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职业迁徙
个人简介
My research interests include identification and validation of new genes involved in formation and progression of cancers, particularly colorectal cancer, gynaecological cancers, melanomas, as well as other neoplasms. This involves analysis of human cancer samples, cultured cells and in vivo model systems using both comparative pathology, molecular pathology and digital pathology approaches.
Carcinogenesis involves cellular transit from normal via precursor lesions to malignant neoplasms. These transitions are usually associated with characteristic genetic and epigenetic changes. In the bowel, these include alterations to APC (>80%), the DNA mismatch repair genes MLH1 & MSH2 (~15%), KRAS (~40%), and TP53 (~60%) amongst others, and these genes also influence the regulation of proliferation, differentiation and apoptosis. In the endometrium, these include alterations to PTEN (80-90%), the DNA mismatch repair genes MLH1 & MSH2 (~30%), and KRAS (~20%), amongst others.
High throughput array and DNA sequencing analyses have identified genes that consistently show loss or gain of copy number in colorectal tumours including BRUNOL4, PARK2 and IRS2 as new genes in colorectal cancer development and progression. Sleeping Beauty transposition studies have been used to identify new tumour-related genes, including those that cooperate with mutated APC in intestinal tumour formation, with mutant Nucleophosmin in leukaemogenesis and with mutated BRAF in melanoma development. DNA methylation studies of epigenetic silencing of cancer-related genes demonstrated involvement of MLH1, MGMT, PTEN, DNMT3B and others in the WNT/APC/B-CATENIN signalling pathway in colorectal neoplasia. In vivo models of intestinal tumourigenesis were used to determine contributions to tumour formation by mutant MSH2, KRAS, RASSF1A, GNAS, PARK2, NRBP1, PKHD1 and others. Use of knockout models validated SLX4/FANCP as a new Fanconi Anaemia gene and demonstrated that the Fanconi DNA repair pathway for interstrand DNA crosslinks was shown to be critically important in repairing both acetaldehyde-induced and formaldehyde-induced DNA damage thus protecting against tumour formation. Mutant ALDH gene models confirmed the involvement of ethanol and acetaldehyde as both mutagens and promoters in intestinal and liver tumour formation. Currently, conditional MSH2 knockout models allow investigation of ethanol and acetaldehyde as mutagens and promoters in colonic tumourigenesis.
研究兴趣
论文共 326 篇作者统计合作学者相似作者
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Pranay Shah,Ross Hill,Camille Dion,Stephen J. Clark,Abdulkadir Abakir, Jeroen Willems,Mark J. Arends, Juan I. Garaycoechea,Harry G. Leitch,Wolf Reik,Gerry P. Crossan
NATURE COMMUNICATIONSno. 1 (2024)
European Journal of Cancer (2024): 114205
Scientific reportsno. 1 (2024): 309-309
Experimental and Molecular Pathology (2024): 104916
Patricia Basurto-Lozada, Martha Estefania Vázquez-Cruz,Christian Molina-Aguilar, Amanda Jiang,Dekker C. Deacon,Dennis Cerrato-Izaguirre,Irving Simonin-Wilmer, Fernanda G. Arriaga-González, Kenya L. Contreras-Ramírez, Eric T. Dawson, J. Rene C. Wong-Ramirez, Johana Itzel Ramos-Galguera,Alethia Álvarez-Cano, Dorian Y. García-Ortega, Omar Isaac García-Salinas, Alfredo Hidalgo-Miranda,Mireya Cisneros-Villanueva,Héctor Martínez-Said,Mark J. Arends,Ingrid Ferreira,Mark Tullett, Rebeca Olvera-León, Louise van der Weyden,Martin Del Castillo Velasco-Herrera,Rodrigo Roldán-Marín, Helena Vidaurri de la Cruz, Luis Alberto Tavares-de-la-Paz, Diego Hinojosa-Ugarte,Rachel L. Belote, D. Timothy Bishop, Marcos Díaz-Gay,Ludmil B Alexandrov, Yesennia Sánchez-Pérez, Gino K. In,Richard M. White, Patricia A. Possik,Robert L. Judson-Torres,David J. Adams,Carla Daniela Robles-Espinoza
crossref(2024)
VIRCHOWS ARCHIVno. 2 (2024): 287-287
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作者统计
#Papers: 324
#Citation: 13202
H-Index: 60
G-Index: 109
Sociability: 7
Diversity: 3
Activity: 85
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