BEGIN:VCALENDAR
PRODID:-//University of Otago//Events Calendar//EN
VERSION:2.0
CALSCALE:GREGORIAN
METHOD:PUBLISH
X-WR-CALNAME:University of Otago Calendar
BEGIN:VEVENT
UID:https://www.otago.ac.nz/news/events/biochemistry-seminar-emily-schulpen-phd-candidate
URL:https://www.otago.ac.nz/news/events/biochemistry-seminar-emily-schulpen-phd-candidate
DTSTART;TZID=Pacific/Auckland:20261013T120000
DTEND;TZID=Pacific/Auckland:20261013T130000
SUMMARY:Biochemistry seminar: Emily Schulpen, PhD candidate
DESCRIPTION:Hereditary diffuse gastric cancer (HDGC) is an inherited cancer syndrome caused primarily by germline mutations in CDH1, which encodes the cell-cell adhesion protein E-cadherin. Despite widespread epithelial E-cadherin expression, cancer development occurs only in the stomach and breast, with significant variation in reports of lifetime risk. This variation suggests that additional genetic and environmental factors may modify disease penetrance. This project investigated potential environmental modifiers of HDGC using pre-clinical models. A newly characterised Cdh1-heterozygous mouse model successfully recapitulated early HDGC lesions, providing a model for subsequent in vivo studies examining risk factors that may influence the functional Cdh1 allele and modify DGC penetrance. Firstly, experimental manipulation of fatty acid composition demonstrated that reducing oleic acid availability selectively reduced the viability of CDH1-null cells, suggesting that dietary fatty acid exposure may influence the behaviour and survival of cells lacking E-cadherin. Next, Vitamin D deficiency was investigated as a potential risk factor for HDGC but did not significantly alter DGC penetrance, although reduced serum vitamin D levels in Cdh1-heterozygous mice suggested possible effects of Cdh1 haploinsufficiency on nutrient absorption. In contrast, cadmium exposure significantly increased the incidence of early DGC lesions, supporting cadmium as a potential environmental risk factor for DGC in CDH1 germline mutation carriers. To investigate the tissue specificity of HDGC, transcriptomic analyses were conducted across multiple epithelial tissues following Cdh1 loss. While no definitive explanation for tissue-specific cancer susceptibility was identified, gastric tissue exhibited a significant upregulation of innate immune response pathways. Collectively, this work advances our understanding of the genetic and environmental determinants of HDGC. These results have implications for risk assessment, surveillance strategies, and future approaches to cancer prevention in individuals and families affected by HDGC. 
LOCATION:Biochemistry Seminar Room G.13 (BIG13), 710 Cumberland Street, Dunedin
END:VEVENT
END:VCALENDAR