Cell Fate

Group leader

Cecilia Sahlgren, PhD.,
Docent in Cell and Development Biology, (Åbo Akademi University).
Academy Research Fellow, Turku Centre for Biotechnology, Åbo Akademi and Turku University

Contact information

BioCity, Tykistokatu 6B,
FI-20521 Turku, Finland.
Tel. +358-2-3338611,
Fax. +358-2-3338000.
Email: cecilia.sahlgren@btk.fi

Description of Project

Cell-cell communication in development and disease: Targeting the Notch signaling pathway

We aim at understanding the basic molecular principles of signaling mechanisms regulating cell fate choices during stem cell differentiation, and how disturbances in these mechanisms link to cancer. Another important goal is to develop technology to specifically monitor and tune these signals at will in specific cell populations, in order to steer stem cell fate and curtail oncogenic activities. We are particularly interested in the role and regulation of the evolutionary conserved Notch signaling pathway, a key regulator of stem cell function and tumorigenesis. The main objectives of our research are to understand i) how the cellular microenvironment influences Notch signaling activities and how this impinges on cell identity, function and tumor progression, ii) how Notch signaling interlinks with other signaling and cellular mechanisms to fine tune and modulate the cellular response, iii) how intracellular temporal and spatial control of Notch signaling activities are achieved and to iv) develope technology platforms to regulate Notch signaling in targeted cell populations and for bioimaging of cellular functions in vivo.

Group Members

Cecilia Sahlgren (PI)
Veronika Mamaeva (Post doc)            (M.D., PhD)
Daniel Antfolk (PhD student)              (M.Sc. Bioscience)
Marika Sjöqvist (PhD student)            (M.Sc. Cell biology)
Sebastian Landor (PhD student)        (M.Sc. Biochemistry)
Christian Antila (PhD student)            (M.Sc. Bioscience)
Rasmus Niemi (PhD student)              (M.Sc. Cell biology)
Valeriy Paramonov (PhD student)      (M.D. Endocrinology)

Alumni

Martina Lerche                                   (M.Sc. Bioscience)
Jenni Niinimäki                                   (M.Sc. Cell biology)
Cecilia Haga                                         (M.Sc. Bioscience)
Sara Sarinko                                         (M.Sc. Cell biology)
Habib Baghirov                                    (M.Sc. Biomedical Imaging)
Laurel Bate-Eya                                    (M.Sc. Biomedical Imaging)
Santosh Kumar                                     (M.Sc. Biomedical Imaging)

Ongoing Projects

Funding

The Academy of Finland, Åbo Akademi University (CoE in cell stress and ageing), Turku Graduate School of Biomedical Sciences, Magnus Ehrnrooth’s Stiftelse, Sigrid Jusélius Foundation, Finnish Cancer Organizations, the Tor Joe och Pentti Borgs Foundation (Åbo Akademi University).

List of publications 2008-2015

Jessica M. Rosenholm, D.Sc.(Tech.); Riikka M. Korpi; Eveliina Lammentausta; Siri Lehtonen; Petri Lehenkari; Rasmus Niemi; Wangchuan Xiao; Jixi Zhang; Natalie Råtts; Hongchen Gu; Cecilia Sahlgren*; Roberto Blanco Sequeiros*. Novel, Fast-Processed Crystalline and Amorphous Manganese Oxide Nanoparticles for Stem Cell Labeling. Inorganic Chemistry DOI:10.1039/C5QI00033E.

Tina Gulin-Sarfraz, Jixi Zhang, Diti Desai, Jarmo Teuho, Jawad Sarfraz, Hua Jiang, Chunfu Zhang, Cecilia Sahlgren, Mika Lindén, Hongchen Gu, Jessica M Rosenholm. Combination of magnetic field and surface functionalization for reaching synergictic effects in cellular labeling by magnetic core-shell nanopsheres.  Biomaterials Science 2:1750-17600, 2014

Marika Sjöqvist, Daniel Antfolk, Saima Ferraris,  Vilma Rraklli,  Cecilia Granqvist, Christian Antila, Anders Mutvei, Susumu Y. Imanishi, Johan Holmberg, Shaobo Jin, John E. Eriksson,  Urban Lendahl and Cecilia Sahlgren. aPKC regulates Notch receptor routing  and activity in a Notch signalling dependent manner. Cell Research, 24:433-50, 2014

Oliver Wiltschka, Dominique Böcking, Rolf Brenner, Cecilia Sahlgren, Mika Lindén. Preparation, characterization, and preliminary biocompatibility evaluation of particulate spin-coated mesoporous silica films.  Macroporous and nanoporous materials in press, 188:203-209, 2014

Dominique Böcking, Oliver Wiltschka, Jenni Niinimäki, Hussein Shokry, Mika Lindén, Cecilia Sahlgren Mesoporous silica nanoparticle-based substrates for local cell directed delivery of Notch signaling modulators to control muscle stem cell differentiation. Nanoscale  6 (3):1490 – 1498, 2014

Rainer Wittig#, Felicitas Genze, Eva von Haartman, Jessica Rosenholm, Thomas Simmet, Mika Linden, Cecilia Sahlgren#. Active targeting of mesoporous silica drug carriers enhances gamma-secretase inhibitor efficacy in an in vivo model for breast cancer. Nanomedicine 9:971-87, 2014

Mamaeva, V., C. Sahlgren#, and M. Linden#. Mesoporous silica nanoparticles in medicine-Recent advances. Advanced drug delivery reviews, 65:689-702, 2013

Neeraj Prabhakar, Tuomas Näreoja , Eva von Haartman , Didem SenKaraman , Hua Jiang, Sami Koho , Tatiana A. Dolenko , Pekka Hänninen , Denis I. Vlasov , Victor G. Ralchenko , Satoru Hosomi , I Vlasov, Cecilia Sahlgren and Jessica M. Rosenholm. Core-shell designs of photoluminescent nanodiamonds with porous silica coatings for bioimaging and drug delivery II: Application. Nanoscale  5(9):3713-22, 2013

Jin, S., A.P. Mutvei, I.V. Chivukula, E.R. Andersson, D. Ramskold, R. Sandberg, K.L. Lee, P. Kronqvist, V. Mamaeva, P. Ostling, J.P. Mpindi, O. Kallioniemi, I. Screpanti, L. Poellinger, C. Sahlgren, and U. Lendahl. 2012. Non-canonical Notch signaling activates IL-6/JAK/STAT signaling in breast tumor cells and is controlled by p53 and IKKalpha/IKKbeta. Oncogene 32:4892-902, 2013
Rosenholm, J.M., V. Mamaeva, C. Sahlgren#, and M. Linden#. Nanoparticles in targeted cancer therapy: mesoporous silica nanoparticles entering preclinical development stage. Nanomedicine (Lond). 7:111-120, 2012

Wilhelmsson, U., M*. Faiz, Y. de Pablo*, M. Sjoqvist, D*. Andersson, A. Widestrand, M. Potokar, M. Stenovec, P.L. Smith, N. Shinjyo, T. Pekny, R. Zorec, A. Stahlberg, M. Pekna, C. Sahlgren, and M. Pekny. Astrocytes negatively regulate neurogenesis through the Jagged1-mediated notch pathway. Stem Cells. 30:2320-2329, 2012

Didem Sen Karaman, Diti Desai, Rajendran Senthilkumar, Emma Johansson, Natalie Råtts, Magnus Odén, John E. Eriksson, Cecilia Sahlgren, Diana Toivola, Jessica M. Rosenholm. Shape-engineering vs organic modification of inorganic nanoparticles as a tool for enhancing cellular internalization. Nanoscale Research Letters, 7:358, 2012

Sebastian Landor, Veronika Mamaeva, Anders Mutvei, Shaobo Jin, Morten Busk, Ronald Borra, Tove Grönroos, Pauliina Kronqvist, Urban Lendahl and Cecilia Sahlgren.  Hypo- and hyperactivated Notch signaling resets cellular metabolism in breast tumor cells by distinct mechanisms. Proceedings of National Academy of Sciences of the United States of America, PNAS 108:18814-9, 2011.
HIGHLIGHT Nature: A Warburgh shakeup, Nature Chemical Biology: Nat Chem Biol. 2011 Dec 15;8(1):20.

Mamaeva, V., Rosenholm, J.M., Tabe Bate-Eya, L., Bergman, L., Peuhu,E., Duchanoy, A., Fortelius, L.E., Landor, S., Toivola, D.M Lindén, M., and Sahlgren, C. Mesoporous silica nanoparticles as drug delivery systems for targeted inhibition of Notch signaling in cancer. Molecular Therapy 19:1538-46, 2011

Jessica M. Rosenholm, Cecilia Sahlgren#, Mika Linden#. Multifunctional mesoporous silica nanoparticles for combined therapeutic, diagnostic and targeted action in cancer treatment Current Drug Targets 12:1166-86, 2011

Pallari, H.M., Lindqvist, J., Torvaldson, E., Ferraris, S.E., He, T., Sahlgren, C., and Eriksson, J.E. Nestin as a regulator of Cdk5 in differentiating myoblasts. Molecular  Biology of the  Cell. 22, 1539-49, 2011

Jessica M. Rosenholm, Cecilia Sahlgren#, Mika Linden#. Towards intelligent, targeted drug delivery systems using mesoporous silicananoparticles – Opportunities & Challenges  Nanoscale, 2:1870-83, 2010

Jessica Rosenholm, Cecilia Sahlgren, Mika Lindén. Cancer cell-specific targeting of and targeted delivery by mesoporous silica nanoparticles. Highlight to Journal of Material Chemistry 14:2707-2713, 2010.

Das D, Lanner F, Main H, Andersson ER, Bergmann O, Sahlgren C, Heldring N, Hermanson O, Hansson EM, Lendahl U. Notch induces cyclin-D1-dependent proliferation during a specific temporal window of neural differentiation in ES cells. Developmental  Biology. 348:153-66, 2010

Jessica M. Rosenholm, Emilia Peuhu, Laurel Tabe Bate-Eya, John E. Eriksson, Cecilia Sahlgren#, Mika Lindén#. Cancer-Cell Specific Induction of Apoptosis using Mesoporous Silica Nanoparticles as Drug Delivery Vectors  Small 6:1234-41, 2010

Aurelie de Thonel, Saima E. Ferraris, Hanna-Mari Pallari, Susumu Y. Imanishi, Vitaly Kochin, Tomohisa Hosokawa, Shin-ichi Hisanga, Cecilia Sahlgren, and John E. Eriksson. PKCz regulates CDK5/p25 signaling during myogenesis Molecular Biology of the Cell 21:1423-34, 2010

Heather  Main,  Kian  Leong  Lee,  Henry  Yang,  Saija  Haapa-Paananen,  Henrik  Edgren, Shaobo  Jin, Cecilia  Sahlgren, Olli Kallioniemi,  Lorenz  Poellinger, Bing  Lim  and Urban Lendahl. Integration between Notch- and hypoxia-induced transcritpomes in embryonic stem cells. Experimental Cell Research 316:1610-24, 2010

Jin, S., Hanssom, E.M., Tikka, S., Lanner, F., Sahlgren, C., Fanebo, F., Baumann, M., Kalimo, H., Lendahl, U (2008) Notch signaling regulates platelet-derived growth factor receptor-β expression in vascular smooth muscle cells. Circulation Research 12:1483-1491.

Jessica M Rosenholm, Dr., Emilia Peuhu, M.Sc., John Eriksson, Prof. Dr., Cecilia Sahlgren, Dr.#, Mika Linden, Dr.# Targeted Intracellular Delivery of Hydrophobic Agents using Mesoporous Hybrid Silica Nanoparticles as Carrier Systems Nano Letters 9:3308-3311, 2009

Jessica M Rosenholm, Dr., Annika Meinander, Dr., Emilia Peuhu, M.Sc., Rasmus Niemi, Mr., John Eriksson, Prof. Dr., Cecilia Sahlgren, Dr. #, Mika Linden, Dr.# Targeting of porous hybrid silica nanoparticles to cancer cells. ACS Nano 3:197-206, 2009
Sahlgren, C, Gustafsson, M, Jin, S, Poellinger, L and Lendahl, U. Notch signaling mediates hypoxia induced tumor cell migration and invasion. (2008) Proceedings of National Academy of Sciences of the United States of America, PNAS 105:6392-7
HIGHLIGHT Science: Notching Up Tumor Progression, Science Signaling Editors Choice: Sci. Signal. 1 (18), ec163. [DOI:10.1126/stke.118ec163]

Gavin Chapman*, Lining Liu*, Cecilia Sahlgren, Camilla Dahlqvist, and Urban Lendahl. High levels of Notch signaling downregulate Numb and Numblike. Journal of Cell Biology, 175(4):535-40, 2006
Sahlgren C and Lendahl U. Notch, stem cell control and integration with other signaling mechanisms Regenerative Medicine 1 (2):195-20, 2006

Sahlgren, C, Pallari H.-M., He, T, and Eriksson J.E. A nestin scaffold links Cdk5 signaling to oxidant-induced cell death EMBO Journal 25(20):4808-19, 2006

Sahlgren, C. M., Mikhailov, A, Vaittinen, S., Hanna-Mari Pallari, Kalimo, H., Pant, H.C., Eriksson, J.E. Cdk5 regulates the organization of nestin and its association to p35. Molecular and Cellular Biology 23:5090-5106, 2003

Vaittinen, S., Lukka, R., Sahlgren, C., Hurme,T., Rantanen, J., Lendahl, U., Eriksson, J.E. and Kalimo, H. The expression of intermediate filament protein nestin as related to vimentin and desmin in regenerating skeletal muscle. Journal of Neuropathology and Experimental Neurology 60:588-597, 2001

Sahlgren, C. M.,  Mikhailov, A., Hellman, J., Chou, Y.-H., Lendahl, U., Goldman, R. D. and Eriksson, J. E. Mitotic reorganization of the intermediate filament protein nestin involves phosphorylation by cdc2-kinase. Journal of Biological Chemistry 274:16456-16463, 2001

Eliasson, C, Sahlgren, C, Berthold, C.H., Stakeberg, J, Celis, J.E., Betsholtz, C., Eriksson, J.E., and Pekny, M. Intermediate filament protein partnership in astrocytes. Journal of Biological Chemistry 274:23996-24006, 1999

Vaittinen, S., Lukka, R., Sahlgren, C., Rantanen, J., Hurme,T., Lendahl, U., Eriksson, J.E and Kalimo, H. Specific and innervation-regulated expression of the intermediate filament protein nestin at neuromuscular and myotendinous junctions in skeletal muscle. American Journal of Pathology 154:591-600, 1999

Kalimo, H., R. Lukka, S. Vaittinen, C. Sahlgren, and J. Eriksson. Distribution of intermediate filament  nestin in myofibers. Brain Pathol. 7:1119-1119, 1997

Reuter, M., Gustafsson, M.K., Sahlgren, C., Halton, D.W., Maule, A.G., and Shaw, C. The nervous system of Tricladida. I. Neuroanatomy of Procerodes littoralis (Maricola, Procerodidae): an immunocytochemical study. Invert Neurosci 1, 113-122, 1995

* Equal contribution
Shared corresponding authorship