David Olson

Biography

Research Focus Despite enormous efforts, preterm birth (<37 weeks of gestation) remains the leading cause of morbidity and mortality in babies. Our laboratory studies the various genetic, physiological and environmental factors that contribute to both term and preterm labour. Our long-term objective is to translate basic science discoveries to practical prognostic and therapeutic applications to improve the health of mothers and babies.  Research Projects The prostaglandin F receptor (PTGFR) and birth  We are defining the regulation and role of the prostaglandin (PG)F2a receptor (FP) in the control of parturition at term and preterm. Single nucleotide polymorphisms and stress in the etiology of spontaneous preterm birth Currently, the majority of preterm deliveries are still unexplained. Pregnancy and parturition involve complex pathways in both mother and fetus, some of which may be termed environmental. These include stress, inflammation, hemorrhage and pathologic uterine distension. Most commonly. they are present in various degrees of combination. In addition to these environmental factors, there is also a strong genetic basis for preterm birth.  In new studies, we are exploring gene-environment interactions and seeking a transcriptomic predictor of preterm birth. With an international group of scientists led by PreHOT member, Craig Pennell (University of Western Australia), and sponsored by PreHOT, the World Health Organization and the March of Dimes, we just recently announced a SNP signature that is highly associated with Caucasian women who delivered preterm at < 34 weeks of gestation. We have confirmed that this signature is robust, i.e. it is replicated (p<1x10^-8) in similar cohorts of women around the world, including our Edmonton cohort. We have filed a provisional patent for the signature. The prognostic test we will develop to predict risk for women of preterm delivery can be taken by non-pregnant women.  Studies on mechanisms of uterine activation for labour: interactions between corticotropin-releasing hormone and prostaglandins During most of pregnancy, the myometrium remains in a relatively quiescent state until it is activated to initiate the contractions required for labour and delivery of the baby.  Although the mechanisms that control the transition of the myometrium from a quiescent to an active state remain unknown, increasing lines of evidence suggest the local stimulators, corticotropin-releasing hormone (CRH) and prostaglandins (PGs), may have a synergistic relationship of mutual amplification that leads to uterine activation and labour. Our objective is to investigate the interactions between CRH and PGs in human pregnant myometrium and thereby explore the mechanisms of uterine activation for labour. We intend to identify targets for intervention to delay preterm birth. Recently we found that PGF and its receptor, PTGFR, are points of convergence of several pathways and also amplifiers of uterine activation (i.e. they stimulate the expression of uterine activation factors). Studies on drugs that delay preterm labour Most drugs used by clinicians to delay preterm labour and prolong pregnancy are quite ineffective or have several maternal and fetal side effects. In part this is due to the fact that nearly all were designed originally for some other health problem. Contemporary strategies for designing better, more specific and safer drugs to delay preterm labour include targeting events that occur earlier in the cascade of physiological and biochemical events leading to labour and to target mechanisms that are specific to uterine tissues. In our collaborative efforts with Drs. Sylvain Chemtob from the University of Montreal and Gerlinde Metz from the University of Lethbridge, we are finding that targeting cytokine receptors is effective in delaying preterm and term labour in rodent models, and targeting the receptor for PGF, PTGFR, in the uterus is producing very promising results and possibly new drugs that are commercializable.

Research Interest

parturition, immunology, leukocytes, perinatal programming, rat model, Pregnancy, immune system, IL-1, IL-6, monocytes, Preterm birth, inflammatory mechanisms, cytokines, Preterm birth, inflammatory mechanisms, cytokines,, preterm delivery, Stress questionnaire, China, abuse, stress, resiliency, brain, perinatal, programming,, Studentship, timing of birth