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Hollfelder Group

Postdoc

Joined the lab: October 2014
 

Background and Current Projects: I was trained as a biochemist during my undergraduate and master studies. Subsequently, I specialised in stem cell biology and early embryonic development during my PhD at the University of Cambridge. My work was focussed on how pluripotency – a cell’s ability to differentiate into any cell of the body – is established, maintained and executed. I found pluripotency to be of particular excitement as it offers the starting point for the treatment of disease‑induced loss of cells (e.g. diabetes or neurodegenerative diseases). Yet, many mechanisms of how pluripotency is regulated remain elusive. One challenge is that cells are conventionally grown on two‑dimensional plastic dishes. Fairly easy and robust, but it fails to incorporate the in vivo (in the organism) tissue architecture and biomechanical signals. To this end, I developed a microfluidic‑based technology to encapsulate cells into biomimetic three‑dimensional hydrogel scaffolds that enabled the study of biomechanical forces (such as compression) that would otherwise be neglected under conventional cell culture conditions. With this collaborative effort between the Department of Biochemistry and the Cambridge Stem Cell Institute, my research identified a compression‑regulated mechanism that enhances the maintenance of the pluripotent state (Kohler et al., in preparation). Pluripotency is an evolutionary conserved feature of mammalian development and we have already shown our system’s versatility with regards to different cell types and species (Schindler, Siriwardena, Kohler et al., 2021; Cordero-Espinoza et al., 2021; Munger, Kohler, Slatery et al., submitted). Therefore, during the next steps I will be investigating pluripotency across species with special attention to endangered species. Understanding the species‑specific regulatory mechanism of pluripotency might assist conservation efforts and might ultimately refine our understanding of human development in health and disease.

Interests: I take photos and run a lot. Happy amongst specialty coffee and (bio)diversity!

 

Publications 

[4] Schindler, M.*, Siriwardena, D.*, Kohler, T.N.*, Ellermann, A.L., Slatery, E., Munger, C., Hollfelder, F., and Boroviak, T.E. (2021). “Agarose microgel culture delineates lumenogenesis in naive and primed human pluripotent stem cells”. Stem Cell Reports 16, 1347-1362. Link

[3] Cordero-Espinoza, L., Dowbaj, A.M., Kohler, T.N., Strauss, B., Sarlidou, O., Belenguer, G., Pacini, C., Martins, N.P., Dobie, R., Wilson-Kanamori, J.R., et al. (2021). “Dynamic cell contacts between periportal mesenchyme and ductal epithelium act as a rheostat for liver cell proliferation”. Cell Stem Cell, S1934-5909(21)00287-3.   Link. 

[2] Salmen, F., de Jonghe, J., Kaminski, T., Alemany, A., Parada, G., Verity-Legg, J., Yanagida, A., Kohler, T.N., Battich, N., van den Brekel, F., Ellermann, A.L., Martinez Arias, A., Nichols, J., Hemberg, M., Hollfelder, F., van Oudenaarden, A. (2021) “Droplet-based Single-cell Total RNA-seq Reveals Differential Non-Coding Expression and Splicing Patterns during Mouse Development”. bioRxiv.  Link 

[1] Mulas, C., Hodgson, A.C., Kohler, T.N., Agley, C.C., Humphreys, P., Kleine-Bruggeney, H., Hollfelder, F., Smith, A., and Chalut, K.J. (2020). “Microfluidic platform for 3D cell culture with live imaging and clone retrieval.” Lab Chip20, 2580-2591. Link

 

Contact Details

email: tnk24@cam.ac.uk

Job Title

Post-doctoral Research Associate