Deciphering the Mechanisms of Developmental Disorders
My scientific interest lies in congenital anomalies and in the 'developmental circumstances' leading to normal or abnormal embryonic development. I focus on Congenital Heart Disease (CHD), the most common birth defect, affecting almost 1% of live-born children. Although it is one of the major causes of infant mortality and despite extensive studies, the aetiology of about 75% of CHD cases still remains undiscovered. What is known is that CHD is a multifactorial disease and as such it may arise from a combination of genetic components (mutations in different genes, copy number variation, miRNA) and from the interactions between genetic and non-genetic (environmental) factors present during embryogenesis. My work dissects the causes of human CHD by identifying and understanding the genetic bases of cardiogenesis in murine embryos carrying either targeted (eg knockout) or random mutations (eg ENU-generated), showing cardiovascular developmental anomalies. I then investigate the mechanisms through which these mutations affect heart development. I also investigate whether epigenetic changes caused by embryo environment may expose an abnormal phenotype in otherwise normal heterozygous animals, thus elucidating why CHD has a variable penetrance in humans.
For several years, I have been involved in the high throughput phenotyping screens aiming to find new cardiac genes (random mutagenesis-based) or to establish a cardiovascular function of known genes (targeted mutagenesis). This work led to identification of several new genes crucial for cardiogenesis (eg Pcsk5, Tll1, Zic2, Inpp5a), which are now being investigated further to understand how they influence the formation of embryonic heart. One of my specialisations is phenotyping embryos scanned with magnetic resonance imaging (MRI), micro computed tomography (µCT) and high resolution episcopic microscopy (HREM). I am a member of the 'Deciphering the Mechanisms of Developmental Disorders' (DMDD) international research programme, established to study embryonic and perinatal lethal mutant mouse lines produced by the Sanger Institute Mouse Genetics Project (MGP).
My other activities include teaching medical students on 'The development of the cardiovascular system and its relevance to congenital heart disease' within the GE Cardiovascular Course. I am also a member of RDM Cardiovascular Medicine Athena Swan committee.
I graduated in 1994 from the University of Wroclaw (Poland) with an MSc in Biotechnology. In 1999, I completed my PhD in Animal Breeding and Genetics at the Wroclaw University of Environmental and Life Sciences (Poland). Following postdoctoral training at the University of Arkansas for Medical Sciences (Little Rock, USA) where I worked on genetics of bone mineral density, I came to Oxford in 2005 and have been working on Congenital Heart Disease in Prof Shoumo Bhattacharya's Group ever since.
A staging system for correct phenotype interpretation of mouse embryos harvested on embryonic day 14 (E14.5).
Geyer SH. et al, (2017), J Anat, 230, 710 - 719
Pcsk5 is required in the early cranio-cardiac mesoderm for heart development.
Szumska D. et al, (2017), BMC Dev Biol, 17, 6 - 6
ASPP2 deficiency causes features of 1q41q42 microdeletion syndrome.
Zak J. et al, (2016), Cell death and differentiation
Functional analysis of AEBP2, a PRC2 Polycomb protein, reveals a Trithorax phenotype in embryonic development and in ES cells
Grijzenhout A. et al, (2016), Development
Deciphering the mechanisms of developmental disorders: phenotype analysis of embryos from mutant mouse lines.
Wilson R. et al, (2016), Nucleic Acids Res, 44, D855 - D861