Research
Oxytocin and vasopressin signalling in human myometrium
The neuropeptide hormones, oxytocin and vasopressin are powerful uterine stimulants. The molecular mechanisms underlying oxytocin signalling in the uterus remains one of the key focuses of my research. Using novel human vasopressin and oxytocin receptor-selective peptides (designed and synthesised by my collaborator, Ass Prof Markus Muttenthaler, University of Vienna) I am elucidating the contribution of these receptors to human myometrial contraction. The primary aim of the work is to identify the importance of each receptor subtype in order to better inform the design of new therapies targeting the oxytocin receptor for the inhibition of preterm labour contractions (tocolytics) or for stimulation of contractions (uterotonics) in cases of labour dystocia.
Combining tocolytics for preventing preterm birth
Many treatments currently in use for inhibiting preterm labour contractions lack utero-specificity and have a short window of use due to adverse maternal or fetal side effects. Combination tocolytics which target different intracellular signalling pathways may produce additive inhibitory effects, allowing for lower therapeutic doses to be used and reduce these side-effects. I am currently exploring different treatment combinations in human myometrium, including a novel hydrogen sulphide-releasing derivative of the non-steroidal anti-inflammatory drug, naproxen, to assess efficacy and determine which treatment combination is most promising.
The myometrial transcriptome in singleton and twin pregnancy
A greater understanding of why twins are at high risk of preterm delivery and better modes of treatment and prevention are urgently needed. Key to this is determining the differing pathophysiological mechanisms of preterm birth, including the role of the myometrium and premature uterine contraction in twin pregnancy. To address this, I am exploring differences in the human myometrial transcriptome between singleton and twin pregnancies at term and preterm using cutting edge technologies and high-throughput RNA sequencing (RNASeq).