A5020677013- Advanced Breast Cancer Therapies
- PI3K/AKT/mTOR signaling in cancer
- Cancer Mechanisms and Therapy
- Immune Cell Function and Interaction
- Single-cell and spatial transcriptomics
- Immune cells in cancer
- Protein Degradation and Inhibitors
- Melanoma and MAPK Pathways
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Arsenic contamination and mitigation
- Atherosclerosis and Cardiovascular Diseases
- IL-33, ST2, and ILC Pathways
- Chronic Lymphocytic Leukemia Research
- Mast cells and histamine
- Histone Deacetylase Inhibitors Research
- Heavy Metal Exposure and Toxicity
- T-cell and B-cell Immunology
- Cell Image Analysis Techniques
- Biomedical Research and Pathophysiology
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Ubiquitin and proteasome pathways
- Ocular Oncology and Treatments
- Cancer Cells and Metastasis
- Trace Elements in Health
Jewish General Hospital
2020-2025
McGill University
2020-2023
University of Manitoba
2023
Telesta Therapeutics (Canada)
2023
Melanomas commonly undergo a phenotype switch, from proliferative to an invasive state. Such tumor cell plasticity contributes immunotherapy resistance; however, the mechanisms are not completely understood and thus therapeutically unexploited. Using melanoma mouse models, we demonstrated that blocking MNK1/2-eIF4E axis inhibited switching sensitized anti-PD-1 immunotherapy. We showed phospho-eIF4E-deficient murine melanomas expressed high levels of melanocytic antigens, with similar results...
We investigated the role of NFE2L3 transcription factor in inflammation-induced colorectal cancer. Our studies revealed that Nfe2l3-/- mice exhibit significantly less inflammation colon, reduced tumor size and numbers, skewed localization tumors with a more pronounced decrease distal colon. CIBERSORT analysis RNA-seq data from normal tissue predicted reduction mast cells animals, which was confirmed by toluidine blue staining. Concomitantly, transcript levels Il33 Rab27a, both important...
Millions worldwide are exposed to elevated levels of arsenic that significantly increase their risk developing atherosclerosis, a pathology primarily driven by immune cells. While the impact on cell populations in atherosclerotic plaques has been broadly characterized, cellular heterogeneity is substantial barrier in-depth examinations dynamics for varying populations. This study aimed conduct single-cell multi-omics profiling apolipoprotein E knockout (ApoE-/-) mice elucidate transcriptomic...
Uveal melanoma (UM) is an eye cancer that fatal upon metastasis to the liver. Most treatments trialed in UM fail provide therapeutic benefit, thus there urgent need for novel treatment strategies. The MAPK and PI3K signaling pathways, key molecular drivers found be hyper-activated UM, converge on MNK1/2-eIF4E mTORC1/2-4EBP axes. Here, we demonstrate pharmacologic inhibition of MNK1/2 combination with mTOR inhibitor impairs clonogenic outgrowth cell invasion. Proteomic analyses reveal...
Melanomas reprogram their metabolism to rapidly adapt therapy-induced stress conditions, allowing them persist and ultimately develop resistance. We report that a subpopulation of melanoma cells tolerate MAPK pathway inhibitors (MAPKis) through concerted metabolic reprogramming mediated by peroxisomes UDP-glucose ceramide glycosyltransferase (UGCG). Compromising peroxisome biogenesis, repressing PEX3 expression, potentiated the proapoptotic effects MAPKis via an induction ceramides, effect...
The tumour microenvironment (TME) consists of tumour-supportive immune cells, endothelial and fibroblasts. PhenoCycler, a high-plex single cell spatial biology imaging platform, is used to characterize the complexity TME. Researchers worldwide harvest bank tissues from mouse models which are employed model plethora human disease. With explosion interest in biology, these panoplies archival provide valuable resource answer new questions. Here, we describe our protocols for developing tunable...
Dysregulation of the mitogen-activated protein kinase interacting kinases 1/2 (MNK1/2)–eukaryotic initiation factor 4E (eIF4E) signaling axis promotes breast cancer progression. MNK1 is known to influence stem cells (CSCs); self-renewing populations that support metastasis, recurrence, and chemotherapeutic resistance, making them a clinically relevant target. The precise function in regulating CSCs, however, remains unexplored. Here, we generated knockout cell lines, resulting diminished CSC...
Worldwide, millions of people are co-exposed to arsenic and cadmium. Environmental exposure both metals is linked with a higher risk atherosclerosis. While studies have characterized the pro-atherosclerotic effects cadmium as single agents, little known about potential metal mixtures, particularly at low doses. Here, we used combination in vitro vivo models assess low-dose individually mixtures on early events plaque development associated In vitro, investigated pro-atherogenic changes...
Aberrant cell-cycle progression is characteristic of melanoma, and CDK4/6 inhibitors, such as palbociclib, are currently being tested for efficacy in this disease. Despite the promising nature their use single agents melanoma has shown limited clinical benefit. Herein, we discovered that treatment tumor cells with palbociclib induces phosphorylation mRNA translation initiation factor eIF4E. When phosphorylated, eIF4E specifically engenders mRNAs code proteins involved cell survival. We...
Abstract Background Arsenic is a naturally occurring toxicant and industrial byproduct with significant health risks. Globally, millions of people are exposed to arsenic concentrations that exceed the World Health Organization’s recommended limit 10 μg/L. Chronic exposure linked an increased risk chronic kidney disease (CKD); however, effects on development remain unclear. Eukaryotes methylate inorganic (iAsIII) using enzyme 3 methyltransferase (As3mt), converts it methylated intermediates,...
Abstract Relapsed and refractory Diffuse Large B Cell Lymphoma (rrDLBCL) presents a significant challenge in hematology-oncology, with approximately 30-40% of DLBCL patients experiencing relapse or resistance to treatment. This underscores the urgent need better understand molecular mechanisms governing therapeutic resistance. Signal Transducer Activator Transcription 6 (STAT6) has been previously identified as gene recurrent D419 gain-of-function mutations rrDLCBL. When STAT6 are present...
Abstract Millions worldwide are exposed to elevated levels of arsenic. This significantly increases their risk developing atherosclerosis, a pathology primarily driven by immune cells. While the impact arsenic on cell populations in atherosclerotic plaques has been broadly characterized, cellular heterogeneity is substantial barrier in-depth examinations dynamics for varying populations. Here, we present one first single-cell multi-omics profiling apolipoprotein E knockout (apoE -/- ) mice...
While isolating immune cells from spleens and lungs is routinely achieved using flow cytometry, it challenging to isolate viable skin. Here, we describe a step-by-step protocol for skin digestion murine melanoma model, which amenable detection of low abundant cell populations including group 2 innate lymphoid cells.
<p>Supplementary Figure 1</p>
<p>List of differentially expressed proteins annotated by cluster with pathway analysis in BLM cells</p>
<div>Abstract<p>Aberrant cell-cycle progression is characteristic of melanoma, and CDK4/6 inhibitors, such as palbociclib, are currently being tested for efficacy in this disease. Despite the promising nature their use single agents melanoma has shown limited clinical benefit. Herein, we discovered that treatment tumor cells with palbociclib induces phosphorylation mRNA translation initiation factor eIF4E. When phosphorylated, eIF4E specifically engenders mRNAs code proteins...
<p>Supplementary Figure 3</p>
<p>Supplementary methods and Tables 1, 2, 3, 4, 6</p>
<p>Supplementary methods and Tables 1, 2, 3, 4, 6</p>
<div>Abstract<p>Aberrant cell-cycle progression is characteristic of melanoma, and CDK4/6 inhibitors, such as palbociclib, are currently being tested for efficacy in this disease. Despite the promising nature their use single agents melanoma has shown limited clinical benefit. Herein, we discovered that treatment tumor cells with palbociclib induces phosphorylation mRNA translation initiation factor eIF4E. When phosphorylated, eIF4E specifically engenders mRNAs code proteins...
<p>List of differentially expressed proteins annotated by cluster with pathway analysis in BLM cells</p>
<p>Supplementary Figure 1</p>
<p>Supplementary Figure 2</p>