Congenital malformation: Identifying causes, disease mechanisms, and opportunities for possible prevention

Title: Congenital malformation: Identifying causes, disease mechanisms, and opportunities for possible prevention

Speaker: Professor Sally Dunwoodie AO, Victor Chang Cardiac Research Institute

Abstract: It is estimated that a third of human pregnancies are lost before term, and globally at least 4.9 million people are born each year with a severe structural birth defect. Genetic and environmental factors are known causes but for the majority causation is not investigated; when investigated, the cause is mostly not identified. Thus, almost all families and clinicians are left guessing as to the causes and consequences of these adverse pregnancy outcomes.

Focusing on patients with congenital heart disease in isolation or with extra-cardiac anomalies, we are identifying novel genetic causes via whole genome sequencing of families, functional testing of identified gene variants, and the making of mouse models. These approaches have provided families with vital information, improved our understanding of the factors that can disrupt mammalian embryogenesis, identified disease mechanism, and identified vitamin B3 as a possible preventative of some cases of adverse pregnancy outcomes.

Bio: Sally Dunwoodie is Co-Deputy Director of the Victor Chang Cardiac Research Institute (VCCRI) and Director of the Institute’s Innovation Centre. She gained a PhD researching muscle development, at the University of Sydney. She undertook postdoctoral training in embryology, with Rosa Beddington at the National Institute for Medical Research in London. At the VCCRI, she heads the Embryology Laboratory and the Congenital Heart Disease Research Program. Dunwoodie is recognised for defining genetic causes of congenital malformations having identified 21 new disease genes and thereby contributing to enhancing genetic diagnostic rates for congenital malformation globally. She explores the functional effects of human gene mutations on embryogenesis, and the impact that gene-environment interaction has on mouse embryogenesis and human congenital malformation. Dunwoodie is Co-Chair of the Australian Functional Genomics Network. She is a journal editor of Developmental Biology and Disease Models and Mechanisms. She is President of the International Society of Differentiation. In 2024 Dunwoodie was appointed as an Officer of the Order of Australia for distinguished service to medical research as an embryologist and geneticist, particularly in the field of foetal, and neonatal heart disease.