Jayachandran N Kizhakkedathu

Jayachandran N Kizhakkedathu
University of British Columbia - Vancouver | UBC · Centre for Blood Research

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262
Publications
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8,809
Citations
Citations since 2016
100 Research Items
5835 Citations
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201620172018201920202021202202004006008001,000
201620172018201920202021202202004006008001,000

Publications

Publications (262)
Article
Full-text available
3-D cell cultures are being increasingly used as in vitro models are capable of better mimicry of in vivo tissues, particularly in drug screenings where mass transfer limitations can affect the cancer biology and response to drugs. Three-dimensional microscopy techniques, such as confocal and multiphoton microscopy, have been used to elucidate data...
Article
Liver dysfunction and failure account for a major portion of premature deaths in patients suffering from various iron associated pathogeneses, particularly primary and secondary iron overload disorders, despite intensive treatment. The liver is a central player in iron homeostasis and a major iron storage organ, and currently, there are no active a...
Preprint
Full-text available
Cell-based iron overload models provide tremendous utility for the investigations into the pathogenesis of different diseases as well as assessing efficacy of various therapeutic strategies. In the literature, establishing such models vary tremendously with regards to cell lines, iron source, iron treatment conditions and duration. Due to this dive...
Article
Mussel-inspired surface chemistry based on polycatecholamines and polyphenols has been widely applied as a facile and universal method for modifying surfaces. Specifically, the catecholamine-assisted codeposition as a one-step strategy is a versatile strategy used to impart surface functionalities. Despite successful incorporation of numerous funct...
Article
Introduction: Neutrophil extracellular traps (NETs) trigger thrombin generation. We aimed to characterize the effects of DNAse on NET components (cell-free DNA [cfDNA] and histones) and thrombin generation after trauma. Methods: Citrated plasma samples were collected from trauma patients and healthy volunteers. Thrombin generation (calibrated au...
Article
Full-text available
The long-term prevention of biofilm formation on the surface of indwelling medical devices remains a challenge. Silver has been reutilized in recent years for combating biofilm formation due to its indisputable bactericidal potency; however, the toxicity, low stability, and short-term activity of the current silver coatings have limited their use....
Article
The polyanion, inorganic polyphosphate (polyP), is a procoagulant molecule which has become a promising therapeutic target in the development of antithrombotics. Neutralizing polyP's prothrombotic activity using polycationic inhibitors is one of the viable strategies to design new polyP inhibitors. However, in this approach, a fine balance between...
Article
Full-text available
Polyphosphoesters (PPEs) are a class of versatile degradable polymers. Despite the high potential of this class of polymers in biomedical applications, little is known about their blood interaction and compatibility. We evaluated the hemocompatibility of water-soluble PPEs (with different hydrophilicities and molar masses) and PPE-coated model nano...
Article
Donor organ allocation is dependent on ABO matching, restricting the opportunity for some patients to receive a life-saving transplant. The enzymes FpGalNAc deacetylase and FpGalactosaminidase, used in combination, have been described to effectively convert group A (ABO-A) red blood cells (RBCs) to group O (ABO-O). Here, we study the safety and pre...
Article
Introduction- Several in vivo studies and clinical studies have demonstrated extracellular DNA as a mediator of coagulation and this effect was reversed by the administration of DNA degrading enzyme DNase I. However, there is no clear understanding of the mechanism by which extracellular DNA activates coagulation in vitro. Conventionally, it was th...
Article
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During extracorporeal blood purification, anticoagulants are administered to prevent thrombogenesis. However, haemorrhagic complications owing to near-complete inactivation of blood coagulation and delayed recovery of haemostasis pose serious risks to patients. Here, we show in vitro and in beagle dogs that hydrogel microspheres that adsorb the coa...
Article
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Systemic immunosuppression for the mitigation of immune rejection after organ transplantation causes adverse side effects and constrains the long-term benefits of the transplanted graft. Here we show that protecting the endothelial glycocalyx in vascular allografts via the enzymatic ligation of immunosuppressive glycopolymers under cold-storage con...
Article
The current study reports the use of small amplitude oscillatory rheometry to investigate the dynamics of blood clot formation upon heparin neutralization under three different oscillatory frequencies, two of which were mimicking physiological heart rates. We utilized two different heparin antidotes, namely protamine and newly developed universal h...
Article
Host defense peptides (HDPs) have been the subject of great interest for the treatment of multidrug-resistant bacterial infections due to their multimodal activity and low induction of resistance. However, aggregation, toxicity, and short biological half-life have limited their applicability for clinical treatment. Many methods have been explored t...
Article
Exposure of blood to a foreign surface in the form of a diagnostic or therapeutic biomaterial device or implanted cells or tissues, elicits an immediate, evolutionarily conserved thrombo-inflammatory response by the host. Primarily designed to protect against invading organisms following an injury, this innate response features instantaneous activa...
Article
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Hyperbranched polyglycerol (HPG) is a biocompatible polyether polymer that is a potential colloid component in a preservation solution for suppressing interstitial edema during cold storage of a donor organ. This study evaluated the outcomes of kidney transplants after cold perfusion and storage with a HPG‐based preservation solution (HPGS) in a pi...
Article
The endothelial glycocalyx is a dynamic structure integral to blood vessel hemodynamics and capable of tightly regulating a range of biological processes (ie, innate immunity, inflammation, and coagulation) through dynamic changes in its composition of the brush structure. Evaluating the specific roles of the endothelial glycocalyx under a range of...
Article
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Site-specific proteolytic processing is an important, irreversible post-translational protein modification with implications in many diseases. Enrichment of protein N-terminal peptides followed by mass spectrometry-based identification and quantification enables proteome-wide characterization of proteolytic processes and protease substrates but is...
Article
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Quantification of iron is an important step to assess the iron burden in patients suffering from iron overload diseases, as well as tremendous value in understanding the underlying role of iron in the pathophysiology of these diseases. Current iron determination of total or labile iron, requires extensive sample handling and specialized instruments...
Article
Catheter‐associated urinary tract infections (CAUTIs) are one of the most commonly occurring hospital‐acquired infections. Current coating strategies to prevent catheter‐associated biofilm formation are limited by their poor long‐term efficiency and limited applicability to diverse materials. Here, the authors report a highly effective non‐fouling...
Article
Full-text available
Multivalent binding inhibitors are a promising new class of antivirals that prevent virus infections by inhibiting virus binding to cell membranes. The design of these inhibitors is challenging as many properties, for example, inhibitor size and functionalization with virus attachment factors, strongly influence the inhibition efficiency. Here, vir...
Article
Iron is an essential micronutrient for life. Its redox activity is a key component in a plethora of vital enzymatic reactions that take place in processes such as drug metabolism, DNA synthesis, steroid synthesis, gene regulation, and cellular respiration (oxygen transport and the electron transport chain). Bacteria are highly dependent on iron for...
Article
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Antimicrobial peptides (AMPs), otherwise known as host defence peptides (HDPs), are naturally occurring biomolecules expressed by a large array of species across the phylogenetic kingdoms. They have great potential to combat microbial infections by directly killing or inhibiting bacterial activity and/or by modulating the immune response of the hos...
Article
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Polyelectrolytes such as e.g. DNA or heparin are long linear or branched macromolecules onto which charges are appended. The counterions neutralizing these charges may dissociate in water and will largely determine the interaction of such polyelectrolytes with biomolecules and in particular with proteins. Here we review studies on the interaction o...
Article
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Nanomaterials in the blood must mitigate the immune response to have a prolonged vascular residency in vivo. The composition of the protein corona that forms at the nano-biointerface may be directing this, however, the possible correlation of corona composition with blood residency is currently unknown. Here‚ we report a panel of new soft single mo...
Preprint
Full-text available
Multivalent virus binding inhibitors are a promising new class of antivirals, preventing virus infection of cells by inhibiting the first step in the viral infection cycle - binding of viruses to the cell surface. The design of multivalent virus binding inhibitors is complex as many properties, such as inhibitor size and functionalization with viru...
Article
In this review, we highlight well-described and emerging polyanions, and the way these molecules can be targeted in the design of potential therapeutics (synthetic and biologics) with applications in thrombosis and hemostasis. It is important to strike a balance between bleeding and clotting. In thrombosis, unwanted blood clots are formed in the lu...
Article
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To our knowledge, this is the first study of the mitochondrial proteome or N-terminome during bacterial infection. Identified cleavage sites that had not been previously reported in the mitochondrial N-terminome and that were not generated in canonical apoptosis revealed a pathogen-specific strategy to control human cell apoptosis. These data infor...
Article
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Polyelektrolyte wie DNA oder Heparin sind lange lineare oder verzweigte geladene Makromoleküle. Gegenionen, die diese Ladungen neutralisieren, können im Wasser dissoziieren und bestimmen weitgehend die Wechselwirkung eines solchen Polyelektrolyten mit Biomolekülen. Dieser Artikel gibt einen Überblick über Studien zur Wechselwirkung von Proteinen mi...
Article
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The mammalian mitochondrial proteome consists of more than 1100 annotated proteins and their proteostasis is regulated by only a few ATP-dependent protease complexes. Technical advances in protein mass spectrometry allowed for detailed description of the mitoproteome from different species and tissues and their changes under specific conditions. Ho...
Article
In this highlight, we summarize the surface modification approaches for development of infection-resistant coatings for biomedical devices and implants. We discuss the relevant key and highly cited research that have been published over the last five years which report the generation of infection-resistant coatings. An important strategy utilized t...
Article
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A longstanding goal in science and engineering is to mimic the size, structure, and functionality present in biology with synthetic analogs. Today, synthetic globular polymers of several million molecular weight are unknown, and, yet, these structures are expected to exhibit unanticipated properties due to their size, compactness, and low inter-cha...
Article
With 2,129 proteins still classified by the Human Proteome Organisation (HUPO) human proteome project (HPP) as ‘missing’ without compelling evidence of protein existence (PE) in humans, we hypothesised that in-depth proteomic characterisation of tissues that are technically challenging to access and extract would yield evidence for tissue-specific...
Article
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Access to efficient enzymes that can convert A and B type red blood cells to ‘universal’ donor O would greatly increase the supply of blood for transfusions. Here we report the functional metagenomic screening of the human gut microbiome for enzymes that can remove the cognate A and B type sugar antigens. Among the genes encoded in our library of 1...
Article
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Dysregulated protease activity is often implicated in the initiation of inflammation and immune cell recruitment in gastrointestinal inflammatory diseases. Using N-terminomics/TAILS (terminal amine isotopic labeling of substrates), we compared proteases, along with their substrates and inhibitors, between colonic mucosal biopsies of healthy patient...
Article
Snakebite is a major medical concern in many parts of the world with metalloproteases playing important roles in the pathological effects of Viperidae venoms, including local tissue damage, hemorrhage and coagulopathy. Hemorrhagic Factor 3 (HF3), a metalloprotease from Bothrops jararaca venom, induces local hemorrhage and targets extracellular matr...
Article
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Background Glucose is a primary osmotic agent in peritoneal dialysis (PD) solutions, but its long-term use causes structural alteration of the peritoneal membrane (PM). Hyperbranched polyglycerol (HPG) is a promising alternative to glucose. This study was designed to compare the cellular responses of human peritoneal mesothelial cells (HPMCs) to th...
Article
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Chronic transfusion of red blood cells (RBCs) to patients with β-thalassemia, sickle cell disease, and other acquired anemic disorders generates significant amounts of bioactive iron deposits in the body. The inactivation and excretion of redox active iron(III) from the blood pool and organs are critical to prevent organ damage, and are the focus o...
Article
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MALT1 paracaspase is central for lymphocyte antigen-dependent responses including NF-κB activation. We discovered nanomolar, selective allosteric inhibitors of MALT1 that bind by displacing the side chain of Trp580, locking the protease in an inactive conformation. Interestingly, we had previously identified a patient homozygous for a MALT1 Trp580-...
Chapter
Identification of the N terminus of proteins in complex samples has been accelerated in recent years by the increased power of mass spectrometers, bioinformatic tools and biochemical methods. We developed Terminal Amine Isotopic Labeling of Substrates (TAILS), a powerful method for the isolation, identification and quantification of N terminal pept...
Article
Antimicrobial peptides have been the focus of considerable research, however issues associated with toxicity and aggregation have the potential to limit clinical applications. Here, a derivative of a truncated version of aurein 2.2 (aurein 2.2Δ3), namely peptide 73, was investigated, along with its D-amino acid counterpart (D-73) and a retro-invers...
Article
Acute kidney injury (AKI) leads to significant morbidity and mortality; unfortunately, strategies to prevent or treat AKI are lacking. In recent years, several preconditioning protocols have been shown to be effective in inducing organ protection in rodent models. Here, we characterized two of these interventions—caloric restriction and hypoxic pre...
Article
Full-text available
Bacterial attachment and biofilm formation pose major challenges to the optimal performance of indwelling devices. Current coating methods have significant deficiencies including the lack of long-term activity, easy of application and adaptability to diverse materials. Here we describe a coating method that could potentially overcome such limitatio...
Article
The human genome encodes ~20 mitochondrial proteases, yet we know little of how they sculpt the mitochondrial proteome, particularly during important mitochondrial events including apoptosis initiation. To characterize global mitochondrial proteolysis—including mitochondrial targeting sequence (MTS) removal for protein import—we refined our techniq...
Article
Cancer-associated thrombosis is managed by the administration of anticoagulants and antithrombotic agents which have a high risk of inducing hemorrhagic complications. To develop safer strategies for antithrombotic therapy, in vivo activators of the intrinsic pathway, namely cell free nucleic acids (cfNAs: DNA and RNA) have been targeted with catio...
Article
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Here we present a simple technique for re-directing reactions on the cell surface to the outermost region of the glycocalyx. Macromolecular crowding with inert polymers was utilized to reversibly alter the accessibility of glycocalyx proteoglycans toward cell-surface reactive probes allowing for reactivity control in the longitudinal direction ('z'...
Article
Full-text available
Metabolic syndrome (MetS) is commonly observed among peritoneal dialysis (PD) patients, and hyperbranched polyglycerol (HPG) is a promising glucose‐sparing osmotic agent for PD. However, the biocompatibility of a HPG‐based PD solution (HPG) in subjects with MetS has not been investigated. This study compared the local and systemic effects of a HPG...
Article
Inorganic polyphosphate (polyP) released by human platelets has recently been shown to activate blood clotting and identified as a potential target for the development of novel antithrombotics. Recent studies have shown that polymers with cationic binding groups (CBGs) inhibit polyP and attenuate thrombosis. However, a good molecular-level understa...
Article
The information regarding the nature of protein corona (and its changes) and cell binding on biomaterial surface under dynamic conditions is critical to dissect the mechanism of surface-induced thrombosis. In this manuscript, we investigated the nature of protein corona and blood cell binding in heparinized recalcified human plasma, platelet rich p...