DR. DERRICK RANCOURT

B.Sc. (Guelph), Ph.D. (Kingston) - Associate Professor, Departments of Oncology, Biochemistry & Molecular Biology and Medical Genetics

Affiliations:  Member of the Southern Alberta Cancer Research Centre and Associate Scientific Staff Member, Tom Baker Cancer Centre. Member - Southern Alberta Cancer Research Institute.

Research Interests:

Implantation Serine Proteinases

We have recently reported the expression of Implantation Serine Proteinase (ISP) genes from mouse uterus and preimplantation embryos.  The ISPs are embedded within a cluster of tryptase genes on mouse chromosome 17.  They are most closely related to members of the mast cell tryptase family, indicating that they may possess some properties characteristic of tryptases including multimerization-dependent activation. The significant similarities found in regulatory regions of ISP genes, together with the observation that ISP proteins are co-expressed and heterodimerize in the embryo and uterus suggests that they are intimately co-regulated during implantation. Inhibition of ISP proteolytic function has implicated this enzyme in the processes of embryo hatching and implantation. Accordingly, this research could potentially lead to the development of therapeutics for assisted reproduction technology (ART) and the development of non-hormonal contraceptives.

ES Cell Osteoblast and Chondrocyte Differentiation

We have developed methods for differentiating murine ESCs into osteoblasts and chondrocytes. Recently, we have been using microarray technology to identify novel pathways associated with specific differentiations. Through the identification of such pathways, novel hormones, growth factors or other agonists can be identified, which can be used to promote the efficiency of differentiation. Upon exposing differentiated EBs to various cocktails, improved yield can be detected both by fluorescence activated cell sorting or quantitative PCR. Using such approaches we have improved the efficiency of chondrogenesis from 5 to 57% and osteogenesis from 60 to 90%.  We have developed suspension culture protocols for expanding ESCs as aggregates. These aggregates are different than EBs as they are cultured in the presence of LIF and remain pleuripotent. Work is in progress to develop methods for differentiating mouse and human ESCs directly in the bioreactor, and to purify osteoblasts and chondrocytes for transplantation into animal disease models.

Recombineering

We have developed and commercialized new technologies that use bacteriophage as vectors in gene targeting and targeted mutagenesis.  We use plasmid phage recombination to direct modification cassettes to specific sites within targeting vectors.  We have developed transplacement mutagenesis, which allows the transfer of small mutations to phage targeting vectors using a cycle of integrative and excisive recombination.  We have shown that transplacement can also be used to introduce modification cassettes into gene targeting phage.  We have developed an ES cell genomic library in a gene targeting phage and have developed methods to generating targeting vectors by recombination screening.  Using embryonic stem cell gene targeting we are assisting investigators in the development of knockout mice, in order to investigate gene function in mice and to develop mouse models of human diseases.

See Derrick Rancourt WebSite

Personnel:

View Pub Med for Recent publications & abstracts

Recent Publications:

• Krawetz R, Wu E, Rancourt DE, and Matyas JM.  Osteoblasts suppress high bone turnover caused by osteolytic breast cancer in vitro. Exp Cell Res. (in press)
• Krawetz RJ, Li X, and Rancourt DE. (2009) hES caught between a ROCK inhibitor and a hard place. BioEssays 31: 336-343.
• Shah S, Smith H, Feng X, Rancourt DE, and Riabowol K. (2009) ING function in apoptosis in diverse model systems. Biochem Cell Biol. 87:117-25.
• Li X, Liu SY, Krawetz RJ, Meng G, and Rancourt DE. Serum/Feeder-Free Cryopreservation of Single Human Embryonic Stem Cells. Hum Reprod 24: 580-9.
• Yamashita A, Krawetz R, and Rancourt DE.  Loss of discordant cells during micro-mass differentiation of embryonic stem cells into the chondrocyte lineage. Cell Death Differ 16: 278-86.
• Li X, Meng G, Krawetz R, and Rancourt DE. (2008) The ROCK inhibitor Y-27632 enhances the survival rate of human embryonic stem cells following cryopreservation. Stem Cells Dev. 17: 1079-85.
• Teng GQ, Zhao X, Lees-Miller JP, Quinn FR, Li P, Rancourt DE, London B, Cross JC, and Duff HJ. (2008) The Homozygous Human Missense N629D hERG (KCNH2) Potassium Channel Mutation Causes Cardiovascular Developmental Defects and Arrhythmias in Embryonic Mice. Circulation Res. 103: 1483-91.
• Sharma N, Oikonomopoulou K, Ito K., Diamandis EP, Hollenberg MD, and Rancourt DE (2008) Substrate Specificity Determination of Mouse Implantation Serine Proteinase and Human Kallikrein 6 by Phage Display. Biol Chem 389:1097-105.
• Meng G, Liu S, Krawetz R, Chan M, Chernos J, and Rancourt DE (2008) A Novel Method for Generating Xeno-Free Human Feeder Cells for Human ES Cell Culture. Stem Cells Dev 17: 413-22.
• Woltjen K, Ito K, Tsuzuki, T and Rancourt DE. (2008) Orpheus Recombination: A Comprehensive Bacteriophage System for Murine Targeting Vector Construction by Transplacement. Meth Mol Biol 435, 79-94.
• Sharma N, Xu H, Kaur J, zur Nieden NI, Rancourt DE (2008) Characterization of Secretory Leukocyte Protease Inhibitor (SLPI) as an Inhibitor of Implantation Serine Proteinases. Mol Reprod Dev 75, 1136-42.
• Meng G, zur Nieden NI, Liu SY, Cormier JT, Kallos MS, and Rancourt DE. (2008) Properties of Murine Embryonic Stem Cells Maintained on Human Foreskin Fibroblasts without LIF. Mol Reprod Dev 75, 614-22.
• Sharma N, Xu H, Kaur J, zur Nieden NI, Rancourt DE (2008) Characterization of Secretory Leukocyte Protease Inhibitor (SLPI) as an Inhibitor of Implantation Serine Proteinases. Mol Reprod Dev 75, 1136-42.

Contact Information:

The University of Calgary
Room 300 Heritage Medical Research Building
3330 Hospital Drive NW
Calgary, Alberta Canada T2N 4N1
Phone (403) 220-2888
Fax: (403) 220-8727
E-mail:rancourt [at] ucalgary [dot] ca.