Team

Adrenergic signaling in the heart:
Beta-adrenergic receptors are a subclass of G protein-coupled receptors which play a crucial role in the neurohormonal regulation of cardiovascular functions. Activation of these receptors is the strongest mechanism to increase cardiac frequency and contractility. However, sustained activation of b-adrenergic receptors contributes to the development of cardiac disease. We currently study b-adrenergic receptor signaling, search for novel downstream targets and study the impact of receptor polymorphisms on ligand-induced conformational changes of the receptor protein.

Role of microRNAs in cardiac health and disease:
MicroRNAs control diverse biological processes including major signaling pathways by regulating the expression of complementary target mRNAs. Although MicroRNAs were recently implicated in the regulation of diverse cardiac functions in a series of elegant genetic studies, detailed molecular mechanisms for microRNAs in disease pathways in vivo are poorly understood. We have identified several candidate microRNAs, which are severely deregulated in cardiac disease and established techniques for detecting, quantifying and manipulating microRNA expression.

Ubiquitin-Proteasome System:
Another research focus at the Institute of Pharmacology and Toxicology is the role of the ubiquitin-proteasome system. The laboratory of Dr. Antonio Sarikas uses interdisciplinary approaches that include modern methods of molecular biology, protein biochemistry and mouse genetics to study the regulation of signaling pathways by the ubiquitin-proteasome system. Please also see www.sarikaslab.de.

www.ipt.med.tu-muenchen.de/index.php?id=24&L=1

Our group is exploring how different immune cell signals contribute to the development of different B cell malignancies and how metabolic cues support the escape of B cell intrinsic checkpoint that usually prevent transformation.  The current focuses of our laboratory are on the transformation of chronic lymphocytic leukemia to an aggressive lymphoma as well as the plasma cell disorder multiple myeloma. Mouse models recapitulating major mechanisms of the human diseases play an important role in our work. Using transgenic mouse lines with the Cre-loxP technology, we investigate the influence of several (signalling) factors on the development and the progression of diseases in these animal models.

CLL and Richter’s Transformation:
We have established a model to mimic the transformation of CLL to an aggressive lymphoma by additional oncogene activation. We have observed that acute oncogene activation in CLL cells induces cell death in the vast majority of CLL cells (Ecker et al, Nat. Comm. 2021). However, some cells survive and then outgrow the initial tumor and show several features of Richter cells. We now aim to use this model to understand which mechanism support the survival of the cells giving rise to the aggressive lymphoma and verify these in human samples. Understanding those mechanisms may help to prevent or treat the aggressive Richter lymphoma, which has a very poor clinical outcome.

CLL and drug resistance:
Another focus of our group is to understand how different signals from the microenvironment support the expansion of CLL cells despite the highly effective treatment with the BTK inhibitor ibrutinib or the BCL2 inhibitor venetoclax. We investigate strategies to prevent these interactions and to breach the strong immunosuppressive character of CLL cells, which then are tested in combination with immunotherapy (CAR T cells and checkpoint inhibition) in CLL. 

Multiple Myeloma:
We have generated a novel mouse model that reflects the human plasma cell disorder multiple myeloma in several ways. To gain insight into the pathogenesis of this deadly disease, we aim to analyse which factors contribute to the disease evolution in our model and compare it with data of human myeloma samples.

https://www.translatum.tum.de/translatum/forschungsgruppen-1/maike-buchner-immunzellensignalisierung-bei-chronischer-lymphatischer-leukaemie/

The Portugues lab studies how the brain generates behavior. This requires understanding what features of the environment are behaviorally relevant, how the brain is tuned to respond to them, what mechanisms are in place to select appropriate actions and how learning can lead to improved interactions between the animal and its environment. We mainly use the larval zebrafish, a small vertebrate, as a model organism.
We use a highly multidisciplinary approach that uses behavior, functional calcium imaging (both 2-photon and light-sheet microscopy), optogenetics, electrophysiology, computational and theoretical methods to dissect these questions across scales that range from a single neuron to the 100,000 neurons that comprise the whole brain of zebrafish larvae.

Selected publications:
Markov DA, Petrucco L, Kist AM, Portugues, R (2021). “A cerebellar internal model calibrates a feedback controller involved in sensorimotor control.” Nature Communications, in press.

Yildizoglu T, Riegler C, Fitzgerald JE*, Portugues R* (2020). “A Neural Representation of Naturalistic Motion-Guided Behavior in the Zebrafish Brain.” Current Biology 30 (12), 2321-2333.

Dragomir EI, Štih V, Portugues R (2020). “Evidence accumulation during a sensorimotor decision task revealed by whole-brain imaging”. Nature Neuroscience. 2020; (23) 85-93.

Kist AM, Portugues R (2019). “Optomotor swimming in larval zebrafish is sriven by global whole-field visual motion and local light-dark transitions.” Cell Reports, 29 (3), 659-670.

Štih V*, Petrucco L*, Kist AM, Portugues R (2019). “Stytra: An open-source, integrated system for stimulation, tracking and closed-loop behavioral experiments”. PLOS Computational Biology, 15 (4), e1006699.

Knogler LD, Kist AM, Portugues R (2019). "Motor context dominates output from purkinje cell functional regions during reflexive visuomotor behaviours". eLife. 2019: e42138.

Knogler LD, Markov AD, Dragomir EI, Štih V, Portugues R (2017). "Sensorimotor representations in cerebellar granule cells in larval zebrafish are dense, spatially organized, and non-temporally patterned". Current Biology. 2017; 27(9): 1288-1302.

Oteiza P, Odstrcil I, Lauder G, Portugues R, Engert F(2017). "A novel mechanism for mechanosensory-based rheotaxis in larval zebrafish". Nature. 2017: 547(7664): 445-448.

Portugues R, Feierstein CE, Engert F, Orger MB (2014). "Whole-brain activity maps reveal stereotyped, distributed networks for visuomotor behavior". Neuron. 2014; 81(6): 1328-1343.

Severi KE*, Portugues R*#, Marques JC, O'Malley DM, Orger MB, Engert F# (2014). “Neural control and modulation of swimming speed in the larval zebrafish.” Neuron 83 (3), 692-707.

Ahrens MB, Li JM, Orger MB, Robson DN, Schier AF, Engert F, Portugues R (2012). Brain-wide neuronal dynamics during motor adaptation in zebrafish. Nature 485: 471-477.