Regulation of T-type calcium channel activity by targeting channel trafficking – a novel approach for pain management Year two

Current therapies to manage pain either result in side effects or are insufficient and the associated medical costs and loss of work days come pose a tremendous socioeconomic burden. We recently showed that T-type channel activity is aberrantly regulated in inflammatory and neuropathic pain by the deubiquitinase USP5, and we have begun to explore this mechanism as a new therapeutic avenue based on interfering TAT peptides. We now plan to test our TATpeptides in diabetic neuropathy and inflammatory bowel pain.

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 acidsYR2

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.

Radiochemistry for the Pharmacokinetic Evaluation of Novel Bone-Targeting Peptide Hormone Derivatives

This proposed research project is about development of new bone-targeting drug called PTHPEG- BP, this new compound will overcome shortages of current clinical peptide hormone PTH, and show better treatment efficacy and lower price then the latter; several new technologies will be used on research of this PTH, such as micro Positron Emission Tomography (PET/CT), and several of its characteristics will be identified such as structure, bioactivity, and metabolism inside body.

Regulation of T-type calcium channel activity by targeting channel trafficking – a novel approach for pain management

Current therapies to manage pain either result in side effects or are insufficient and the associated medical costs and loss of work days come pose a tremendous socioeconomic burden. We recently showed that T-type channel activity is aberrantly regulated in inflammatory and neuropathic pain by the deubiquitinase USP5, and we have begun to explore this mechanism as a new therapeutic avenue based on interfering TAT peptides. We now plan to test our TATpeptides in diabetic neuropathy and inflammatory bowel pain.

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

The overall objective of this PDF project is to propose an integrated dose adaptation strategy that can be used in anticancer drug treatment. Indeed, many chemo agents used to treat tumors often induce dangerous side effects or toxicity, such as neutropenia [Crawford et al.] and hand-foot syndrome [Janusch et al.]. Since some tumors can only be destroyed by sufficiently high doses of chemotherapeutic agents, these harmful and lethal toxicities have become a main obstacle that limit the full use of the dosage of anticancer drugs or even force the discontinuation of chemo treatment.

In-plane Performance of Masonry Shear Walls

Recent research at the University of Calgary has focused on shear walls and on evaluating the influence of various parameters on in-plane shear capacity. The reason for this is that, for example, while it is recognized by most researchers that compression on walls increases the shear strength of masonry, the quantification of this effect has been reported to vary from 40 to 70% [1,8] and the factors adopted by various design standards range from 0.25 up to 0.4.

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.

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