Faculty Profile

Stephen Lye

Contact Information:

Mailing Address:	Room 850 – 600 University Avenue Toronto, ON M5G 1X5
Phone Number:	416-586-8224 / 8640
Fax Number:	416-586-8857
Email Address:	lye@mshri.on.ca

Degrees & Professional Designations:
Ph.D. – Anatomy/Physiology
Associate Director Samuel Lunenfeld Research Institute

Academic Position: Professor

Primary Appointment: Obstetrics and Gynecology

Cross Appointments: Physiology; Medicine

Hospital Affiliation/Practice Location:
Vice-President – Research, Mount Sinai Hospital
Associate Director, Samuel Lunenfeld Research Institute

Key Interests:

• Preterm Birth (myometrial function, tocolysis)
• Pre-eclampsia (placental development; remodeling of uterine vasculature)
• Developmental Origins of Health and Disease (DOHaD)
• Steroid Receptor Function

Current Research Grants and Projects:
1) CIHR – Myometrial Programming: A New Concept Underlying the Control of Myometrial Contractility During Pregnancy (2005-2010): $727,080 (Principal Applicant)

2) CIHR – Paracrine Controls of Human Labour (2005-2010): $792,120 (Co-Applicant)

3) CIHR – CIHR Group n Development and Fetal Health (Group Core) (2005-2010): $1,876,250 (Co-Applicant)

4) CIHR – Regulation of Prostaglandin Synthesis, Metabolism and Action in Pregnancy and Parturition (2004-2009): $792,450 (Co-Applicant)

5) Networks of Centres of Excellence – Derivation and Primary Characterization of Human ES Cells Using Defined and Xeno-Free Conditions (2005-2008): $289,803 (Co-Applicant)

6) CIHR – SLRI Interface Training Program: Applying Genomics to Human Health (2002-2008): $1,800,000 (Co-Applicant)

7) Physicians Services Incorporated Foundation – The Diagnosis of True Pre-Term Labor (2004-2006): $159,000 (Co-Applicant)

8) March of Dimes Birth Defects Foundation – The Diagnosis of True Pre-Term Labor (2005-2008): $390,914 (Principal Applicant)

Description

Preterm Birth: We have identified that the myometrium undergoes a program of differentiation throughout pregnancy culminating in labour (proliferation – synthetic – contractile – labour). Our focus is now to determine the mechanisms that control this program with the expectation that this information will help identify approaches to control myometrial contractility during preterm labour. We are also investigating the use of meloxicam (a cyclooxygenase–2 inhibitor as a novel tocoltyic).

Pre-eclampsia: We have developed novel in vitro models to investigate the process by which trophoblast cells remodel the uterine vasculature during pregnancy. Our data suggest a key role for gap junction proteins in this process.

DOHaD: We are investigating gene-environment interactions that underlie the developmental origins of health and disease.

Steroid Receptor Function: We have identified PSF as a novel co-repressor of the progesterone and androgen receptors and are investigating the mechanisms by which it acts and its role in the regulation of pregnancy and in the pathogenesis of prostate cancer.

Recent/Key Publications:

1. Pennell, C.E., Jacobsson, B., Williams, S.M., Buus, R.M., Muglia, L.J., Dolan, S.M., Morken, N., Ozcelik, H., Lye, S.J. and Relton, C. (2006) Genetic epidemiology studies of pereterm birth – guidelines for research. Am. J. Obstet. Gynecol. (in press).

2. Gellhaus, A., Schmidt, M., Dunk, C., Lye, S.J., Kimmig, R. and Winterhager, E. (2006) Decreased expression of the angiogenic regulators CYR61 (CCN1) and NOV (CCN3) in human placenta is associated with pre-eclampsia. Mol. Hum. Reprod. 12(6):389-399.

3. Rac, V.E., Small, C., Scott, C.A., Adamson, S.L., Rurak, D., Challis, J.R. and Lye, S.J. (2006) Meloxicam effectively inhibits preterm labor uterine contractions in a chronically catheterized pregnant sheep model: Impact on fetal blood flow and fetal-maternal physiologic parameters.
Am. J. Obstet. Gynecol. (in press).

4. Döring, B., Shynlova, O., Tsui, P., Eckardt, D., Janssen-Bienhold, U., Hofmann, F., Feil, S., Feil, R., Lye, S.J. and Willecke, K. (2006) Ablation of connexin43 in uterine smooth muscle cells of the mouse causes delayed parturition. J. Cell Science 119(Pt9):1715-1722.

5. Wright, J.K., Dunk, C.E., Perkins, J.E., Winterhager, E., Kingdom, J.C.P. and Lye, S.J. (2006) EGF modulates trophoblast migration through regulation of Connexin40. Placenta 27:S114- 121.

6. Shynlova, O., Oldenhof, A., Dorogin, A., Xu, Q., Mu, J., Nashman, N. and Lye, S.J. (2006) Myometrial apoptosis: Activation of the caspase cascade in the pregnant rat myometrium at midgestation. Biology of Reproduction 74(5):839-849.

7. Dong, X., Shynlova, O., Challis, J.R.G. and Lye, S.J. (2005) Identification and characterization of the protein-associated splicing factor as a negative co-regulator of progesterone receptor. J. Biol. Chem. 280(14):13329-13340.