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].

ENGAGE: The Role of Academic Research and Technology Innovation for Improving Parkinson’s Disease Outcome and Life-style modifications

Phase I: Development of Intellectual Property to Facilitate Partnership Agreements with Business and Non-profit

Organization

Computer Aided Spinal Cord-MRI Assessment System basedon Digital Image Processing Techniques

The spinal cord is a main pathway connecting the brain to the peripheral nervous system. Noninvasive image?based assessment of this structure is an increasingly demanding healthcare service. This project cultivates the engineering techniques required for the development of a computer?aided spinal?scan assessment software toolkit for diagnosis of spinal cord problems.

The evaluation of pain management strategies for either caustic paste or cautery disbudding in dairy calves

Destruction of the horn bud in 4-6 wk old calves using either hot-iron or chemical disbudding is a common practice in the dairy industry. There is a limited body of research on the effects of chemical disbudding and the pain it causes to the animal as well as research on appropriate methods to mitigate the pain following this procedure, and research to identify appropriate pain managements is needed.

The evaluation of pain management strategies for either caustic paste or cautery disbudding in dairy calves

Destruction of the horn bud in 4-6 wk old calves using either hot-iron or chemical disbudding is a common practice in the dairy industry. There is a limited body of research on the effects of chemical disbudding and the pain it causes to the animal as well as research on appropriate methods to mitigate the pain following this procedure, and research to identify appropriate pain managements is needed.

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