Episomal-Persistent DNA in Cancer- and Chronic Diseases

Research Group Episomal-Persistent DNA in Cancer- and Chronic Diseases

Dr. Timo Bund

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The research group of Episomal-Persistent DNA in Cancer- and Chronic Diseases aims at identifying and characterizing disease-associated persistent circular DNA of infectious agents in human materials. Recent studies suggest an involvement of such agents in the development of chronic neurodegenerative diseases (Manuelidis et al. (2011), Yeh et al. (2017)). Besides the isolation of such DNAs, central questions remain, whether and in which way, these DNA-sequences and their gene products contribute to the development of certain pathologies. Proof for a direct link between an infection with these agents and a specific disease may open new avenues for intervention (vaccination, identification of patients at risk and targeted therapy).

Numerous novel episomal DNA-sequences related to single-stranded circular DNA viruses, but also to specific bacterial plasmids have been isolated from milk and bovine sera therefore termed Bovine Meat and Milk Factors or BMMFs (Funk et al.; Gunst et al.; Lamberto et al.; Whitley et al.; (2014) ; Falida et al. (2017)). The high degree of homology between isolates from milk, bovine sera and human tissue or serum points at the consumption of bovine meat or dairy products as potential route of transmission. The global epidemiology of some common cancers (e.g. colon and breast cancer) could suggest a zoonotic origin of these conditions (zur Hausen and de Villiers, 2015; zur Hausen, Bund and de Villiers, 2017). Additionally, BMMFs have been shown to persist in human cells along with detection of BMMF RNA and protein products as well as BMMF-reactive antibodies in human blood (Eilebrecht et al. 2018). This might hint at a broad exposition of humans towards such bioactive BMMF agents.

Our research covers molecular biology, cell biology, immunology as well as high throughput methodology (DNA/RNA next generation sequencing, mass spectrometry, protein/DNA/RNA interaction screening) in order to characterize the novel DNA-sequences and their interactions with the host cell. In addition, serological and seroepidemiological studies are conducted to receive more information on immune interactions between the human host and the isolated agents.

FUTURE OUTLOOK
Our studies aim at identifying infectious agents for common human cancers (specifically colon and breast cancer) and for chronic neurological diseases (specifically Multiple Sclerosis, Parkinson’s Disease, Alzheimer’s Disease). The definition of new clinical screening assays as well as the establishment of an infection system based on the new agents represents the most important milestones enabling new diagnostic tools, but also novel approaches to prevention and disease therapies in future.

Contact

Dr. Timo Bund
Episomal-Persistent DNA in Cancer- and Chronic Diseases (F200)
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 280
69120 Heidelberg
Tel: +49 6221 42 4655

Selected Publications

  • Eilebrecht, S., Hotz-Wagenblatt, A., Sarachaga, V., Burk, A., Falida, K., Chakraborty, D., Nikitina, E., Tessmer, C., Whitley, C., Sauerland, C., Gunst, K., Grewe, I., Bund, T., Expression and replication of virus-like circular DNA in human cells, Scientific Reports, 8:2851, 2018.
  • zur Hausen H., Bund T. and de Villiers, E.M. Infectious Agents in Bovine Red Meat and Milk and Their Potential Role in Cancer and Other Chronic Diseases. Current Topics in Microbiology and Immunology, 407, 83-116, 2017.
  • zur Hausen, H. and de Villiers, E.M. Dairy cattle serum and milk factors contributing to the risk of colon and breast cancers. Int J Cancer, 137(4), 959-67, 2015.
  • zur Hausen, H.: What do breast and CRC cancers and MS have in common? Nature Rev. Clinical Oncology, 12(10), 569-70, 2015.
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