Translating knowledge about optimization of surgical recovery into achieved outcomes forpatients: A dismantling trial in colorectal surgery

This study will be a three-arm, dismantling randomized trial aimed to assess the extent to which recovery after colorectal surgery is influenced by postoperative facilitation of nutrition and mobilization. Adult patients (> 18 years) with colonic or rectal diseases planned for colorectal resection at the Montreal General Hospital will be considered for inclusion. Criteria for exclusion will be: metastatic disease, medical conditions that preclude adequate postoperative feeding and/or mobilization (e.g.

Developmental potential of oocytes after cryopreservation

Overall aim of the project: To establish the protocol for oocyte cryopreservation which results in a high success rate of embryo development. We will first use mouse oocytes to test the effects of various compounds supplemented in the cryopreservation medium on subsequent oocyte competence. The mouse has been useful model for elucidating various aspects of oogenesis and reproductive development events including, global oocyte gene expression, intra-oocyte redox state, and critical events during meiotic initiation in the ovary, follicle formation and oocyte growth and maturation.

Assessment and selection of competent oocytes for embryo development

Research project aims:

1) To capture and compare microRNA (MIR) signatures in mouse ovarian follicular fluid and spent media of cumulous cells-oocyte complexes (COCs) isolated from infertility mouse models to identify one or more unique MIR signatures that will distinguish competent oocytes from incompetent oocytes.

Development of therapeutic peptides to treat bacterial and viral infections

Peptide therapeutics are a novel approach to treat bacterial and viral infections, which have major advantages over small molecules. Peptide molecules have been used previously to treat HIV infections, and I have previously shown that peptide molecules targeting Chlamydia can prevent infection in vivo. Project Objectives: 1. To take previously characterized peptides, move them onto an HSA scaffold, and evaluate their expression in a yeast system. 2. To test the HSA scaffold therapeutic peptides in vitro against Chlamydia infection, RSV infection, and influenza infection. 3.

Design and Synthesis of Specific Inhibitors of CYP26 for Blocking Retinoic Acid Metabolism: A Safer Approach to Retinoid Therapy for Skin Disease

OBJECTIVE; We will advance our development of novel specific inhibitors of the retinoic acid (RA) metabolizing P450 enzymes, CYP26A1 and CYP26B1, to treat skin disorders - an approach that will have significant safety advantages over current retinoid therapies. These inhibitors will be used primarily to target cystic acne but will also be evaluated for their therapeutic potential in treating other skin disorders including actinic keratosis, rosacea, oral leukoplakia and skin cancer.

Indanio Fellowship

My objectives will be 1) to establish stable zebrafish lines expressing the human nuclear receptors not yet established by Indanio; 2) to de-orphanize at least three human nuclear receptors; 3) to lead initiatives in drug target identification and validation; and 4) to establish protocols for structural and pharmacokinetic analysis of potential drug targets. 1) Establishing the zebrafish lines will be accomplished using the Indanio-designed reporter system and standard molecular biology techniques. 2) The strategy to adopt orphaned nuclear receptors is a multistage project.

Development and Evaluation of a Life Threatening Illness Point-of-Care Triage Test for the Fionet System

Building on our previous research and POC test prototype development, our goals for the project are to: 1) to confirm and further validate the association of altered levels of endothelial biomarkers with disease severity and mortality outcomes from LTIs in large patient populations in two settings, and 2) develop a rapid POC triage test for their detection at the bedside.

Tumor Reduction and Enhanced Responsiveness to Radiation Therapy and Chemotherapy Via Selective Removal of Iron: Mechanism and Preclinical Evaluation

Objectives: The objectives of this study are to use in vitro and in vivo models to validate the hypothesis that the ironchelator, DIBI, can selectively inhibit the proliferation and survival of breast cancer cells and that the combination of this chelator with radiation or standard chemotherapeutic agents (e.g., cisplatin and docetaxel) increases the sensitivity of breast cancer cells to the treatment regime. In collaboration with Chelation Partners Inc.

Development of 3D culture reagents and scoring systems for assays of normal andmalignant epithelial stem cells

The overarching objective of this proposal is to develop and validate a new, robust and reproducible 3D culture system that supports the clonal growth of primary sources of normal and malignant human epithelial cells and that is suitable for commercialization by STEMCELL Technologies who will partner in its development. The work will systematically address 3 Specific Aims.

Predictive microsimulation model for knee-OA progression and cost-effectiveness of earlynon-pharmacological therapies to improve long term patient outcomes

The proposed study has three objectives:

Objective 1. Develop KOA microsimulation model: To develop and validate a Knee-OA population-based microsimulation model (POHEM-KOA) using the previously developed POHEM-OA model.

Objective 2. Perform cost-effectiveness analysis of non-pharmacological therapies for KOA: To use POHEM-KOA in conducting a cost-effectiveness analysis of treatment strategies, including exercise therapy and weight reduction, targeted at obese and overweight early OA patients in Canada over the next 20 years [2013, 2033].

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