Opportunities are being offered in the following fields with the announcements of winners in early July 2005:

Oncology
Transplantation
Obstetrics and Gynaecology
Psychiatry
Pediatric Infectious Disease-Vaccines

If you are a candidate (fellow) looking for a fellowship opportunity, please proceed as follows:

1. Review the related documents with detailed information on the program available on this website entitled:  Wyeth Pharmaceuticals & CIHR /Rx&D Research Program Fellowship Program 2005 - Request for Applications (Wyeth Fellowship Opportunities).

2. Review the research opportunities listed below and contact the supervisor/mentor in the area of interest to you directly and provide him/her with your curriculum vitae, a description of your research experience and the names of three references.  Please note that the supervisor/mentor at the site may nominate up to three (3) candidates for competitive review by the CIHR.

3. A full application to the CIHR for Scientific Peer Review must be submitted by you and the supervisor/mentor by the deadline of April 15, 2005.

Fellowship positions are available at the following sites:

Oncology 

1) Dr. Moshe Szyf, McGill University
Professor, Dept. of Pharmacology and Therapeutics
Montreal, Québec
Tel:   (514) 398-7107
Fax:   (514) 398-6690
E-mail:  moshe.szyf@pharma.mcgill.ca
Website: Dr. M. Szyf's Research Laboratory  

Metastasis is the most intractable challenge of cancer therapy.  Modal mechanisms controlling metastasis are obviously potential target for anticancer therapy.  We have recently shown that DNA hypomethylation plays a critical role in activating the gene expression program required for metastasis and that a protein originally cloned in our laboratory plays a critical role in this process.  The Post-Doc Fellow will determine the mechanism through which MBD2 acts to promote metastasis and will test the potential of MBD2 inhibitors developed in our laboratory as antimetastatic agents.

2) Dr. Raymond M. Reilly, University of Toronto
Associate Professor, Leslie Dan Faculty of Pharmacy
Toronto, Ontario
Tel:  (416) 946-5522
Fax: (416) 978-8511
E-mail:  raymond.reilly@utoronto.ca
website:  Faculty of Graduate Studies and Research, Pharmaceutical Sciences, University of Toronto  

Treatment of Multidrug-Resistant Acute Myelogenous Leukemia using the CD33 Monoclonal Antibody HuM195 Conjugated to the Subcellular Range Auger Electron-Emitter, Indium-111 (111In)

This project focuses on determining if the anti-CD33 monoclonal antibody, HuM195 conjugated to the short-range Auger electron-emitter, 111In can kill myeloid leukemia cells expressing the MDR1 multidrug resistance gene in vitro and eradicate these cells from the blood and bone marrow of engrated NOD-scid mice in vivo.  A comparison of the anti-leukemic effects of 111In-HuM195 and calicheamicin-anti CD33 immunoconjugates (CMA-676; Mylotarg®) in leukemic cells with/without MDR1 expression will be incorporated into the project.  If successful, 111In-HuM195 may provide a novel targeted approach to treating chemotherapy refractory or relapsed acute myelogenous leukemia (AML) in patients in order to prolong survival and minimize normal tissue toxicity.

Transplantation

1) Dr. Shaf Keshavjee, University of Toronto
Professor of Surgery, Director, Toronto Lung Transplant Program
Director Thoracic Surgery Research Laboratory
Toronto General Hospital
Toronto, Ontario
Tel:   (416) 340-4010
Fax:  (519) 340-4556
E-mail:  shaf.keshavjee@uhn.on.ca or s.keshavjee@utoronto.ca
Website: Shaf Keshavjee 

Inducible regression of obliterative airway fibrosis by matrix metalloproteinase inhibition: a new therapeutic strategy for obliterative bronchiolitis after lung transplantation

Obliterative bronchiolitis (OB) is fibrotic occlusion of small airways, believed to be a form of chronic rejection after lung and heart-lung transplantation.  OB occurs in more than half of long-term survivors after lung transplantation and is the most common cause of morbidity and mortality.  In spite of the significance, the etiology remains poorly understood and there is no known effective treatment.  We have focused on the importance of matrix metalloproteinases (MMPs) in our preliminary studies using an MMP inhibitor in animal models and have achieved successful regression of established fibrous occlusion of the transplanted airways.  This exciting result could potentially represent, to our knowledge, the first report of therapeutic regression of fibrotic airway occlusion.  Furthermore, the regression of fibrosis appears to be accompanied by complete regeneration of airway epithelium.  Although the number of animals is limited, this preliminary data shows encouraging potential for a novel therapeutic approach to a critical problem in lung transplantation.

2) Huifang Chen, University of Montreal
Professor of Surgery, Research Center, CHUM
Montreal, Québec
Tel:   (514) 890-8000 ext. 27081
Fax:  (514) 412-7581
E-mail: Hui.Fang.Chen@umontreal.ca
Website:  University of Montreal

Immunosuppression is currently the major approach used for the prevention and management of transplantation rejection.  Baohuoside-1 (B1), a novel flavonoid isolated from Chinese herb of Epimedium davidii with empirical structure C₂₇H₃₀O10 and a molecular weight of 514 Daltons.  The mechanism of action of B1 is not similar to that of rapamycin and FK506.  It selectively inhibits on T and B cell activation in vitro.  The immunosuppression of B1 on IL-2-activated T cell proliferation occurs in G1 to S transition.  B1 associates with expression of cyclin A and p33cdk2 proteins and production of IL-2 and its receptor.  B1 effectively prevents heart allograft rejection in rodents.  The further mechanism of action, toxicity, pharmacokinetics and efficacy of prevention allograft rejection in rodents and nonhuman primates will be investigated.

Obstetrics and Gynaecology

1) Dr. Yves Tremblay, Université Laval
Professeur titulaire, Centre de recherche du CHUQ, CHUL et Dept. de Gynécologie-Obstétrique
Québec, Québec
Tel:   (418) 656-4141, poste 46158
Fax:  (418) 654-2765
E-mail: yves.tremblay@crchul.ulaval.ca
website:  CHUL Research Center    or  The Center for Research in Biology of Reproduction (CRBR)

During gestation, lung development is modulated by steroids.  Sex is a determining factor in lung maturation with the risk of respiratory distress (RD) being higher in premature boys than in girls.  The long-term consequences of an RD episode are also higher in premature boys.  Although our understanding of the male disadvantage in RD is incomplete, a relationship has been established between the presence of androgens in the male lung and a delay in the surge of surfactant, which is the major factor in RD etiology.  Animal studies confirm these findings where administration of androgens to pregnant females delay lung maturation of female fetuses at level observed in males whereas anti-androgen accelerates lung maturation of male fetuses at level observed in females.  Using lung cell lines in culture, we showed that the lung is a very active steroidogenic tissue where synthesis occurs in PT11 and inactivation in fibroblasts.  In vivo, we showed that the androgen-synthesizing/inactivating enzyme genes are up-regulated in the developing lung in perfect timing with the surge of surfactant in both male and female fetuses.  This suggests a role for androgens in cell reprogramming.  However, their presence prior the surge of surfactant delays its development in such a way that infants born at term show normal respiratory capacity, but that premature babies are affected by RD with a prevalence for boys.  Thus, androgens play a dynamic role on lung development but according to the birth timing, their presence may be dramatic.  This project will identify, by expression profiling, androgens regulated genes in the developing lung and those expressed with sex difference with focus for their effects on the surge of surfactant.  This project is the 1st step towards developing effective interventions in humans that will facilitate acceleration of male fetal lung development - something of critical importance for affecting more positive clinical outcomes for prematurely born infants. 

2) Dr. Jacques Tremblay, Université Laval
Assistant Professeur, Dept. OBGYN
Ontogeny-Reproduction Research Unit, CHUL
Québec, Québec
Tel:   (418) 656-4141, poste 46254
Fax:  (418) 654-2765
E-mail: jacques-j.tremblay@crchul.ulaval.ca
website:  CHUL Research Center 

Endometrial cancer (EC) is the fourth most frequent cancer in women and the most frequent malignancy of the female reproductive tract.  Although the exact causes of EC are unknown, excessive estradiol appears to be the predominant risk factor.  Genes involved in steroid production, including StAR, P450scc, HSD3B2, P450c17, and P450aromatase, are aberrantly expressed in EC cells.  EC cells respond to hormonal stimuli by increasing steroidogenic gene expression leading to increased intratumoral estradiol synthesis and ultimately tumour growth.  A post-doctoral position is available to study the role of the Nur77 transcription factor, a member of the nuclear receptor superfamily, in EC cell proliferation and invasiveness.  State-of-the-art molecular and cellular biology techniques will be used to study how Nur77 regulate steroidogenic gene expression in EC cells and ultimately EC cell proliferation and invasiveness.  Research will be conducted at the CHUL Research Centre of Laval University, an internationally recognized medical research facility.

Psychiatry

1) Dr. Nicholas (Nick) John Coupland, University of Alberta
Assoc. Professor, Leader CIHR New Emerging Team in PTSD
Edmonton, Alberta
Tel:   (780) 407-3369
Fax:  (780) 407-6672
E-mail:  nc2@ualberta.ca
Website: Department of Psychiatry, University of Alberta   

The fellow will become a colleague in the CIHR Posttraumatic Stress Disorder New Emerging Team.  PTSD has been identified as a strategic research priority by the CIHR.  As part of this multi-disciplinary, translational research project, the Fellow will investigate PTSD patients for potential alterations in amino acid neurotransmitters, and biochemical neuronal and glial markers, using magnetic resonance spectroscopy; regional brain volumes, using magnetic resonance imaging; and white matter structural connections, using Diffusion Tensor Imaging.  They will gain expertise in prospective research design and in the research assessment of acute stress disorder and PTSD.

2) Dr. Raymond Lam, University of B.C.
Professor & Head, Division of Clinical Neuroscience
Director of the Mood Disorders Center at UBC Hospital
Vancouver, BC
Tel:   (604) 822-7325
Fax:  (604) 822-7922
E-mail:  r.lam@ubc.ca
website:  UBC Mood Disorders Centre

Up to 20% of people with major depressive disorder will have a chronic or treatment-resistant course of illness.  Despite the significant health burden associated with chronic depression, it is neither well studied nor treated.  This project will evaluate a novel multimodal intervention, Relief of Chronic or Resistant Depression (ReChORD), which consists of expert medication management (EMM), group-based interpersonal therapy and occupational therapy.  This pragmatic randomized controlled trial will allocate patients with chronic depression to: 1) Re-ChORD, (2) EMM alone, or (3) "treatment as usual" in the community.  A wide number of outcome measures will be examined to determine if Re-ChORD is superior to the other two treatments.  If Re-ChORD is proven effective, it can be distributed widely to improve treatment for chronic depression, to reduce the economic burden of depression by getting people back to work, and to make better use of scarce health care resources.  A fellow funded through the CIHR/Wyeth program will receive advanced training in all aspects of clinical trial methodology and, depending on individual interests, will develop expertise in clinical psychopharmacology or interpersonal psychotherapy, PhD and MD candidates will be considered for this fellowship.

3) Dr. Jean-Michel Le Mellodo, University of Alberta
Assoc. Professor, Dept. of Psychiatry
Edmonton, Alberta
Tel: (708) 407-6578
Fax:  (708) 407-6672
E-mail:  jean-michel.lemelledo@ualberta.ca
Website:  Department of Psychiatry, University of Alberta

Post Partum Depression (PPD) occurs in 10 to 15% of postpartum women.  However, women with a previous episode of PPD have more than a 25% chance of presenting with a recurrent PPD episode after a future childbirth.  Besides the feelings of inadequacy and hopelessness experienced by women with PPD, PPD impacts the baby and the mother-infant relationship.  In vivo Magnetic Resonance Spectroscopy (MRS) is the only noninvasive technique that can directly asses levels of certain neurochemicals (brain metabolites) in localized brain regions in humans.  Gamma-aminobutyric acid (GABA), glutamate (Glu), glutamine (Gln), N-acetylaspartate (NAA), creatine (Cr) and choline (Cho) are metabolites that can be measured in vivo using 1H MRS. We will prospectively investigate (in the prefrontal cortex and the dorsolateral prefrontal cortex) the fluctuations of these metabolites by performing MRS scanning from the delivery date up to 8 weeks post-delivery.  With comparison of these measurements in women who develop PPD and in women who do not, we will be able to detect the brain metabolites alterations that precede and the brain metabolite alterations that are concomitantly associated with the onset of PPD.  To the best of our knowledge this investigation will be the first MRS investigation of PPD.  This research may have a tremendous impact in the future regarding our ability to predict/prevent the occurrence of PPD and its devastating consequences.

Pediatric Infectious Disease-Vaccines

1) Dr. Patrick Provost, Université Laval
Assistant Professor, Centre de Recherche en Rhumatologie et Immunologie
Québec, Québec
Tel:   (418) 656-4141 (ext. 48842)
Fax:  (418) 654-2765
E-mail:  patrick.provost@crchul.ulaval.ca 
Website:  Patrick Provost

RNA interference (RNAi) is an endogenous, recently discovered gene regulatory process in which microRNAs (miRNAs), or exogenous small interfering RNAs (siRNAs), interfere with the translation of specific messenger RNAs.  We have shown that miRNAs/siRNAs are generated upon cleavage of double-stranded RNA structures by the ribonuclease Dicer.  Recent studies have suggested a role for RNAi in host defenses against viruses in plants.  Whether this function is conserved in mammals remains unknown.
Hepatitis C virus (HCV) infection is an increasingly serious public health concern with an estimated 170-200 million chronically infected people worldwide.  HCV is a major cause of morbidity and mortality globally; no effective anti-HCV compounds are currently available.  We demonstrated that specific structures of HCV RNA are prone to cleavage by Dicer.  In this project, the successful candidate will investigate (i) whether Dicer/RNAi potentially functions as a host defense mechanism against HCV, and (ii) whether HCV counteracts Dicer/RNAi function to escape host defenses in human cells.