Project Details
Description
1. 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) on stem cell level (Collaboration with J.P. Medema). Recently, the key mechanisms leading to IM have been identified. Currently, diverse transgenic and physiological novel mouse models for Barrett’s esophagus are being developed and lineage tracing studies are performed (Collaboration with prof. H. Clevers Hubrecht Institute Utrecht; prof. Dr. K. Wang and N. Buttar, Mayo Clinic, Rochester, USA). In addition, molecular targets for imaging and treatment of benign and malignant Barrett’s esophagus are being developed and the initial in vitro testing is being performed (collaboration with). 2. 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. At the end of 2010 the AMC cohort of over 160 BE patients has reached an average 5-year prospective follow up. Based on this data a patent is filed on a novel FISH biomarker assay which has a high long term prognostic power (OR >5) to stratify Barrett patients in low and high risk groups (disclosure will be on the 6th of Oct on the NVGE, Nederlandse Vereniging voor Gastroenterologie). Currently, this prognostic marker set is being validated in a cohort of >300 unselected BE from six community hospitals, which will reach 5 year FU at the end of 2012. An interim analysis is highly promising. In addition the marker set will be validated in a UK population of 500 Barrett patients, collaboration with. Dr. R. Fitzgerald, Cambridge, UK. Also NIH funding is applied for to test the marker set in a US population, collaboration with K.K. Wang Mayo Clinic, Rochester USA. 3.
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, USA, collaboration with Dr. K. Wang. 4. 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.
Theme: Gastro-intestinal diseases and oncology Manuscripts recently accpeted for publication: "A novel pSMAD/CDX2 complex is essential for the intestinalization of epithelial metaplasia."Luigi Mari, Francesca Milano, Kaushal Parikh, Danielle Straub, Vincent Everts, Kees K. Hoeben, Paul Fockens, Navtej S. Buttar, Kausilia K. Krishnadath. Cell Reports Manuscript accepted 2014 "Suppression of p21Rac signaling and increased innate immunity mediate remission in Crohn’s disease.K. Parikh'; R. Somasundaram; G. zhoulu; G.M. Fuhler; J.J. Deuring; Blokzijl, T; Regeling, E.J. Kuipers; Weersma, RK; V.J.A.A. Nuij; M.M. R.B. Parikh - Alves; L. Vogelaar; Visser, L; C.G. de Haar; K.K. Krishnadath; C.J. van der Woude; Dijkstra, G, M.P. Peppelenbosch, Science Translational Medicine Manuscript accepted 2014
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) on stem cell level (Collaboration with J.P. Medema). Recently, the key mechanisms leading to IM have been identified. Currently, diverse transgenic and physiological novel mouse models for Barrett’s esophagus are being developed and lineage tracing studies are performed (Collaboration with prof. H. Clevers Hubrecht Institute Utrecht; prof. Dr. K. Wang and N. Buttar, Mayo Clinic, Rochester, USA). In addition, molecular targets for imaging and treatment of benign and malignant Barrett’s esophagus are being developed and the initial in vitro testing is being performed (collaboration with). 2. 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. At the end of 2010 the AMC cohort of over 160 BE patients has reached an average 5-year prospective follow up. Based on this data a patent is filed on a novel FISH biomarker assay which has a high long term prognostic power (OR >5) to stratify Barrett patients in low and high risk groups (disclosure will be on the 6th of Oct on the NVGE, Nederlandse Vereniging voor Gastroenterologie). Currently, this prognostic marker set is being validated in a cohort of >300 unselected BE from six community hospitals, which will reach 5 year FU at the end of 2012. An interim analysis is highly promising. In addition the marker set will be validated in a UK population of 500 Barrett patients, collaboration with. Dr. R. Fitzgerald, Cambridge, UK. Also NIH funding is applied for to test the marker set in a US population, collaboration with K.K. Wang Mayo Clinic, Rochester USA. 3.
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, USA, collaboration with Dr. K. Wang. 4. 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.
Theme: Gastro-intestinal diseases and oncology Manuscripts recently accpeted for publication: "A novel pSMAD/CDX2 complex is essential for the intestinalization of epithelial metaplasia."Luigi Mari, Francesca Milano, Kaushal Parikh, Danielle Straub, Vincent Everts, Kees K. Hoeben, Paul Fockens, Navtej S. Buttar, Kausilia K. Krishnadath. Cell Reports Manuscript accepted 2014 "Suppression of p21Rac signaling and increased innate immunity mediate remission in Crohn’s disease.K. Parikh'; R. Somasundaram; G. zhoulu; G.M. Fuhler; J.J. Deuring; Blokzijl, T; Regeling, E.J. Kuipers; Weersma, RK; V.J.A.A. Nuij; M.M. R.B. Parikh - Alves; L. Vogelaar; Visser, L; C.G. de Haar; K.K. Krishnadath; C.J. van der Woude; Dijkstra, G, M.P. Peppelenbosch, Science Translational Medicine Manuscript accepted 2014
| Status | Active |
|---|---|
| Effective start/end date | 1/01/2007 → … |