A5007217412- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- CRISPR and Genetic Engineering
- Cancer Cells and Metastasis
- Cancer Research and Treatment
- Blood Coagulation and Thrombosis Mechanisms
- Computational Drug Discovery Methods
- Neuroendocrine Tumor Research Advances
- Virus-based gene therapy research
- PARP inhibition in cancer therapy
- Angiogenesis and VEGF in Cancer
- Pluripotent Stem Cells Research
- Lung Cancer Research Studies
- Cancer Research and Treatments
- Cell Adhesion Molecules Research
- Retinal Diseases and Treatments
- Cancer-related gene regulation
- Protease and Inhibitor Mechanisms
- RNA Research and Splicing
- MicroRNA in disease regulation
- Animal Genetics and Reproduction
- Skin and Cellular Biology Research
- Monoclonal and Polyclonal Antibodies Research
- Viral Infectious Diseases and Gene Expression in Insects
- Pancreatic function and diabetes
- Pancreatic and Hepatic Oncology Research
Sunnybrook Health Science Centre
2009-2025
Sunnybrook Research Institute
2023-2025
Sunnybrook Hospital
2023-2025
University of Toronto
2004-2024
Hochschule Düsseldorf University of Applied Sciences
2024
Kuwait Petroleum Corporation (Kuwait)
2024
École Polytechnique Fédérale de Lausanne
2016-2021
Mount Sinai Hospital
2006-2020
Lunenfeld-Tanenbaum Research Institute
2009-2020
Swiss Cancer Center Léman
2019
Efficacy of antiangiogenic immunotherapy is associated with intratumoral formation high endothelial venules.
The domesticated horse represents substantial value for the related sports and recreational fields, holds enormous potential as a model range of medical conditions commonly found in humans. Most notable these are injuries to muscles, tendons, ligaments joints. Induced pluripotent stem (iPS) cells have sparked tremendous hopes future regenerative therapies that today not possible cure. Equine iPS (EiPS) cells, addition bringing promises veterinary field, open up opportunity utilize horses...
Abstract Tissue kallikreins are members of the S1 family (clan SA) trypsin-like serine proteases and present in at least six mammalian orders. In humans, tissue (hK) encoded by 15 structurally similar, steroid hormone–regulated genes (KLK) that colocalize to chromosome 19q13.4, representing largest cluster contiguous protease entire genome. hKs widely expressed diverse tissues implicated a range normal physiologic functions from regulation blood pressure electrolyte balance remodeling,...
Desquamation of the stratum corneum is a serine protease-dependent process. Two members human tissue kallikrein (KLK) family (chymo)tryptic-like proteases, KLK5 and KLK7, are implicated in desquamation by digestion (corneo)desmosomes inhibition desquamation-related protease inhibitors (SPIs). However, epidermal localization specificity additional KLKs also supports role for these enzymes desquamation. This study aims to delineate probable contribution KLK1, KLK5, KLK6, KLK13, KLK14 examining...
Reported here is a piggyBac transposon-based expression system for the generation of doxycycline-inducible, stably transfected mammalian cell cultures large-scale protein production. The works with commonly used adherent and suspension-adapted lines requires only single transfection step. Moreover, high uniform levels observed among clones allow use stable bulk cultures, thereby eliminating time-consuming cloning steps. Under continuous doxycycline induction, have been shown to be at least 2...
Outer retinal and renal glomerular functions rely on specialized vasculature maintained by VEGF that is produced neighboring epithelial cells, the pigment epithelium (RPE) podocytes, respectively. Dysregulation of RPE- podocyte-derived associated with neovascularization in wet age-related macular degeneration (ARMD), choriocapillaris degeneration, thrombotic microangiopathy (TMA). Since complement activation genetic variants inhibitory factor H (CFH) are also features both ARMD TMA, we...
Abstract High‐grade brain cancer such as glioblastoma (GBM) remains an incurable disease. A common feature of GBM is the angiogenic vasculature, which can be targeted with selected peptides for payload delivery. We assessed ability micelle‐tagged, vascular homing RGR, CGKRK and NGR to specifically bind blood vessels in syngeneic orthotopic models. By using peptide deliver tumour necrosis factor (TNF) superfamily member LIGHT (also known TNF 14; TNFSF14) vessels, we have generated a reagent...
Human kallikrein 5 (KLK5) is a member of the human gene family serine proteases. Preliminary results indicate that protein, hK5, may be potential serological marker for breast and ovarian cancer. Other studies implicate hK5 with skin desquamation diseases. To gain further insights on physiological functions, we studied its substrate specificity, regulation activity by various inhibitors, identified candidate substrates. After producing purifying recombinant in yeast, determined k(cat)/K(m)...
Human tissue kallikreins (hKs) are a family of fifteen serine proteases. Several lines evidence suggest that hKs participate in proteolytic cascade pathways. kallikrein 5 (hK5) has trypsinlike activity, is able to self-activate, and co-expressed various tissues with other hKs. In this study, we examined the ability hK5 activate By using synthetic heptapeptides encompass activation site each recombinant pro-hKs, demonstrated pro-hK2 pro-hK3. We then showed that, following their activation,...
Netherton Syndrome (NS) is a rare and severe autosomal recessive skin disease which can be life-threatening in infants. The characterized by extensive desquamation, inflammation, allergic manifestations hair shaft defects. NS caused loss-of-function mutations SPINK5 encoding the LEKTI serine protease inhibitor. deficiency results unopposed activities of kallikrein-related peptidases (KLKs) aberrantly increased proteolysis epidermis. Spink5⁻/⁻ mice recapitulate phenotype, display enhanced...
Many autoimmune and infectious diseases are characterized by the formation of granulomas which inflammatory lesions that consist spatially organized immune cells. These sites protect host control pathogens like Mycobacterium tuberculosis (Mtb), but highly cause pathology. Using bacille Calmette-Guerin (BCG) Mtb infection in mice induce sarcoid or caseating granulomas, we show a subpopulation granuloma macrophages produces vascular endothelial growth factor (VEGF-A), recruits cells to...
Human tissue kallikrein 14 (KLK14) is a novel extracellular serine protease. Clinical data link KLK14 expression to several diseases, primarily cancer; however, little known of its (patho)-physiological role. To functionally characterize KLK14, we expressed and purified recombinant in mature proenzyme forms determined pattern, specificity, regulation, vitro substrates. By using our immunoassay, the normal and/or diseased skin, breast, prostate, ovary contained highest concentration KLK14....
Vascular networks develop from a growing vascular front that responds to VEGF and other guidance cues. Angiogenesis is required for normal tissue function, but, under conditions of stress, inappropriate vascularization can lead disease. Therefore, inhibition angiogenic sprouting may prevent neovascularization in patients with blinding neovascular eye diseases, including macular degeneration. antagonists have therapeutic benefits but also elicit off-target effects. Here, we found the Ras...
MicroRNA-mediated gene regulation has been implicated in various diseases, including cancer. This study examined the role of microRNAs (miRNAs) during tumorigenesis and malignant progression pancreatic neuroendocrine tumors (PanNETs) a genetically engineered mouse model. Previously, set miRNAs was observed to be specifically up-regulated highly invasive metastatic subtype human PanNET. Using functional assays, we now implicate different distinct phenotypes: miR-137 stimulates tumor growth...
Pancreatic neuroendocrine tumors (PanNET) comprise two molecular subtypes, relatively benign islet (IT) and invasive, metastasis-like primary (MLP) tumors. Until now, the origin of aggressive MLP has been obscure. Herein, using multi-omics approaches, we revealed that arise from IT via dedifferentiation following a reverse trajectory along developmental pathway β cells, which results in acquisition progenitor-like phenotype. Functionally, miR-181cd cluster induces IT-to-MLP transition by...
Liver-targeted gene therapy based on recombinant adeno-associated viral vectors (rAAV) shows promising therapeutic efficacy in animal models and adult-focused clinical trials. This promise, however, is not directly translatable to the growing liver, where high rates of hepatocellular proliferation are accompanied by loss episomal rAAV genomes subsequently a efficacy. We have developed hybrid rAAV/piggyBac transposon vector system combining highly efficient liver-targeting properties with...
Highlights•Activin B/ALK7 signaling acts as a barrier to tumorigenesis and metastasis•ALK7 activation by activin B induces cancer cell apoptosis•Suppression of ALK7 enables metastasis evading apoptosis•ALK7 is associated with poorer survival various cancers, including breast cancerSummaryHerein, we report that the TGFß superfamily receptor suppressor metastasis, revealed functional studies in mouse models pancreatic neuroendocrine luminal cancer, complemented experimental assays. Activation...