Hepatic encephalopathy (HE) is a serious neurological condition caused by liver failure, and affecting humans and companion animals. Patients suffering this multifaceted disorder present with hyperammonaemia and elevated cytokines, leading to astrocyte swelling in the CNS, ataxia, seizures, cognitive dysfunction and coma. Surgery is effective in treating the diseased liver, yet long term changes in CNS function can prevail. This interdisciplinary project (physiology & genetics) takes a genomic approach to investigate how HE affects CNS gene expression and epigenetic changes, using next generation sequencing approaches (RNA-seq/ATAC-seq) and bioinformatic analyses to identify regulatory pathways and causal networks for this life-threatening condition.
R Strickland, MS Tivers, SE Adamantos, TR Harcourt-Brown, RC Fowkes, VJ Lipscomb 2018 Incidence and Risk Factors for Post-Attenuation Neurological Signs in 253 Dogs with a Single Congenital Portosystemic Shunt. J Vet Surg. 47(6):745-755. doi: 10.1111/vsu.12925.
Cabrera-Pastor A, Arenas YM, Taoro-Gonzalez L, Montoliu C, Felipo V 2019 Chronic hyperammonemia alters extracellular glutamate, glutamine and GABA and membrane expression of their transporters in rat cerebellum. Modulation by extracellular cGMP. Neuropharmacology. pii: S0028-3908(19)30010-3. doi: 10.1016/j.neuropharm.2019.01.011
Saint-Jean, L., Barkas, N., Harmelink, C., Tompkins, K.L., Oakey, R.J. and Baldwin, H.S. Myocardial Differentiation is Dependent upon Endocardial Signalling During Early Cardiogenesis in vitro. Development. 2019 May 8;146(9). pii: dev172619. doi: 10.1242/dev.172619. This paper describes our execution of RNA-seq and its data analysis.
Prickett, A.R., Barkas, N., McCole, R.B., Hughes, S., Amante, S.M., Schulz, R., and Oakey, R.J. Genomewide and parental allele specific analysis of CTCF and Cohesin binding sites in mouse brain reveals a tissue-specific binding pattern and an association with differentially methylated regions. Genome Research 2013. 23(10):1624-1635. PMID: 23804403. This paper illustrates the group understands how to look at epigenetic marks genomewide.