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: Assistant Professor William (Billy) Hamilton, The Brickman group, First author of Nature paper: Hamilton, W.B., Mosesson, Y., Monteiro, R.S., Emdal, K.B., Knudsen, T.E., Francavilla, C., Barkai, N., Olsen, J.V. and Brickman, J.M. (2019). Dynamic lineage priming is driven via direct enhancer regulation by ERK.Nature, doi: 10.1038/s41586-019-1732-z.
How are distinct cellular identities established in development? How are time and space measured? These are some of the most fundamental questions in developmental biology. My work aims to understand how external signals are interpreted by cells and how they convert these signals into precisely timed responses, in what can be a very noisy environment. Billy has been studying this process at DanStem for approximately 7 years and has uncovered that the framework to choose between self-renewal and differentiation, i.e. the gene-regulatory networks that underpin these choices, are hardwired into stem cells. These regulatory networks are interdependent and rely on extracellular signalling for dominance to be shifted from one to the other. However, this process is complex and is undoubtedly dependent on a host of intrinsic factors. He now hope to expand his research into the field of protein translation to understand how signalling, cell size and shape, as well as cellular fitness impact on cell identity. This new direction will be interdisciplinary, facilitated by the strong theoretical and experimental interactions he gained as a member of StemPhys.
Billy obtained his PhD at the Edinburgh University in the labs of Tilo Kunath and Mike Tyers, where he worked on defining factors that regulate MAPK signalling in mouse embryonic stem cells. He then joined the Brickman lab in Copenhagen where he expanded upon this to uncover how MAPK signalling regulates transcription and plasticity during early stem cell differentiation.
In The Spotlight: Postdoctoral Fellow Martti Maimets was awarded first place poster at the conference 'Intestinal Organoids - from stem cells to metabolism and microbiome interactions', September 29 -October 2, 2019.
The conference brought together world-leading scientists across several research fields to discuss how new technologies including the versatile organoid culture system can provide important knowledge about epithelial cell fate decisions, function and interplay with the microbiota.
The intestine plays essential roles in controlling our metabolism by nutrient uptake, hormone secretion and facilitation of symbiosis with the commensal microbiota. Understanding the complex roles of the epithelium in these processes has proven a great challenge – but a challenge that will provide insights into disease mechanisms and potentially new and improved treatment options.
Martti has been immersed with the biology of organoids since 2010 when he joined the laboratory of professor Rob Coppes in Groningen, the Netherlands as a PhD candidate with the aim of investigating the potential use of salivary gland stem cells in regenerative medicine. By developing conditions for the growth of salivary gland organoids, he identified Wnt/β-catenin signalling pathway as a key driver for adult salivary gland stem cells and demonstrated that the activation of this pathway allows extensive in vitro expansion of these cells. Conducting these studies sparked his interest in the driving force of microenvironment in stem cell biology. To further pursue this topic, he joined the lab of Associate Professor Kim Jensen, (BRIC/DanStem) in Copenhagen, Denmark. During his three years as a postdoc they have collected evidence on how intestinal mesenchymal cells guide epithelial regionalisation during development.
In The Spotlight: PhD student Iris Unterweger, Ober group, was awarded a Boehringer Ingelheim Travel Grant for participation in the “Embryology: Concepts and Techniques in Modern Developmental Biology” summer course at the Marine Biological Laboratory (Woods Hole, USA).
This summer, Iris had the opportunity to attend the six-week laboratory and lecture Embryology course at the Marine Biological Laboratory (MBL) in Woods Hole, Massachusetts, USA. Beside the BIT grant, Iris received a “John & Madleine Trinkaus Endowed Scholarship” and a “Company of Biologists Ltd Scholarship” via the MBL. She applied to this course with the goal of getting in depth knowledge of fundamental principles and mechanisms within the field of embryonic development. “Now looking back, it was so much more than I had expected” says Iris. Besides the daily lectures and the opportunity to get hands-on experience with a wide variety of embryos, encompassing both classic and emerging model organisms, such as butterflies, the atmosphere is very inspiring. Late night experiments, thinking outside the box and informal discussions with both students and faculty, for instance about terminology or the future use of CRISPR made this course absolutely unique.
Iris is educated as a molecular biologist, and completed her Master thesis at the Max-Delbrueck Center for Molecular Medicine (Berlin) before joining DanStem in 2017 as a PhD student in the Ober group. She is interested in how organs form, and currently, her research focuses on understanding the potential of hepatic progenitor cells and their individual contributions to a functional organ.
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: 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: 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, committing 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