A5011930932- Nerve injury and regeneration
- Cancer, Stress, Anesthesia, and Immune Response
- Neurogenesis and neuroplasticity mechanisms
- Axon Guidance and Neuronal Signaling
- Neuropeptides and Animal Physiology
- Cancer-related Molecular Pathways
- Ubiquitin and proteasome pathways
- Neuroblastoma Research and Treatments
- Signaling Pathways in Disease
- Neuroinflammation and Neurodegeneration Mechanisms
- DNA Repair Mechanisms
- Autophagy in Disease and Therapy
- Nanoplatforms for cancer theranostics
- Hereditary Neurological Disorders
- Wound Healing and Treatments
- Endoplasmic Reticulum Stress and Disease
- Vagus Nerve Stimulation Research
- Cancer, Lipids, and Metabolism
- Microtubule and mitosis dynamics
- Receptor Mechanisms and Signaling
- Synthesis and Characterization of Heterocyclic Compounds
- Peroxisome Proliferator-Activated Receptors
- Mechanisms of cancer metastasis
- Protein Tyrosine Phosphatases
- Pressure Ulcer Prevention and Management
University of Saskatchewan
2020-2025
Cameco (Canada)
2020-2025
Women and Children’s Health Research Institute
2015-2024
University of Alberta
2014-2024
Lincoln University College
2024
Rajiv Gandhi Centre for Biotechnology
2007-2016
University of Calgary
2012-2015
Chromosomal instability (CIN) drives tumor heterogeneity, complicating cancer therapy. Although Polo-like kinase 1 (PLK1) overexpression induces CIN, direct inhibition of PLK1 has shown limited clinical benefits. We therefore performed a genome-wide synthetic dosage lethality (SDL) screen to identify effective alternative targets and validated over 100 candidates using in vivo vitro secondary CRISPR screens. employed direct-capture Perturb-seq assess the transcriptional consequences...
Diabetes mellitus renders both widespread and localized irreversible damage to peripheral axons while imposing critical limitations on their ability regenerate. A major failure of regenerative capacity thereby imposes a 'double hit' in diabetic patients who frequently develop focal neuropathies such as carpal tunnel syndrome addition generalized diffuse polyneuropathy. The mechanisms neuron have been speculative few approaches offered therapeutic opportunities. In this work we identify an...
Insulin offers trophic support through receptors expressed widely on peripheral neurons. In this work, we studied whether sensory neurons demonstrate resistance to its properties, a property relevant during type 2 diabetes mellitus or following supraphysiological therapy. were not only localized neuronal membranes and cytoplasm but also had unique, previously unrecognized localization nuclei. We confirmed that nanomolar doses increased neurite outgrowth of adult neurons, in response...
The intricate interactions between neurons, glial, and inflammatory cells within peripheral ganglia are physiologically important, but not well explored. Here, we show that adult dorsal root (DRG) contain populations of self-renewing cells, collectively referred as DRG resident cycling (DRCCs), active only in "quiescent" also accelerate their turnover response to distal axotomy. An unexpected proportion DRCCs were macrophages. These closely accompanied, aligned with recycling satellite glial...
The progression of prostate cancer (PC) into neuroendocrine (NEPC) is a major challenge in treating PC. In NEPC, the PC cells undergo differentiation (NED); however, exact molecular mechanism that triggers NED unknown. Peripheral nerves are recently shown to promote However, their contribution NEPC was not studied well. this study, we explored whether sympathetic neurosignaling contributes NED. We found human tumors from patients later developed metastases and castration-resistant (CRPC),...
A range of isatin-thiazolidinone hybrid analogues were synthesized and their cytotoxicity was evaluated against several cancer cell lines in vitro. The acute toxicity studies mice models revealed that these possess low systemic are safe up to 1600mg/Kg. Among the compounds synthesized, 5-(2-nitrobenzylidene)-2-(isatin-3-azino)-thiazolidin-4-one (CI) has been shown be most active, highly promising compound which induced S phase arrest cycle a time dependent manner. Our initial analysis...
Symptomatic distal sensory polyneuropathy (sDSP) is common and debilitating in people with HIV/AIDS, leading to neuropathic pain, although the condition's cause unknown. To investigate biomarkers associated pathogenic mechanisms for sDSP, we examined plasma miRNA profiles HIV/AIDS patients sDSP or without 2 independent cohorts together assessing related effects. Several miRNAs were found be increased Discovery Cohort (sDSP, n = 29; non-DSP, 40) by array analyses compared sDSP. miR-455-3p...
Telomerase reverse transcriptase (hTERT) overexpression, a hallmark of most cancers, drives tumorigenesis by enabling limitless replicative potential. Direct targeting hTERT is challenging, necessitating alternative strategies. Through genome-wide synthetic dosage lethality (SDL) screening in cancer models, including patient-derived organoids, we identify FTSJ3, an RNA 2'-O-methyltransferase, as critical vulnerability hTERT-overexpressing cells. FTSJ3 methylates telomeric repeat-containing...
Despite several decades of research, an effective therapy for peripheral nerve regeneration is still lacking. The lack knowledge molecular candidates that equally promote axon and glial cell dynamics essential poses challenges in developing therapies. Improper optimization potential therapies leading to failures ensuring their local availability nerves also additional challenges. Here, we showed the neurotrophic factor, mesencephalic astrocyte-derived factor (MANF), promotes favorable...
Perineural invasion (PNI) is the of cancer cells into nerves. Although PNI a risk factor for recurrence and metastasis, lack in vitro experimental models representing natural challenges basic studies therapeutic screening. In this work, we fully characterized dorsal root ganglia (DRG)-nerve explant model demonstrated characteristic cellular molecular features undergoing PNI. Briefly, thoracic lumbar DRGs intactly connected to nerves were co-cultured with breast prostate 3D matrix two weeks....
Background: Cisplatin (CP) is an effective chemotherapy drug for several cancers. However, the use of CP associated with peripheral neuropathy, a painful nerve disorder. Unfortunately, no therapies are available CP-induced neuropathy (CisIPN). This study explored role cytokine, macrophage migration inhibitory factor (MIF), as potential therapeutic target CisIPN. Methods: The neuroinflammation and MIF in CisIPN was evaluated mice models CisIPN, without breast cancer, after treatment...
Loss of cutaneous innervation from sensory neuropathy is included among mechanisms for impaired healing diabetic skin wounds. The relationships between axons and their local microenvironment during wound are challenged in diabetes. Here, we show that secondary closure the hairy dorsal mice delayed by diabetes associated with not only a pre-existing loss but substantial retraction around wound. At 7d following 3mm punch wound, critical period reinnervation, both intact nearby directly at...