Henrik Semb – University of Copenhagen

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Henrik Semb

DanStem Executive Director, Professor of Human Stem Cell Biology

semb@sund.ku.dk

Link to the Semb Laboratory Homepage

Research Profile

With a career spanning over 15 years Henrik Semb’s multi-disciplinary approach to research has contributed to the advancement of several scientific fields. The lab has used a combination of in vivo and in vitro tools to decipher a range of cellular mechanisms, from tumor cell invasion and metastasis, to basic mechanisms in morphogenesis and differentiation during organogenesis. Henrik’s main goal is to understand the basic fundamental cellular and molecular mechanisms of organogenesis. Examples of recent ground-breaking discoveries in this area include Kesavan et al Cell, 2009, Funa et al Cell Stem Cell, 2015, and Löf-Öhlin et al Nat Cell Biol, 2017. Most recently, the lab has identified how mechanosignaling, via integrins, acts as a gate-keeper for pancreatic progenitor fate decisions (Nature, in press). Henrik’s long-term interest and experience in translating basic research results (e.g. Ameri et al Cell Reports, 2017) into clinical applications has also led to an ambitious program on human pluripotent stem cell-based cell therapy in Type 1 Diabetes. As director of the Danish Stem Cell Centre (Danstem) Henrik encourages an integrated research environment both between and within research groups

Grants and Awards

Henrik Semb’s scientific achievements in pancreas development and the beta cell biology field have been recognized by many international and national grant-awarding bodies throughout his research career, including; the EU, EMBO, Swedish Foundation for Strategic Research, the Swedish Government, the US National Institute of Health (NIH) and the Juvenile Diabetes Research Foundation. Currently Henrik is the Executive Director of Danstem, which is funded by the Novo Nordisk Foundation for a 10-year period. From 2011-2016 Henrik headed the a Section for Strategic Translational Stem Cell Research and Therapy, which was funded by a 6-year grant from the Danish Council for Strategic Research. He coordinated the collaborative EU FP7 project HumEn between 2014 and 2017 with the aim of achieving robust generation of functional beta cells from hPSCs. Lundbeckfonden awarded a 3-year project grant to the Semb lab to investigate how an endocrine cell’s niche directs fate choice to specific hormone producing differentiated cells and the Danish Council for Independent Research, Medical Sciences (FSS) awarded project grants in 2013 and 2016 for work related to investigating the role of polarity during pancreas progenitor cell differentiation.

Academic Activities 

In addition to leading his research group and the centre, Henrik is also committed to engaging in the wider stem cell and pancreas research field. Henrik has served as a member of the International Stem Cell Initiative steering committee and serves as an Editorial Board member of Stem Cells and Stem Cell Reports. He also engage in various outreach and educational activities to explain the need for basic research, how it related to translational applications and the risks with unrealistic expectations for rapid solutions to new stem cell-based therapies.

Supervision of doctoral theses and postdoctoral fellows

The Semb lab is a well-established, thriving research environment that has fostered the careers of many scientists. Currently Henrik has supervised a total of 25 Postdoctoral Fellows (7 present), and 19 PhD students (4 present).

Scientific Alumni:

  • Dr Jacqueline Ameri – Co-founder of Pancryos, a spin-out arising from the Novo Nordisk Foundation Center for Stem Cell Biology (DanStem)
  • Dr Karen Schachter – Stem Cell Scientist at Novo Nordisk, Denmark,
  • Dr Christy Prawiro - Post-doctoral Research in Human Embryonic Stem Cell and Pancreatic Differentiation at Novo Nordisk, UK,
  • Dr Zarah Löf Öhlin - Molecular biologist at Region Örebro County - Clinical Research Laboratory,
  • Dr Oliver Lieven - Lecturer at the University of Münster,
  • Dr Elin Jaensson Gyllenbäck - Senior Research Scientist at BioInvent International AB,
  • Dr Pedro Rifes - Post.Doc at the University of Copenhagen, Agnete Kirkeby Lab,
  • Dr Gokul Kesavan - Post.Doc at Technische Universität Dresden,
  • Dr Fredrik Wolfhagen-Sand - Senior Research Scientist at Novo Nordisk AS,
  • Dr. Thomas Greiner - Researcher at the University of Gothenburg,
  • Dr. Martina Johanesson - Researcher, currently unemployed,
  • Dr. Jenny Ekberg - QA Professional at Novo Nordisk,
  • Dr. Yvonne Fisher - Managing Editor at Stem Cell Reports,
  • Dr. Siqin Wu - Researcher at Spiber Technologies AB,
  • Dr. Sune Kobberup - Senior Research Scientist at Novo Nordisk AS,
  • Dr. Maria Kraft - Scientific Officer at Novo Nordisk Foundation,
  • Dr. Katja Hess - Investigation Manager at Sandoz GmbH,
  • Dr. Jenny Johansson - Post Doc at Lund University,
  • Dr. Karin Norrman - Senior Research Scientist at Novo Nordisk AS,
  • Dr. Gabriella Brolén - Team Leader at Astra Zeneca, Göteborg,
  • Dr. Wan Chun Li - Assistant Professor, Department of Dentistry, National Yang Ming University,
  • Dr. Anders Ståhlberg - Associate Professor at the University of Gothernburg,
  • Dr. Josefina Edsbagge - Senior Scientist, Team Leader at Cellectis,
  • Dr. Xiaojie Xian - Researcher at Lund University,
  • Dr. Maria Harrie (Hammarström) - Clinical researcher at McNeil AB,  
  • Dr. Farzad Esni - Associate Professor of Surgery at the University of Pittsburgh,
  • Dr. Dahl - Senior research engineer at Umeå University,
  • Dr. Damert - Group leader at Babes-Bolyai-University, Romania,
  • Dr. Håkansson - SP technical Institute of Sweden, Medical device technology.

Entrepreneurial Achievements

Professor.Semb acted as a scientific advisor within Cellartis AB, a company which he co-founded. Cellartis was a Gothenburg based SME with 62 employees and an annual revenue of €6million that commercialized various human ES cell applications. Cellartis was purchased by Cellectis (France) in 2011, Cellectis was subsequently bought in 2014 by Takara bio inc.

As part of a 3-party collaboration between Lund University (Semb), Novo Nordisk a/s and Cellartis/Cellectis Henrik worked to develop a hESC-based cell therapy for diabetes (2008-2013).

Professor Semb is also a cofounder (along side Dr Jacqueline Ameri) of a spin-out company arising from the Novo Nordisk Foundation Center for Stem Cell Biology (DanStem), at the University of Copenhagen. The company is aiming to develop a next generation stem cell derived allogeneic cell therapy (PanINSULA™) for type 1 diabetes.

Publications and Patents

Total number of published, peer reviewed publications and reviews: 68, H-factor: 39
Total number of patents applied for and/or granted: 8, of note are patents by Mamidi and Semb (Oct 2016) that describe a “method for differentiation of cells into insulin-producing cells and a method for treating a metabolic disorder”. Also that of Ameri and Semb (Oct 2016) that details an ‘invention that relates to a method for isolating bona fide pancreatic progenitor cells’.

Key Recent Discoveries

Mamidi, A., Prawiro, C., Seymour, P.A., de Lichtenberg, K.H., Jackson, A., Serup, P., and Semb, H. (2018). Mechanosignalling via integrins directs fate decisions of pancreatic progenitorsNature, doi: 10.1038/s41586-018-0762-2

Löf Öhlin, Zarah, Pia Nyeng, Matthew Bechard, Katja Hess, Eric Bankaitis, Thomas U. Greiner, Jacqueline Ameri, Christopher V. Wright & Henrik Semb (2017). Context-specific regulation of apicobasal polarity by EGFR orchestrates epithelial morphogenesis and cellular fate. Nature Cell Biology, doi: 10.1038/ncb3628.

Ameri, Jacqueline, Rehannah Borup, Christy Prawiro, Cyrille Ramond, Karen A. Schachter, Raphael Scharfmann & Henrik Semb (2017). Efficient Generation of Glucose-Responsive Beta Cells from Isolated GP2+ Human Pancreatic Progenitors. Cell Reports, 19(1), 36-49, doi:10.1016/j.celrep.2017.03.032. 

Funa, N.S*., Schachter, K.A*., Lerdrup, M., Ekberg, J., Hess, K., Dietrich, N., Honoré, C., Hansen, K., and Semb H. β-Catenin Regulates Primitive Streak Induction through Collaborative Interactions with SMAD2/SMAD3 and OCT4. Cell Stem Cell, 2015 Jun 4 16(6):639-52. *authors contributed equally.

This study provides mechanistic insight into how Wnt signalling controls early cell lineage decisions, namely that of neural crest cells.

Kesavan, G., Lieven, O., Mamidi, A., Öhlin, Z.L., Johansson, J.K., Li, W.C., Lommel, S., Greiner, T.U.,and Semb, H. Cdc42/N-WASP signaling links actin dynamics to pancreatic β cell delamination and differentiation. Development. Feb;141(3):685-96, 2014.

Beta-cell delamination and Beta-cell differentiation both require tightly regulated levels of the RhoGTPase Cdc42.

Wolfhagen Sand, F., Hörnblad, A., Johansson, J.K., Lorén, C., Edsbagge, J., Ståhlberg, A., Magenheim, J., Ilovich, O., Mishani, E., Dor,Y., Proia, R.L., Ahlgren, U. and Semb, H. Growth-limiting role of endothelial cells in endoderm development. Dev Biol, 15, 267-77, 2011.

The discovery that endothelial cells limit progenitor cell expansion in several foregut-derived organs.                                                                                                                    

Ameri, J., Ståhlberg, A., Pedersen, J., Johansson, J.K., Johannesson, M., Artner, I., and Semb, H. FGF2 Specifies hESC-Derived Definitive Endoderm into Foregut/Midgut Cell Lineages in a Concentration Dependent Manner. Stem Cells, 28, 45-56, 2010.

The identification of how FGF signalling in a concentration-dependent manner controls specification of hESC-derived definitive endoderm into liver, pancreas and lung endoderm.

Kesavan, G., Wolfhagen Sand, F., Greiner, T., Johansson, J., Kobberup, S., Wu, X., Brakebusch, C., and Semb, H. Cdc42-mediated tubulogenesis controls cell specification. Cell, 139, 791-801, 2009.

The identification of the molecular machinery that controls tube formation and how tubes controls cell specification.

Xian, X., Håkansson, J., Lindblom, P., Betsholtz, C., Gerhardt, H., and Semb, H. Pericytes limit tumor cell metastasis. J. Clin. Invest. 116, 642-51, 2006.

The identification of a new model for how tumor cells trigger metastasis by perturbing pericyte-endothelial cell-cell interactions                                              

Possible Conflicts of Interest

Henrik has founded the company Diastem A/B. Diastem is largely a consultant company with Henrik Semb as the sole person in the company.