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Antoaneta Belcheva

'Antoaneta Belcheva obtained her PhD in Biochemsitry from York University (Toronto, Canada) in 2009. In the laboratory of Dr. Dasantila Golemi-Kotra she studied the molecular mechanism of signal transduction of VraSR, a system that mediates antibiotic resistance in Staphylococcus aureus. 'She did her post-doctoral training with Dr. Alberto Martin at the University of Toronto (Toronto, Canada) where she explored the role of gut microbes in colon cancer development'. In 2015 Antoaneta joined the Department of Biochemistry and Molecular Biology at SDU as an Assistant Professor.

Head of research: Assistant professor Antoaneta Belcheva

PhD Fellow Katrine Nørgaard
PhD Fellow Maria Lopez Chiloeches

Postdoc Carolin Müller

Gut microbiota and colon cancer

Colon cancer is the third most common cancer and leading cause of deaths in the world. Recent studies have revealed that the complex interactions between gut microbiota, diet, host immune system and host genetics are at the root of the colon cancer etiology. Inactivation of Mismatch repair (MMR) genes are the most common lesions in hereditary nonpolyposis colon cancer (HNPCC, i.e. Lynch Syndrome), and occur in ~20% of sporadic colon cancer. However, based on the known roles of MMR pathway, it is unclear why MMR inactivation predisposes to colon cancer more so than to other cancers. One possibility is for an unusual interplay between MMR deficiency and the colon epithelial cell microenvironment. The goal of our laboratory is to better understand how gut microbes influence the homeostasis in MMR deficient colonic epithelium and contribute to CRC development. In particular, we are interesting in elucidation the role of bacterially-produced metabolites in colon cancer. This knowledge will ultimately shed light on the complex etiology of CRC development and will open new opportunities for development of more personalized cancer therapies and preventive protocols.

Current research projects

Colorectal cancer (CRC) development has a complex etiology that has been linked with gut microbiota, diet, host immune system and host genetics. How these factors cross-talk to mediate CRC development remains unknown. The most frequent genetic lesions associated with CRC occur in the adenomatous polyposis coli (APC) gene and in genes involved in the mismatch repair (MMR) pathway such as MutS homologue 2 (MSH2). Interestingly, the mechanistic linkage between MMR-deficiency and the etiology of CRC still remains elusive. We are trying to understand how microbiota and diet intersect with host genetics to modulate CRC development in APCMin/+MSH2-/- mouse model. Previously, we found that altering gut microbiota composition reduces CRC in APCMin/+MSH2-/- mice, and that a diet low in carbohydrates phenocopies this effect. Our results indicate that butyrate-producing gut microbiota provide metabolites such as butyrate that have the capacity to fuel hyperproliferation of APCMin/+MSH2-/- colonocytes. Our data point to a novel link between microbial metabolism, diet and host genetics, however, the molecular aspects of these interactions still remain to be explored. Our group will attempt to understand the mechanism through which bacterially-produced metabolites regulate proliferation in APCMin/+MSH2-/- colon epithelial cells and contribute to colon cancer development in this mouse model. We take a multidisciplinary approach including cell biology, biochemistry and molecular biology methods to examine the complex interactions between gut microbiota and host genetics in the context of colon cancer.

Selected publications

Gut microbial metabolism drives transformation of Msh2-deficient colon epithelial cells 
Belcheva A., Irrazabal T., Robertson S., Streutker C, Geddes K., Maughan H., Moriyama E., Rubino S., Kumar S., Green B., Pezo R., Milosevic M., Edelmann W., Navarre W., Wilson B., Girardin S., Wolever T., Guttman D., Philpott D., Martin A. Cell, 2014, 158(2): 288-299.

The multifaceted role of the intestinal microbiota in colon cancer 
Irrazabal T., Belcheva A., Girardin S., Martin A., Philpott D. Mol Cell, 2014, 54(2): 309-320.

Elevated Incidence of Polyp Formation in APC(Min/+)Msh2-/- Mice Is Independent of Nitric Oxide-Induced DNA Mutations 
Belcheva A., Green B., Weiss A., Streutker C., Martin A. PLoS One, 2013, 8(5).

A full list of publications by Assistant professor Antoaneta Belcheva can be found here.

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