Major research lines
- Fundamental cell biological studies for understanding the biology of Barrett’s esophagus
These fundamental studies aim at understanding signalling pathways and other biological mechanisms that lead to transdifferentiation of esophageal epithelium into intestinal type of metaplasia (IM) or Barrett’s esophagus (BE). Recently, the key mechanisms leading to IM have been identified (paper subm). Currently, novel mouse models for Barrett’s esophagus are being developed. In addition, molecular targets for inhibiting and treatment of Barrett’s esophagus are being tested in the surgical rat model (collaboration with Dr. N. Buttar, Mayo Clinic, Rochester, ). In 2011, support for these studies is received from the KWF and ZonMW (Agiko). - Biological marker studies for improving surveillance of Barrett’ esophagus patients
Brush cytology specimens of BE cohorts are being screened for molecular abnormalities by using Fluorescent In Situ Hybridization (FISH). These studies have been recently awarded by two grants (KWF 2008 and NWO, preventie 2008). A panel of prognostic and diagnostic DNA FISH markers have been identified in the AMC cohort. In 2010 the AMC cohort of 160 BE patients has reached a 5-year prospective follow up. In this study a prognostic marker set is identified that in the is submitted for a patent and FDA approval for further applications. In the this marker set being validated in a cohort of >300 unselected BE from six community hospitals. - Developing novel treatment modalities for improving outcomes of GI cancer
In the field of immunotherapy, important work is being performed to improve treatment of the highly malignant esophageal adenocarcinoma and pancreatic cancer. The focus is on developing and improving Dendritic Cell (DC) immunotherapy by understanding and manipulating the tumor immune environment. In addition, in collaboration with Sanquin and the Dept. of Immunology, a phase I/IIa DC vaccination trial is being prepared for these patients. This work has been recently rewarded by a grant from the Dutch Gastroenterology Society (2008) and ‘Stichting tegen Kanker’ (2009). - Identifying genetic susceptibility genes for Barrett’s esophagus
The population at highest risk for developing BE are middle-aged Caucasian men. Certain Y-chromosome haplotypes were found as protective factors for developing BE in Dutch cohorts. These results are currently being validated in a cohort of BE patients (n=700) of the Mayo Clinic, Rochester, collaboration with Dr. K. Wang. - Research collaborator on clinical studies of Barrett’s esophagus patients
In collaboration with the group of Dr. J. Bergman, there is involvement in several ongoing clinical studies on BE. Other research lines
- Evaluation of imaging probes for future implementation in endoscopic diagnosis of dyplasia in Barrett’s esophagus.
- Studying the role of SATB1 in the metastatic behavior of GI cancesr.
- Kinome analysis of esophageal adenocarcinoma to detect targets for improving and developing novel molecular therapies.
Patents
Patent application filed for prognostic /diagnostic FISH biomarker set for Barrett patients
Members of the laboratory
- Sheila Krishnadath (Principal Investigator)
- Fransesca Milano (Postdoc)
- Akueni Davelaar (PhD-student)
- Alifyia Pacha (PhD-student)
- Kaushal Parikh (PhD-student)
- Wendy van de Luijtgaarden (PhD-student)
- Wytske Westra (PhD-student)
- Danielle Straub (technician)