This is the website of the Carlos Ibanez lab at the Karolinska Institute. In this page, we post the latest news from the KI lab. Make sure to visit the different sections of the site for more information. If you were redirected to this page from our older address, please bookmark the new address carlosibanezlab.se for future use.
Work at Carlos Ibanez laboratory focuses on understanding the functions and signaling mechanisms of growth factors and their receptors in neural development and injury responses and metabolic regulation, for the development of better therapies to diseases of the nervous system and metabolic disorders.
Carlos Ibanez is Professor of Neuroscience at the Karolinska Institute in Stockholm, Sweden.
Postdoctoral fellows are currently being recruited to the laboratory to advance research on growth factor receptor signaling and function in neurodevelopment and neural injury. We are seeking talented, innovative and enthusiastic researchers with a PhD awarded within the last 5 years. Candidates with expertise in i) molecular and cellular neurobiology, neurodevelopment or ii) molecular and cellular endocrinology, metabolic research and iii) mouse genetics are encouraged to apply.
Applications, including CV, list of publications and statement of future interests should be sent to Prof. Carlos Ibanez (). Applicants should arrange to have at least two confidential letters of reference sent independently by referees to this email address.
Funding is available for an initial period of 2 to 3 years, starting any time during 2014.
Deadline for application is May 10, 2014
Diabetologia has now published online our latest paper describing differential actions of activins A and B and Smad proteins 2 and 3 on the regulation of insulin secretion by pancreatic beta cells (Wu et al., 2013).
Glucose-stimulated insulin secretion (GSIS) from pancreatic beta-cells is regulated by paracrine factors whose identity and mechanisms of action are incompletely understood. Activins are expressed in pancreatic islets and have been implicated in the regulation of GSIS. Activins A and B signal through a common set of intracellular components, but it is unclear whether they display similar or distinct functions in glucose homeostasis. Glucose homeostatic responses were examined in mice lacking activin B and in pancreatic islets derived from these mutants. The ability of activins A and B to regulate downstream signalling, ATP production and GSIS in islets and in beta-cells was compared. Mice lacking activin-B displayed elevated serum insulin levels and glucose-stimulated insulin release. Injection of a soluble activin B antagonist phenocopied these changes in wild type mice. Isolated pancreatic islets from mutant mice showed enhanced GSIS which could be rescued by exogenous activin B. Activin B negatively regulated GSIS and ATP production in wild type islets, while activin-A displayed opposite effects. The downstream mediator Smad3 responded preferentially to activin B in pancreatic islets and beta-cells, while Smad2 showed preference for activin A, indicating distinct signalling effects of the two activins. In line with this, overexpression of Smad3, but not Smad2, decreased GSIS in pancreatic islets. These results reveal a tug-of-war between activin ligands in the regulation of insulin secretion by beta-cells and suggest that manipulation of activin signalling could be a useful strategy for the control of glucose homeostasis in diabetes and metabolic disease.
Read the full article HERE.
The European Research Council (ERC) has announced that Carlos Ibanez is among the winners of the 2013 Advanced Grant competition. At 2.5 million Euros –for a 5 year project– the ERC Advanced Grant has become one of the most prestigious research awards in Europe. In this round, a total of 284 researchers were awarded from over 2,400 applicants, a success rate of 11.8%.
Lilian Kisiswa obtained a PhD in 2011 in Visual Neursocience at Cardiff University, UK, under the direction of Prof. James E Morgan. Her PhD thesis was entitled “The role of inhibitor of apoptosis (IAPs) in retinal ganglion cell death and dendrite remodelling“. She then did postdoctoral studies at the Department of Molecular Biosciences, School of Biosciences, Cardiff University, under the direction of Prof. Alun M Davies. Her postdoctoral work on reverse signaling by TNF ligands was recently published in Nature Neuroscience. Lilian will join the Stockholm p75 team in August 2013 to investigate the interplay between RIP2 and RhoGDI in the control of axon growth and degeneration by p75NTR and its ligands.
Diana Fernandez Suarez obtained her PhD in 2012 at the Center for Applied Medical Research University of Navarra, Pamplona, Spain, under the direction of Drs.Rafael Franco and Maria Soledad Aymerich. Her PhD thesis was dedicated to anatomical and funcitonal studies of the globus pallidus after manipulation of the endocanabinoid system in animal models of Parkinson’s disease. She performed postdoctoral work at the same laboratory during the past year. Diana will join the KI GDNF team in August 2013 to investigate adult functions of GFRa1 signaling in the healthy and diseased brain.
Work at our laboratory focuses on understanding the functions and signaling mechanisms of neuronal growth factors in neural development, injury responses and metabolic regulation, for the development of better therapies to diseases of the nervous system and metabolism.
Postdoctoral fellows are currently being recruited to the laboratory. We are seeking talented, innovative and enthusiastic researchers with a PhD awarded within the last 10 years. Candidates with expertise in neurobiology, metabolism and mouse genetics are encouraged to apply.
Applications, including CV, list of publications and statement of future interests should be sent to Prof. Carlos Ibanez . Applicants should arrange to have at least two confidential letters of reference sent independently by referees to this email address.
Funding is available for an initial period of 2 to 3 years, starting any time during 2013.
Deadline for application is March 31, 2013.
Cold Spring Harbour Perspectives in Biology has published Carlos Ibanez’s review on the structure and physiology of the RET receptor tyrosine kinase as part of their collection of reviews on receptor tyrosine kinases. RET, GDNF family ligands, and GFRα coreceptors activate signaling pathways involved in kidney and nervous system development. RET mutations cause Hirschsprung’s disease and at least four cancers. Read the full paper HERE.
Cell Reports publishes today our latest paper describing a structure-function map of the death domain of the p75 neurotrophin receptor (Charalampopoulos et al. 2012)
Structural determinants underlying signaling specificity in the tumor necrosis factor receptor superfamily (TNFRSF) are poorly characterized and it is unclear whether different signaling outputs can be genetically dissociated. The p75 neurotrophin receptor (p75NTR), also known as TNFRSF16, is a key regulator of trophic and injury responses in the nervous system. In this paper, we describe a genetic approach to dissect p75NTR signaling and decipher its underlying logic. Structural determinants important for regulation of cell death, NF-kB and RhoA pathways were identified in the p75NTR death domain. Pro-apoptotic and pro-survival pathways mapped onto non-overlapping epitopes, demonstrating that different signaling outputs can be genetically separated in p75NTR. Dissociation of JNK and caspase-3 activities indicated that JNK is necessary but not sufficient for p75NTR-mediated cell death. RIP2 recruitment and RhoGDI release were mechanistically linked, indicating that competition for DD binding underlies cross-talk between NF-kB and RhoA pathways in p75NTR signaling. These results provide new insights into the logic of p75NTR signaling and pave the way for a genetic dissection of p75NTR function and physiology.
Read the full paper HERE.
The Knut and Alice Wallenberg Foundation has today appointed Carlos Ibanez as a Wallenberg Scholar. The award includes a research grant of 15 million Swedish crowns over 5 years. Quote from the Foundation’s website: “The Foundation’s purpose is to support Swedish research and thereby strengthen Sweden as a research nation. Since 2009, we have appointed a total of 46 Wallenberg Scholars. The appointed researchers all belong to the international research forefornt in all areas of science, with an emphasis on medicine and the natural sciences, says Peter Wallenberg Jr., vice chairman of the Knut and Alice Wallenberg Foundation.” Read the text of the announcement (in Swedish) HERE and press release from Karolinska Institute HERE.
The Journal of Neuroscience publishes today our paper on the role of the GDNF receptor GFRa1 in the main olfactory system (Marks et al. 2012). In this work, we investigated the consequences of GFRα1 deficiency for mouse olfactory system development and function.
GDNF and its receptor GFRα1 are prominently expressed in the olfactory epithelium (OE) and olfactory bulb (OB), but their importance for olfactory system development has been unknown. In the OE, we found that GFRα1 was expressed in basal precursors, immature olfactory sensory neurons (OSNs), and olfactory ensheathing cells (OECs), but was excluded from mature OSNs. The OE of newborn Gfra1 knock-out mice was thinner and contained fewer OSNs, but more dividing precursors, suggesting deficient neurogenesis. Immature OSN axon bundles were enlarged and associated OECs increased, indicating impaired migration of OECs and OSN axons. In the OB, GFRα1 was expressed in immature OSN axons and OECs of the nerve layer, as well as mitral and tufted cells, but was excluded from GABAergic interneurons. In newborn knock-outs, the nerve layer was dramatically reduced, exhibiting fewer axons and OECs. Bulbs were smaller and presented fewer and disorganized glomeruli and a significant reduction in mitral cells. Numbers of tyrosine hydroxylase-, calbindin-, and calretinin-expressing interneurons were also reduced in newborn mice lacking Gfra1. At birth, the OE and OB of Gdnf knock-out mice displayed comparable phenotypes. Similar deficits were also found in adult heterozygous Gfra1+/− mutants, which in addition displayed diminished responses in behavioral tests of olfactory function. We conclude that GFRα1 is critical for the development and function of the main olfactory system, contributing to the development and allocation of all major classes of neurons and glial cells.
Read the full paper HERE.
PhD student Carolyn Marks nailed her thesis at the KI library this week. Tradition obliges, and the golden nail went into the wooden slab one more time.
The event marks the final count-down for her thesis defense, to take place on December 7. Attracted by the prospect of champagne and refreshments, fellow lab mates joined in for the occassion.
Photograph by postdoc fellow Tingqing Guo.