Mathias Treier
Charité – Universitätsmedizin Berlin
Max-Delbrück Center for Molecular Medicine (MDC)
AG Genetics of Metabolic & Reproductive Disorders
Tel: +49 30 9406 3460
E-Mail: mathias.treier@mdc-berlin.de
Genetics of metabolic and reproductive disorders
Murine blastocyst stained with an antibody detecting Sall4
The specification of cell types during organ development has been studied intensively over the last decade. The future challenge will be to unravel how these different cell types function in a concerted action within an organ so that each organ can fulfill its physiological task within an organism. Ultimately the goal is to understand how mammalian physiology is orchestrated to allow an organism to survive in a changing metabolic environment.
We are employing mouse genetics to study various aspects of mammalian physiology, from the single cell stage to the complex interplay between organs that allow an organism to maintain energy homeostasis.
Stem/progenitor cell populations constitute the basic building units from which organs and whole organisms are created. We have identified with the transcriptional regulator, SALL4 a key player that is required to maintain the pluripotency state of embryonic stem cells. SALL4 is highly expressed in the inner cell mass (ICM) of the blastocyst which will give rise to the embryo proper and the primitive endoderm (figure 1 Schematic drawing of a cilium transmitting an extra-cellular signal to the nucleus). We are currently employing omics technology to understand the regulation and function of this central player in stem cell biology.
At the organ level we are interested how cells are able to react to changes in their microenvironment. Recently, the cilium has emerged as a crucial sensor of growth factors and physiological parameters in body fluids. With the GLIS family of transcriptional regulators, we have identified molecular players that are involved in transmitting the signal from the cilium to the nucleus allowing i.e. kidney cells to respond to changes in their surrounding. We are now investigating at the molecular level how cilia signal transmission is regulated through post-translational modifications. Understanding cilia signaling in general will have implications for many human ciliopathies, i.e. Bardet-Biedel syndrome, that are caused by malfunctioning of this organelle.
Illumination of the BSX neuronal network in the hypothalamus
The ultimate goal for any living organism is to maintain energy homeostasis in its quest to survive. We are particular interested in the neuronal circuits of the central nervous system (CNS) that are regulating energy homeostasis. We have identified with the brain-specific homeobox protein BSX an essential player in the regulation of food intake and locomotor activity, which are the two main components that determine energy balance. We are currently investigating how higher brain centers integrate peripheral signals for satiety and hunger to regulate our drive to eat.
Reproductive fitness is central for any species to adapt to changing environmental conditions. Sexual reproduction allows the fast reshuffling of genetic information but requires the maintenance of male and female individuals within a species. We have recently uncovered the underling molecular mechanism of sexual identity in mammals unraveling an unexpected plasticity that we now try to understand at the epigenetic level.Transcriptional regulators will continue to be at center stage of our investigations. In particular, we have started to look how metabolic changes influence the epigenetic landscape to modulate transcriptional responses to environmental cues. With a series of mouse models for human diseases that we have created over the last years, we are now in a position to dissect even complicated physiological questions at the organismal level.
Curriculum vitae
Since 2011 W3 Professorship at Charité – Universitätsmedizin Berlin, Head of Research Group “Genetics of Metabolic & Reproductive Disorders”, MDC
2010 - 2011 W3 Professorship and Director of the Institute for Molecular Endocrinology, University of Cologne, Germany
2000 - 2009 Independent Group Leader, Developmental Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany
1995 – 1999 Postdoctorate, (Advisor: Prof. M. G. Rosenfeld) Howard Hughes Medical Institute, University of California, San Diego, USA,
1991 - 1994 Ph.D. thesis in Molecular Biology (Advisors: Prof. T. Graf andProf. D. Bohmann), European Molecular Biology Laboratory, (EMBL) and Universität Heidelberg, Germany
1984 - 1990 Studies in Biochemistry, Diploma work (Advisor: Prof. S. Jentsch) Universität Tübingen, Germany
Research fields
Our group conducts research on:
• Mouse models for human diseases
• Epigenetic regulation of mammalian physiology
• Transcriptional regulation of stem cell populations in organ development
Selected Publications
Uhlenhaut N, Jakob S, Anlag K, Eisenberger T, Sekido R, Kress J, Treier AC, Klugmann C, Klasen C, Holter N, Riethmacher D, Schütz G, Cooney A, Lovell-Badge R & Treier M (2009). Somatic sex reprogramming of adult ovaries to testes by FOXL2 ablation.
Cell 139:1130-1142.
Coldren C, Lai Z, Shragg P, Rossi E, Zuffardi O, Mattina T, Ivy D, Curfs L, Mattson S, Riley E, Treier M & Grossfeld P (2009) Comparative genomic hybrdization mapping suggests a role for BSX and Neurogranin in neurocognitive and behavioral defects in the 11q terminal deletion disorder (Jacobsen syndrome)
Neurogenetics 10(2):89-95
Attanasio M, Uhlenhaut NH, Sousa V, O’Toole JF, Otto E, Anlag K, Klugmann C, Treier AC, Helou J, Sayer JA, Seelow D, Nürnberg G, Becker C, Chudley AE, Nürnberg P, Hildebrandt F & Treier M (2007) Loss of GLIS2 causes nephronophthisis in humans and mice by increased apoptosis and fibrosis.
Nat. Genetics 39:1018-1024.
Sakkou M., Wiedmer, P, Anlag, K, Hamm, A., Seuntjens, E., Ettwiller, L.,Tschop, M & Treier M (2007) A Role for Brain-Specific Homeobox Factor Bsx in the Control of Hyperphagia and Locomotory Behavior
Cell Metabolism, 5:450-463
Elling, U., Klasen, C., Eisenberger, T., Anlag, K. & Treier, M. (2006)
Murine inner cell mass derived lineages depend on Sall4 function.
PNAS 103(44), 16319-24.
Müller T, Anlag K, Wildner H, Britsch S, Treier M & Birchmeier C (2005)
The bHLH factor Olig3 coordinates the specification of dorsal neurons in the spinal cord
Genes & Dev.19:733-743 equal contribution of both labs.
Schmidt D, Ovitt CE, Anlag K, Fehsenfeld S, Gredsted L, Treier AC & Treier M (2004) The murine winged-helix transcription factor Foxl2 is required for granulosa cell differentiation and ovary maintenance.
Development 131(4):933-42.
Treier M, Gleiberman AS, O'Connell SM, Szeto DP, McMahon JA, McMahon AP & Rosenfeld MG (1998)
Multistep signaling requirements for pituitary organogenesis in vivo
Genes & Dev 12:1691-1704
Treier M, Bohmann D & Mlodzik M (1995)
JUN cooperates with the ETS domain protein Pointed to induce photoreceptor R7 fate in the Drosophila eye
Cell Vol. 83, pp. 753-760
Treier M, Staszewski LM & Bohmann D (1994)
Ubiquitin-dependent c-Jun degradation in vivo is mediated by the delta-domain.
Cell 78:787-798.