Junior Investigator in the Spotlight
With this page, we recognize and appreciate junior investigators who have demonstrated exceptional achievements. Each month one will be in the spotlight where her/his outstanding accomplishments will be highlighted.
In The Spotlight: Postdoctoral Fellow, Jordi Guiu, The Jensen group, First author of Nature paper: Guiu, J., Hannezo, E., Yui, S., Demharter, S., Ulyanchenko, S., Maimets, M., Jørgensen, A., Perlman, S., Lundvall, L., Mamsen, L.S., Larsen, A., Olesen, R.H., Andersen, C.Y., Thuesen, L.L., Hare, K.J., Pers, T.H., Khodosevich, K., Simons, B.D., Jensen, K.B. (2019). Tracing the origin of adult intestinal stem cells. Nature, doi: 10.1038/s41586-019-1212-5.
Cells in tissues are organised hierarchically with a stem cell on top producing their progeny. Importantly during colorectal cancer and intestinal injury this hierarchical behaviour is broken and seemingly differentiated cells might behave as stem cells. Recent work from Jordi Guiu as part of Kim B. Jensen group published in Nature shows that cells in fetal intestine are organised in a flat unhierarchical fashion, thus there is not a designated destiny for cells. Instead all them are equal and have the same probability to become adult intestinal stem cells in vivo. These findings provide a direct link between the observed plasticity and cellular reprogramming of differentiating cells in adult tissue following damage, revealing that stem cell identity is an induced rather than a hardwired property.
Jordi Guiu did his PhD in Anna Bigas laboratory (Barcelona) were he focused on the genetic circuitry that controls the establishment of hematopoietic stem cells during development. Then he joined Kim Jensen lab as a postdoc, were he obtained a Marie Curie fellowship to study the specification of intestinal stem cells during development.
In The Spotlight: Postdoctoral Fellow, Rita Soares Monteiro, The Brickman group, awarded Lundbeck Foundation Postdoctoral Fellowship. Project title: Cell cycle dynamics and regulation by ERK signalling in mouse embryonic stem cells
In this project Rita is aiming to understand how differentiation is linked to proliferation during early embryonic development. 'We will investigate this question, focusing on how the ERK pathway is coupled to the cell cycle in embryonic stem cell (ESC) differentiation' says Rita. A major goal of this project is to monitor both ERK signalling and cell cycle progression alongside mathematical modeling to decipher how signals dynamically regulate lineage choice and cell cycle phase. The outcomes of this project will provide new insights into the relationship between cell cycle regulation and differentiation while revealing the importance of interdisciplinary studies to achieve an integrative understanding of development.
Rita did her bachelors and masters in Evolutionary and Developmental Biology at the Faculty of Sciences of the University of Lisbon and obtained her Ph.D. degree at the University College London working at the lab of Professor Jim Smith, the Francis Crick Institute. During her Ph.D., she studied the regulation of early cell fate determination in amphibian embryos and the role of tissue-specific transcription factors during this process.
In The Spotlight: Assistant Professor Pia Nyeng, First Author of Developmental Cell paper: Nyeng, P., Heilmann, S., Löf-Öhlin, Z.M., Pettersson, N.F., Hermann, F.M., Reynolds, A.B., Semb, H.(2019).p120ctn-Mediated Organ Patterning Precedes and Determines Pancreatic Progenitor Fate.Developmental Cell, 49, 1-17, doi: 10.1016/j.devcel.2019.02.005.
Pia Nyeng studied biology at the University of Copenhagen (Denmark). She did her PhD in Jan Jensen’s group at University of Colorado in Denver (USA) studying FGF-regulation of endodermal organ development. After a short postdoc at Cleveland Clinic in Ohio (USA) she joined Henrik Semb’s group at Lund University (Sweden) as a postdoc. Here she generated new methods for live imaging of pancreatic organotypic cultures and initiated her studies on regulation of pancreas morphogenesis and cell differentiation.
Since the start of Danstem in 2011, Pia has been part of the Semb research group as a postdoctoral researcher and later as an Assistant Professor. Pia’s work at Danstem was supported by a 3-year postdoctoral fellowship from JDRF. Pia is now looking forward to pursue an independent career at the Department of Science and Environment at Roskilde University.
An interview with Pia
In The Spotlight: Postdoctoral Fellow, Patrick Anders Aldrin Kirk, The Kirkeby group, awarded Lundbeck Foundation Postdoctoral Fellowship. Project title: Elucidating the role of lncRNAs in human neural subtype specification using paired CRISPR knockout libraries and single cell RNAseq
Patrick's project aims at uncovering the functional role of long non-coding RNAs (lncRNA) in neural subtype specification during embryonic development. This will be done by developing a comprehensive paired CRISPR library for knockout of lncRNA that are found within the CNS during early development. Elucidation of the fictional role of these lncRNAs by CRISPR knockout on neural cell specification will then be assessed in a microfluidics based In vitro model of the developing human brain.
Patrick obtained his PhD in neurobiology from Lund University in Sweden. His research focuses on combining gene and cell therapy approaches for neurodegenerative disorders, which also included development of novel viral vectors. Another part of his research is also focuses on understanding neuronal function and connectivity in both the healthy and diseased brain, using chemogenetics. His current research interests focus mainly on understanding developmental cues necessary for neuronal subtype specification during development. Patrick hopes to use this knowledge to further investigate future cell therapy approaches within the brain.
In The Spotlight: Postdoctoral Fellow, Paul Riccio, The Semb group, awarded Marie Sklodowska-Curie Actions Postdoctoral Fellowship. Project title: Using the precision mouse genetic tool MADM to elucidate the role of EGFR in directing beta cell differentiation and pancreatic morphogenesis
Succesfull clinical trials of islet transplantation have invigorated the diabetes research community to pursue cell replacement therapies as an eventual cure. These trials relied upon rare human donor tissue. If we can reliably manufacture insulin-producing beta cells from stem cells, many more patients will be able to achieve insulin independence. The Semb group recently showed the EGFR signaling pathway modulates apical polarity in early endocrine progenitors, commiting them to beta differentiation. Paul will use his expertise in the cutting edge genetic tool, Mosaic Analysis with Double Markers to determine why only a portion of these progenitors execute beta differentiation, knowledge key to replicating this process with human stem cells.
Paul has a long-standing interest in how organs like the pancreas form tubes. During his predoctoral training at Columbia University in New York he showed that Ret-expressing tip cells in the kidney undergo competitive cell rearrangements to sculpt the renal collecting system. He will continue to study the dynamics of progenitor cells during tube formation in the pancreas, but also hopes to understand how these morphogenetic events are coordinated with and influence the differentiation processes he will examine during the Marie-Sklodowska Curie Actions Fellowship.
In the Spotlight: Assistant Professor and Translational Scientist Anant Mamidi, First author of Nature paper: 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 progenitors. Nature, doi: 10.1038/s41586-018-0762-2
Incredible progress has been made since the discovery of Insulin almost 100 years ago in terms of disease mechanisms and alternative treatment approaches. This is the stem cell era and significant progress has been made in implementing cell therapies for treating various chronic diseases including diabetes. It is crucial to understand the basic molecular mechanisms behind organ development, In order to achieve a robust and efficient cell differentiation to obtain the right cells in vitro for cell therapy.
Recent work by Anant Mamidi as part of Semb research group uncovered the cascade of molecular events that occur within and around the pancreatic progenitor cells and are responsible for dictating cell fate decisions towards endocrine lineage including insulin expressing beta cells. This work is very important in creating a road map that can be eventually useful in making islet like insulin producing cells in vitro for future cell therapies.
Anant Mamidi obtained his Masters in Microbiology from India and PhD in developmental biology from University of Padova, Italy. He worked as a post-doc and now as Assistant Professor at DanStem since its start in 2011. Anant is continuing to pursue his interest in translational aspects of stem cell research and hopes to contribute in advancement of cell therapy for diabetes patients.
An interview with Anant