The main goal of our research is to contribute to the understanding of the molecular mechanisms leading to cancer and to identify proteins that are required for cancer maintenance as potential new targets for therapy. Over the years, our group has made several important discoveries, including the identification and molecular characterization of several families of chromatin-associated proteins and their role in stem cells and cancer. In addition to providing novel insights into mechanisms regulating transcription, stem cell identity and differentiation, our work has led to the establishment of a biotech company EpiTherapeutics, which in 2015 was acquired by Gilead Inc. Moreover, we hope that our research can play a role in developing new therapies for cancer patients.
Our major model systems include embryonic stem cells, neural stem cells and cells of the hematopoietic system as well as sophisticated mouse models for tumors of the central nervous system and leukemia. We characterize the molecular mechanisms of cancer-relevant chromatin-associated proteins, perform genetic screens to identify and characterize novel factors required for tumor maintenance, and collaborate with clinicians and biotech companies to translate our findings into the clinic. Ongoing projects include:
1. Molecular characterization of chromatin-associated proteins and their impact on histone modifications, DNA methylation, transcriptional regulation and cell fate decisions
2. Development and characterization of mouse models of cancer, including patient-derived xenografts and genetically engineered models of acute myeloid leukemia and brain cancers
3. Identification and molecular characterization of novel factors involved in the maintenance of embryonic and adult stem cells, acute myeloid leukemia and tumors of the central nervous system
4. Development and characterization of small molecule inhibitors targeting several families of chromatin-associated enzymes
Link to ORCID (http://orcid.org/0000-0003-1975-6097)
Højfeldt J, Laugesen A, Willumsen BM, Damhofer H, Hedehus L, Tvardovskiy A, Mohammad F, Jensen ON & Helin K. Accurate H3K27 methylation can be established de novo by SUZ12-directed PRC2. Nature Structural & Molecular Biology. (2018)
Mohammad F, Weissmann S, Leblanc B, Pandey DP, Højfeldt, JW, Comet I, Zheng C, Johansen JV, Rapin N, Porse BT, Tvardovskiy A, Jensen ON, Olaciregui NG, Lavarino C, Suñol M, de Torres C, Mora J, Carcaboso AM & Helin K. EZH2 is a potential therapeutic target for H3K27M-mutant pediatric gliomas. Nature Medicine 4, 483-492, doi: 10.1038/nm.4293 (2017).
Agger K, Miyagi S, Pedersen MT, Kooistra SM, Johansen JV & Helin K. Jmjd2/Kdm4 demethylases are required for expression of Il3ra and survival of acute myeloid leukemia cells. Genes & Development 30, 1278-1288, doi:10.1101/gad.280495.116 (2016).
Pedersen MT*, Kooistra SM*, Radzisheuskaya A, Laugesen A, Johansen JV, Hayward DG, Nilsson J, Agger K & Helin K. Continual removal of H3K9 promoter methylation by Jmjd2 demethylases is vital for ESC self-renewal and early development. The EMBO Journal 35, 1550-1564, doi:10.15252/embj.201593317 (2016).
Rasmussen KD, Jia G, Johansen JV, Pedersen MT, Rapin N, Bagger FO, Porse BT, Bernard OA, Christensen J & Helin K. Loss of TET2 in hematopoietic cells leads to DNA hypermethylation of active enhancers and induction of leukemogenesis. Genes & Development 29, 910-922, doi:10.1101/gad.260174.115 (2015).
Riising EM, Comet I, Leblanc B, Wu X, Johansen JV & Helin K. Gene silencing triggers polycomb repressive complex 2 recruitment to CpG islands genome wide. Molecular Cell 55, 347-360, doi:10.1016/j.molcel.2014.06.005 (2014).
Wu X, Johansen JV & Helin K. Fbxl10/Kdm2b recruits polycomb repressive complex 1 to CpG islands and regulates H2A ubiquitylation. Molecular Cell 49, 1134-1146, doi:10.1016/j.molcel.2013.01.016 (2013).
Williams K, Christensen J, Pedersen MT, Johansen JV, Cloos PA, Rappsilber J & Helin K. TET1 and hydroxymethylcytosine in transcription and DNA methylation fidelity. Nature, 473, 343-8.
Pasini D, Cloos PA, Walfridsson J, Olsson L, Bukowski JP, Johansen JV, Bak M, Tommerup N, Rappsilber J & Helin K (2010). JARID2 regulates binding of the Polycomb repressive complex 2 to target genes in ES cells. Nature 464, 306-310.
Selected recent reviews
Mohammad F & Helin K. Oncohistones: drivers of pediatric cancers. Genes and Development 23-24, 2313-2324. (2017).
Helin K & Minucci S. The role of chromatin-associated proteins in cancer. Annual Reviews Cancer Biology 1, 355–77, (2017).
Comet I, Riising E, Leblanc B & Helin K. Maintaining cell identity: PRC2 regulation of transcription and cancer. Nature Reviews Cancer 12, 803-810 (2016).
Laugesen A, Hojfeldt JW & Helin K. Role of the Polycomb Repressive Complex 2 (PRC2) in Transcriptional Regulation and Cancer. Cold Spring Harbor perspectives in medicine (2016).
Rasmussen KD & Helin K. Role of TET enzymes in DNA methylation, development, and cancer. Genes & development 30, 733-750 (2016).
Laugesen A & Helin K. Chromatin repressive complexes in stem cells, development, and cancer. Cell stem cell 14, 735-751 (2014).
Helin K & Dhanak D. Chromatin proteins and modifications as drug targets. Nature 502, 480-488 (2013).
Jobs in Helin Group
Helin lab on twitter
Article from BioZoom, June 2018 by Helene Halkjær Jensen (in Danish) :"Det danske ’Nobel-center’: en overvældende satsning"
Radio program "Hjernekassen" P1: Kristian Helin on Epigenetics. Host: Peter Lund Madsen (in Danish)
Kristian Helin at The Royal Academy of Science (in Danish):
Radio program, Kristian Helin with Lone Frank (in Danish) https://www.radio24syv.dk/programmer/24-spoergsmaal-til-professoren/16777041/vi-skal-laengere-ind-helt-ind-i-cellen-kristian
Article from Politiken 15 May, 2015 by Henrik Larsen (in Danish) "Genetisk fejl spiller central rolle ved blodkræft"??
Collaborative research projects
The Helin research group is involved in several large collaborative research projects and networks:
Chromatin proteins as drug targets for glioblastoma (Brain Tumor Charity)
Development of Tailored Therapeutics for the Treatment of Cancer (Innovation Fund Denmark: Grand Solutions)
Our research is supported by: