The fate of neutrophils and role of monocytes in sterile inflammation

Our immune system Is designed to protect us from harmful agents. It must initiate a rapid potent inflammatory response to eliminate invading pathogens. Although similar to the eradication of pathogens, the inflammatory response can also occur following a sterile injury and is required for tissue repair and wound healing. This includes trauma, ischaemia-reperfusion injury, autoimmunity or burn induced injury that occurs in the absence of any microorganisms.

Regulation of N-type calcium channel activity by Opioid receptor-like receptor - a novel mechanism to eliminate morphine tolerance

Prolonged morphine treatment is known to cause an up-regulation of ORL1 receptors in the spinal cord (12, 13), which in turn is believed to contribute to the development of morphine tolerance by altering ?-opioid receptor mediate modulation of N-type calcium channels. Indeed, ORL1 antagonists can reverse the development of tolerance, and ORL1 knockout can mediate resistance to tolerance with no changes on the acute analgesic effects of morphine (14, 15). Our lab has shown that ORL1 receptors and Cav2.2 channels form a physical signaling complex that results in tonic G??

Investigating the biophysics and structural basis for state dependent drug blockade of persistent/late sodium current (INa(P)) in the heart using photoactivatable crosslinking unnatural amino acids.

Electrical activity in the heart is controlled by the concerted activity of many proteins called ion-channels that regulate the transfer of different ions across cell membranes. Recently, researchers in biomedical science have identified that a particular component of sodium carrying ion-channel activity (called the persistent or late sodium current also known as (INa(P)) played a major role in controlling the electrical activity of the heart. More recent research suggests that this late sodium current may be involved in various cardiac diseases.

Antineoplastic evaluation of novel 3,5-bis(benzylidene)-4-piperidones

The principal objective of this proposal is to discover novel drugs to treat colon cancers. Currently colon cancer is a huge medical problem and there are many disadvantages to current drug therapies. These disadvantages include their ineffectiveness to completely eradicate cancers, causing toxic side effects and the development of multidrug resistance. A group of compounds discovered in the laboratory of the supervisor designated series 2 has significant potencies towards a number of human colon cancer cell lines.

Development of an Integral Strategy for Model-based Dose Adaptation in Chemotherapy Year Two

Drug models describe the relationship between exposure (or pharmacokinetics), response (or pharmacodynamics) for both desired and undesired effects, and individual patient characteristics. In this project, drug models will be used to propose an integrated dose adaption strategy for cancer treatment. This strategy has a particular clinical value for our partner (InVentiv Health Clinical, a Contract Research Organization) because it would allow to better inform of the drug development process, thus reducing studies´ cost, drug development duration and risks in a long run.

Development of Lipid Nanoparticle Reagents for Functional Genomics in Difficult-to-Transfect Cells In Vitro

The objective of this project is to develop lipid nanoparticle (LNP) reagents for the delivery of nucleic acids to turn off, or turn on target genes in “hard-to-transfect” neurons and stem cells in vitro and in vivo. A recent report (BCC Research, April 2011) observed that "51% of researchers employ cell-based techniques to perform transfection routinely. Although transfection techniques have been available for many years ….this procedure faces challenges such as the efficiency of gene introduction and its toxicity in cells." With an estimated market of $1.9 billion by 2016 this project will help explore high value market niche that is poised for substantial growth. It will leverage clinical grade, proprietary LNP reagents, a novel proprietary microfluidic-based manufacturing LNP technology, and a unique mechanism of action that maximizes LNP potency by combining broad expertise in technology development and commercialization from the University of British Columbia, and Precision NanoSystems Inc. (PNI).

The physiologic effects of Capsaicinoid ingestion on human metabolism and exercise performance

Additional research is required to fully understand the effects of Capsaicinoids, a supplement that contains the active ingredient in hot peppers. Previous studies have demonstrated its ability to reduce appetite and weight. However, there is lacking information regarding the effects of this supplement on cardiovascular health and exercise performance. The intern will be responsible for collecting and interpreting various physiological measurements from participants, where half will be randomly chosen to consume the supplement, while the other half will be given a placebo.

Optimization of new inhibitors of type 2 serine proteases as anti-influenza agents

The proposed project aims at optimizing new antivirals to fight influenza. Current antivirals, which target proteins of the virus, suffer from severe resistance owing to mutations in the virus. Our group has identified some enzymes in the human lung that are critical for the maturation of the influenza virus. By blocking these enzymes, we expect that the proposed treatment will be a lot less prone to the development of resistance since the target is the host and not the highly mutable virus.

Intramucosal Lorazepam spray: Whole Cell and Extracellular Eelctrophysiological Study of Pharmacokinetics and Pharmacodynamics

Epileptic patients have a long term risk of recurrent seizures and the mainstay of treatment for controlling seizures is antiepileptic drugs. Management of epileptic emergencies usually requires hospitalization and the administration of intravenous (i.v.) anticonvulsant drugs. Lorazepam i.v. is the most effective treatment of status epilepticus, and therefore is routinely used in hospital emergency departments.

Sensors Western Operational Research and Development (SWORD)

Accurate monitoring of a patient’s vital signs – including body temperature, blood pressure, and pulse oxygenation – is central to the ability of clinicians to provide appropriate medical care. In spite of this, the standard equipment used to take these measurements is inefficient, inconvenient, and expensive. Adept Diagnostics will break into the medical device market with the development of novel wireless sensor systems to track these physiological variables continuously and inobtrusively.

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