- Signaling Pathways in Disease
- Biochemical and Molecular Research
- Endoplasmic Reticulum Stress and Disease
- NF-κB Signaling Pathways
- Cell death mechanisms and regulation
- Histone Deacetylase Inhibitors Research
- Ubiquitin and proteasome pathways
- Cytokine Signaling Pathways and Interactions
- Peptidase Inhibition and Analysis
- Mitochondrial Function and Pathology
- Inflammatory mediators and NSAID effects
- Protein Tyrosine Phosphatases
- Cancer Immunotherapy and Biomarkers
- Hippo pathway signaling and YAP/TAZ
- Colorectal Cancer Treatments and Studies
- Immunodeficiency and Autoimmune Disorders
- Protease and Inhibitor Mechanisms
- HER2/EGFR in Cancer Research
- Cancer, Stress, Anesthesia, and Immune Response
- Calpain Protease Function and Regulation
- Adenosine and Purinergic Signaling
- Healthcare and Environmental Waste Management
- PARP inhibition in cancer therapy
- ATP Synthase and ATPases Research
- Ion channel regulation and function
Women and Children’s Health Research Institute
2016-2019
University of Alberta
1991-2019
University of Manitoba
2018
Universidad Nacional Autónoma de México
2018
Beth Israel Deaconess Hospital
2003-2005
Harvard University
2002-2005
Dana-Farber Cancer Institute
2000-2001
Pediatric Oncology Group
2000
University of Toronto
1991
The distribution of calsequestrin and calreticulin in smooth muscle non-muscle tissues was investigated. Immunoblots endoplasmic reticulum proteins probed with anti-calreticulin anti-calsequestrin antibodies revealed that only is present the rat liver reticulum. Membrane fractions isolated from uterine muscle, which are enriched sarcoplasmic reticulum, contain a protein band immunoreactive but not antibodies. presence these membrane further confirmed by 45Ca2+ overlay Stains-All techniques....
We report here that calreticulin interacts with protein disulfide isomerase (PDI). The PDI-calreticulin complex can be dissociated by Zn2+-iminodiacetate-substituted Sepharose-agarose chromatography, suggesting these interactions may Zn2+ dependent. Direct interaction between and PDI is also documented affinity chromatography. was the only pancreatic microsomal retained on column. Calreticulin were identified their NH2-terminal amino acid sequence analysis, mobilities in SDS-polyacrylamide...
Phosphatidylinositol 3'-kinase (PI3K) is a key component of multiple signaling pathways, where it typically promotes survival, proliferation, and/or adhesion. Here, we show that in TCR signaling, the scaffolding adapter Gab2 delivers an inhibitory signal via PI3K. Overexpression T cell lines inhibits TCR-evoked activation IL-2 promoter, blocking NF-AT- and NF-kappaB-directed transcription. Inhibition abrogated by mutating p85-binding sites, treatment with PI3K inhibitors or cotransfection...
Fas apoptotic signaling regulates diverse physiological processes. Acute activation of triggers massive apoptosis in liver. Upon receptor stimulation, the BH3-only protein Bid is cleaved into active form, tBid. Subsequent tBid recruitment to mitochondria, which facilitated by its MTCH2 at outer mitochondrial membrane (OMM), a critical step for commitment via effector proteins Bax or Bak. MOAP-1 Bax-binding enriched OMM. Here, we show that MOAP-1-deficient mice are resistant Fas-induced...
The Bcl-2-associated death promoter BAD is a prognostic indicator for good clinical outcome of breast cancer patients; however, whether affects biology unknown. Here we showed that increased cell growth in cells through two distinct mechanisms. Phosphorylation at S118 S99 phosphorylation, 14-3-3 binding and AKT activation to promote survival. Through second, more prominent pathway, stimulated mitochondrial oxygen consumption novel manner was downstream substrate entry into the mitochondria....
Receptor-interacting protein kinase 2 (RIP2 or RICK, herein referred to as RIPK2) is linked the pathogen pathway that activates nuclear factor <i>κ</i>-light-chain-enhancer of activated B cells (NF<i>κ</i>B) and autophagic activation. Using molecular modeling (docking) chemoinformatics analyses, we used RIPK2/ponatinib crystal structure searched in chemical databases for small molecules exerting binding interactions similar those exerted by ponatinib. The identified RIPK2 inhibitors potently...
Background: Multiple animal antigens, spores and pollens were collected identified from the Kuwaiti atmosphere.The role for these antigens in mediating allergic rhinitis residents needs to be evaluated.Objective: To investigate causes (both indoors outdoors) of residents.Method: This is a retrospective study all positive skin tests that we obtained our Allergy clinic Mubarak Alkabeer Hospital Kuwait, during period between May 2013 December 2015, patients who presented with symptoms and/or...
We describe an extractionless real-time reverse transcriptase-PCR (rRT-PCR) protocol for SARS-CoV-2 nucleic acid detection using heat as accurate cost-effective high-capacity solution to COVID-19 testing. present the effect of temperature, transport media, rRT-PCR mastermixes and gene assays on amplification limits detection. Utilizing our heated methodology, were 12.5 1 genome copy/reaction singleplex E- N1-gene assays, respectively, by utilizing E/N1 or Orf1ab/N1 multiplex assay...
Interleukin-3 (IL-3) regulates cell growth by affecting various processes such as death, survival, and proliferation. Cues from the external environment are sensed surface receptors, complex signaling mechanisms arise within cells, leading to specific functional outcomes. In this study, we demonstrate that cytokine IL-3 induces activation of Ca(2+)-dependent phosphatase, calcineurin (Cn). Furthermore Cn dephosphorylates Gab2, resulting in c-fos We also report there is a direct interaction...
Introduction. Metabolic dysfunction and chronic inflammation are robust molecular drivers of many diseases such as obesity, diabetes inflammatory bowel disease (IBD). Indeed, since is essentially a necessary component tissue repair, it stands to reason that energy for key repair mechanisms function properly. The underlying driving IBD currently attributed broad spectrum susceptible genes modulates the appearance, maintenance progression IBD. Precision medicine relies on defining patient...
Tkaczuk, Jean1; Milford, Edgar L.2; Carpenter, Charles B.2; Yu, Chao-Lan1; Baksh, Shairaz1; Burakoff, Steven J.1; McKay, Dianne B.1,2 Author Information
The tumor suppressor protein RASSF1A is epigenetically silenced in 40-50% of breast, prostate and ovarian cancers, making it an important player reproductive cancers. promotes apoptotic response following the binding necrosis factor alpha (TNFá) to receptor 1 (TNF-R1) on surface a cell. In contrast, non-catalytic adapter Grb2 binds constitutively TNF-R1, enhanced expression has been observed breast cancer cells. This suggests that there may be antagonism between leading death versus...
Persistent inflammation can trigger altered epigenetic, inflammatory and bioenergetics states. Inflammatory bowel disease (IBD) is a heterogeneous with an abnormal state subsequent metabolic syndrome disorder leptin alterations in the kinase, AMP-activated protein kinase (AMPK). Altered IBD has been well studied > 90% of current therapeutics are directed to inhibiting elements that drive epithelial cells colonic crypt. We hypothesize completely resolve mucosal we must (i) Inhibit mediators...