Pediatric Urology and Nephrology Studies
- Organ Donation and Transplantation
- Chemical Reactions and Isotopes
- Reproductive Biology and Fertility
- Renal function and acid-base balance
- Biopolymer Synthesis and Applications
- Advanced Breast Cancer Therapies
- Polyomavirus and related diseases
- Erythrocyte Function and Pathophysiology
- Complement system in diseases
- Child and Adolescent Health
- Melanoma and MAPK Pathways
- Pregnancy and preeclampsia studies
Princess Margaret Cancer Centre
2013-2023
University Health Network
2012-2023
University of Toronto
2009-2023
Huntsman Cancer Institute
2006-2020
University of Utah
2006-2020
Health Net
2012-2019
Ontario Institute for Cancer Research
2009-2017
Great North Children's Hospital
2012-2014
Royal Victoria Infirmary
2001-2013
Boston Children's Hospital
2013
Protein-tyrosine phosphatase 1B (PTP-1B) is a major protein-tyrosine that has been implicated in the regulation of insulin action, as well other signal transduction pathways. To investigate role PTP-1B vivo, we generated homozygotic PTP-1B-null mice by targeted gene disruption. PTP-1B-deficient have remarkably low adiposity and are protected from diet-induced obesity. Decreased due to marked reduction fat cell mass without decrease adipocyte number. Leanness accompanied increased basal...
Abstract Purpose: Non–small cell lung cancer (NSCLC) is the most common cause of cancer-related deaths worldwide. There an unmet need to develop novel clinically relevant models NSCLC accelerate identification drug targets and our understanding disease. Experimental Design: Thirty surgically resected primary patient tissue 35 previously established patient-derived xenograft (PDX) were processed for organoid culture establishment. Organoids histologically molecularly characterized by cytology...
Availability of lung cancer models that closely mimic human tumors remains a significant gap in research, as tumor cell lines and mouse may not recapitulate the spectrum heterogeneity seen patients. We aimed to establish patient-derived xenograft (PDX) resource from surgically resected non-small (NSCLC). Fresh tissue surgical resection was implanted grown subcutaneous pocket non-obese severe combined immune deficient (NOD SCID) gamma mice. Subsequent passages were NOD SCID A subset matched...
Membrane anchoring of farnesylated KRAS is critical for activation RAF kinases, yet our understanding how these proteins interact on the membrane limited to isolated domains. The RAS-binding domain (RBD) and cysteine-rich (CRD) engage plasma membrane, unleashing kinase from autoinhibition. Due experimental challenges, structural insight into this tripartite KRAS:RBD-CRD:membrane complex has relied molecular dynamics simulations. Here, we report NMR studies KRAS:CRAF RBD-CRD complex. We found...
Abstract Non-small cell lung cancer (NSCLC) is the leading cause of deaths worldwide. Only a fraction NSCLC harbor actionable driver mutations and there an urgent need for patient-derived model systems that will enable development new targeted therapies. other cancers display profound proteome remodeling compared to normal tissue not predicted by DNA or RNA analyses. Here, we generate 137 xenografts (PDXs) recapitulate histology molecular features primary NSCLC. Proteome analysis PDX models...
Targeted therapies require life-long treatment, as drug discontinuation invariably leads to tumor recurrence. Recurrence is mainly driven by minor subpopulations of drug-tolerant persister (DTP) cells that survive the cytotoxic effect. In lung cancer, DTP studies have been conducted with cell line models.We an in vivo study using a adenocarcinoma patient-derived xenograft EGFR mutation. Daily treatment tumor-bearing mice for 5 6 weeks inhibitor erlotinib markedly shrunk tumors and generated...
Retinoic acid (RA) is required for normal airway epithelial cell growth and differentiation both in vivo vitro. One of the earliest events following exposure bronchial cells to RA strong induction receptor beta (RAR beta) mRNA. Previous work established that many lung cancer lines primary tumors display abnormal RAR mRNA expression, most often absence or weak expression 2 isoform, even after treatment. Restoration into beta-negative has been reported inhibit tumorigenicity. Since...
Although cancers are considered stem cell diseases, mechanisms involving alterations poorly understood. Squamous carcinoma (SQCC) is the second most common lung cancer, and its pathogenesis appears to hinge on changes in behavior of basal cells bronchial airways. Basal normally quiescent differentiate into mucociliary epithelia. Smoking triggers a hyperproliferative response resulting progressive premalignant epithelial ranging from squamous metaplasia dysplasia. These can regress naturally,...
Lung cancer is the leading cause of mortality worldwide, with squamous cell carcinoma (SQCC) being second most common form. SQCCs are thought to originate in bronchial basal cells through an injury response smoking, which results this stem population committing hyperplastic rather than mucinous and ciliated fates. Copy number gains SOX2 region 3q26–28 occur 94% SQCCs, appear act both early late disease progression by stabilizing initial promoting growth invasive carcinoma. Thus, anti-SOX2...
Carcinoma-associated fibroblasts (CAFs) are abundant stromal cells in tumor microenvironment that critically involved cancer progression. Contrasting reports have shown CAFs can either pro- or antitumorigenic roles, indicating functionally heterogeneous. Therefore, to precisely target the cancer-promoting CAF subsets, it is necessary identify specific markers define these subpopulations and understand their functions. We characterized two subsets from 28 non–small cell lung (NSCLC) patient...
Lung squamous cell carcinoma (LUSC) currently has limited therapeutic options because of the relatively few validated targets and lack clinical drugs for some these targets. Although NRF2/NFE2L2 pathway activation commonly occurs in LUSC, NRF2 predominantly been studied other cancer models. Here, we investigated function including organoid models, explored activity a small molecule inhibitor ML385, which not previously LUSC.We first role signaling LUSC line proliferation through knockdown or...
Negative regulation of receptor tyrosine kinase (RTK)/RAS signaling pathways is important for normal development and the prevention disease in humans. We have used a genetic screen C. elegans to identify genes that antagonize activity activated LET-23, member EGFR family RTKs. identified two loss-of-function mutations dpy-22,previously cloned as sop-1, promote ability LET-23 induce ectopic vulval fates. DPY-22 glutamine-rich protein most similar human TRAP230, component transcriptional...
Abstract Atypical hemolytic uremic syndrome (aHUS) is a disorder characterized by anemia, thrombocytopenia, and acute renal failure. Mutations, polymorphisms, copy number variation in complement factors inhibitors are associated with aHUS. In this study, we report the first functional non-synonymous polymorphism inhibitor C4b-binding protein (C4BP) α-chain (c.719G>A; p.Arg240His), which This heterozygous change was found 6/166 aHUS patients compared 5/542 normal (χ2 = 6.021; p 0.014),...
Apoptosis is important for normal development and removal of damaged cells. Evasion apoptosis by cancer cells one the key characteristics many tumor types. Thus, discovering agents that promote in could have great therapeutic value. Marine natural products demonstrated potential as anticancer agents, proapoptotic activity some these emerging a potentially useful property treatments. Using xenograft assay rodents, we previously found marine alkaloid naamidine A potent antitumor agent. In this...