“My research combines mouse genetics, detailed physiologic and hemodynamic measurements, and animal models of human disease, including stroke, atherosclerosis, and diabetes. My current work focuses on the role of Akt-eNOS-cGMP axis in cerebrovascular dysfunction. My publications demonstrated that mice that carry specific S1177D mutation in eNOS gene are protected against stroke, and that they show less obesity and metabolic abnormalities on high fat diet. We show that unphosphorylatable eNOS impairs vascular reactivity to nitric oxide and is associated with incomplete reperfusion, larger infarct size, and worse metabolic profile, suggesting that S1177 eNOS is protective in ischemic stroke. We have found that increased phosphorylation of eNOS on serine 1177 normalized vascular abnormalities in type 2 diabetic mice and protect them against reperfusion injury. The overall unifying theme behind my work is to apply in vivo physiology and disease models and in vitro vascular reactivity measurements, to genetic models relevant to the NO pathway, such as nNOS, eNOS, iNOS, soluble guanylate cyclase, and C-reactive protein.” - D. Atochin's Research Profile

“We are investigating the molecular and cellular regulation of T cell responses and aim to use this knowledge to understand and improve immunotherapies.

Deep vein thrombosis (DVT) is the leading cause of pulmonary embolism, the leading cause of disability and death worldwide. In addition to direct thromboembolic damage, chronic insufficiencies such as post-thrombotic syndrome (PTS) or chronic thromboembolic pulmonary hypertension (CTEPH) are frequent consequences. The current treatment of acute DVT with anticoagulants and vasoactive drugs limits the further growth of clots that have formed, but cannot prevent re-thrombus formation and long-term complications. The transition from thromboembolic events to chronic disease is essentially caused by persistent inflammation, which leads to delayed thrombus dissolution, fibrosis and damage to the vascular wall.

While the role of innate immune cells in thrombogenesis and thrombolysis has been known for decades, a possible involvement of adaptive immune cells has long been excluded. In a mouse model of venous thrombosis, we were able to show for the first time that so-called effector memory T cells (TEM) infiltrate thrombi and adjacent vein walls, are activated independently of the antigen, and delay the dissolution of the thrombus through mutual stimulation with monocytes (Circ Res 2016) . A fascinating result of our study is that the number of thrombus-infiltrating TEM cells increases with the size of the peripheral TEM pool. This observation suggests a possible connection between the age-dependent increase in circulating TEM cells and the age-dependent increase in long-term complications in DVT patients.” - Becker Lab

“At the Institute for Pharmacology and Clinical Pharmacy, we investigate the mechanisms that underlie the specificity and the spatio-temporal organization of the G protein mediated signal transduction. Specifically, we are investigating both GPCRs and their downstream G proteins, their interaction and activation mechanisms. In addition, we analyze the mechanisms of how the receptors bind to adaptor molecules including G protein-coupled receptor kinases and arrestin. The question of whether and how the membrane potential influences signal transmission via GPCRs is also the subject of our current research. Last but not least, we are experts in generation of transgenic mice expressing FRET-based biosensors, which allows us to perform real-time cAMP imaging in intact tissue.” - Bünemann Lab

“In our department we investigate the neural basis of learning and memory and decision-making processes in rodent models. Here, we aim to understand the role of specific brain areas and neurotransmitter systems as well as the architecture and function of neural circuits and synaptic plasticity mechanisms. Towards this end, we use a wide range of techniques including behavioral pharmacology and behavioral analyses, electrophysiology, viral gene transfer, optogenetics, imaging techniques and anatomical approaches.” - Department of Neurobiology

“In the working group we were able to demonstrate by means of immunohistochemistry that the enzyme NO-GC is very strongly expressed in pericytes. Pericytes are mural cells of the microcirculation, which wrap themselves around the blood vessels by means of finger-like extensions. They are found on capillaries, precapillary arterioles, and postcapillary veins in virtually all tissues. They interact both chemically and physically with the endothelial cells. Pericytes thus stabilize endothelial sprouting and support the maturation of blood vessels. The ability to differentiate into different cell types as multipotent cells, which has been described in the literature so far, is now being questioned. Because of their localization, pericytes play a fundamental role in vascular plasticity, the formation of the blood-brain barrier and capillary permeability. It is therefore assumed that the clinical relevance of the pericytes is very high. The interaction between pericytes and endothelial cells plays an important role in the pathogenesis of various diseases such as diabetic retinopathy, organ fibrosis and cancer growth. Since the role of NO-GC and thus the NO / cGMP-mediated signal cascade in these cells has hardly been investigated, we are concerned with pericyte-mediated processes in the lungs, liver and heart.” - Friebe Lab

“The long-term goal of my research is to reveal the fundamentals of vascular biology in both physiological and pathophysiological settings, and to exploit this newfound knowledge for the detection and treatment of diseases. Innovative animal models and state of the art imaging techniques are essential to achieve this goal. I have been developing and utilizing such imaging techniques - including an in vivo fluorescent protein gene reporter system, intravital multiphoton laser-scanning microscopy and optical frequency domain imaging in collaboration with world-renowned experts at MGH. With these cutting-edge in vivo imaging approaches we have been providing novel insights into the role of host-tumor interaction in angiogenesis, vascular function, tumor growth, and response to treatment.” - D. Fukumura's Research Profile

“We develop optogenetic methods to stimulate identified neurons and to optically measure the amplitude of postsynaptic calcium transients in dendritic spines. Two-photon laser scanning microscopy allows us to perform such optophysiological experiments in intact brain tissue with high spatial and temporal resolution. Using genetically encoded probes, we monitor the activity of single synapses over several hundred stimulations and measure parameters such as synaptic potency and the probability of glutamate release. Optical induction of plasticity at individual, identified synapses allows us to investigate the underlying electrical and biochemical processes in great detail. The connectivity of our brain constantly changes in response to sensory experience (Huber et al., 2012). A central aim of our research is to understand the rules and molecular mechanisms that govern our extraordinary ability to learn and to remember.” - Institute of Synaptic Physiology

"In retinal rods, cGMP is the second messenger that links photon capture by rhodopsin on internal disk membranes to ion channel activity on the plasma membrane. Rhodopsin photoexcitation leads to the hydrolysis of cGMP and subsequent closure of cGMP-gated channels, curtailing the entry of Na+ and Ca2+. During response recovery, retina-specific guanylyl cyclases (retGCs) replenish cGMP, reopen the channels, and restore the influx of cations. To facilitate the recovery, guanylyl cyclase activating proteins (GCAPs) sense the decrease in Ca2+ caused by illumination and greatly stimulate the rate of cGMP synthesis." - C. Makino's Research Profile

“Our institute investigates the role of cAMP and cGMP in heart failure. These ubiquitous second messengers show both negative and protective effects in cardiomyocytes. The outcome of their signals eventually depends on the subcellular compartments where cAMP and cGMP exert their action. For example, beta2-adrenergic receptors localized in the T-tubules of healthy cardiomyocytes can activate cardioprotective mechanisms, whereas in failing myocytes, the same receptors change their location and may exert detrimental effects. We use highly sensitive biosensors and new imaging techniques such as fluorescence resonance energy transfer (FRET) and scanning ion conductance microscopy (SICM) to visualize cAMP and cGMP gradients with high temporal and spatial precision in various subcellular areas of cardiomyocytes. Combined with the analysis of membrane ultrastructure in healthy and failing cells, this information should shed light on the molecular mechanisms of heart failure and help identify new therapeutic strategies.” - Institute of Experimental Cardiovascular Research

“The Department of Pharmacology pursues both basic science projects and projects with the aim to solve medical problems. Basic science projects focus on the analysis of the molecular mechanisms of particular cellular signaling pathways (e.g. G-protein mediated signaling, G-protein-coupled receptors, semaphorin/plexin-system) and on the understanding of particular physiological processes in the mammalian organism. More medically oriented scientific projects deal with the mechanisms of pathophysiological processes and drug actions, in particular in the cardiovascular and metabolic system as well as in cancer with the option to carry the projects to a translational level.” - Department of Pharmacology

“Tumors of all tissues emerge due to the sequential acquisition of genetic alterations, leading to oncogene activation and loss of tumor suppressor functions. Our research focus is on the ErbB/HER family of receptor tyrosine kinases and the DLC family of tumor suppressors and their contribution to cancer cell survival and proliferation, invasive migration, and drug resistance when deregulated. We further have a special interest in understanding how cellular membranes assemble and regulate protein signaling complexes. To address these scientific questions, the lab utilizes advanced biochemical and molecular biology techniques, 2D/3D cell and organoid culture models in combination with state-of-the-art imaging and genome editing approaches.” - Olayioye Lab

“This group investigates the mechanisms of neuronal cell death in the retina to forward the development of novel therapies for retinal diseases. Neurodegenerative diseases are an ever-increasing health concern in the ageing human populations. The retina as an integral part of the central nervous system (CNS) combines easy access with a large number of animal models available for investigations of development, function, and pathology. We use the retina as a model system to investigate neuronal degeneration with a particular focus on photoreceptor cell death and inherited retinal degeneration (RD), diseases grouped under several different clinical terms including Retinitis Pigmentosa (RP), Leber´s Congenital Amaurosis (LCA), and Achromatopsia (ACHM).” - Paquet-Durand Lab

“The research projects of the Raker group focus on cells of monocytic origin. The scientists around Dr. Raker investigate how monocytes are recruited into tissue and ultimately differentiate further. Monocytes are the shapeshifters of immunology with a wide range of possibilities. They can differentiate into a wide variety of phagocytes such as macrophages or dendritic cells or act as immunomodulators themselves. Because of their versatile function, monocytes are often found as initiators of chronic inflammation and autoimmunity.

The group researches how to modulate the recruitment, conversion and differentiation of monocytes. You use mouse models for various immunodermatoses (e.g. scleroderma) and also the examination of sample material from the corresponding patients. The use of a humanized mouse model enables the scientist to test potential intervention strategies on human immune cells.” - Raker Lab

“Since my doctoral and post-doctoral studies, I’ve been working on physiological growth processes and hypoxia-induced gene expression, but I was also examining one of the basic processes in the human body: the Nitric Oxide (NO)/cyclic guanosine monophosphate (cGMP) signal transduction cascade and the effects of cGMP degrading phosphodiesterases (PDEs). This NO/cGMP pathway is a crucial biochemical process responsible for the regulation of cell and organ functions. It transmits the external stimuli the gas Nitric Oxide (NO) over several stations to the inner cell. The key event is binding of NO on the intracellular soluble guanylyl cyclase (sGC) which triggers cGMP formation. The cGMP is the vehicle inside cells then mediating the physiological responses. One of its duties is the regulation of blood vessel tone and blood pressure, but additional effects were and are currently discovered, which makes cGMP an exciting molecule.

In many diseases, this NO/cGMP signal cascade is out of order, and the body is short on cGMP. That´s why Bayer works on the development of agents that influence the cGMP formation: These sGC stimulators and sGC activators can directly bind and activate the sGC without requiring NO. This is a very special mode of action, and a first sGC stimulator – used for treating pulmonary hypertension, is already available on the market. Another agent is in the Phase III clinical trials for the treatment of heart failure. We hope that we can treat even more diseases, like kidney diseases but also very rare diseases, with our sGC stimulators and sGC activators.” - P. Sandner's Scientist Portrait

"With a double degree in Medicine and Pharmacy Harald Schmidt is an international leader in drug discovery and therapy as well as big data for network medicine. He performs high risk/high potential benefit research in areas of major medical need. His multi-national leadership experience in Academia and Industry has led to excellent scientific achievements with high socio-economic impact such as patents and biotech spin-offs. He is a successful entrepreneur, dedicated teacher and team leader and through Rotary International highly engaged in his community.

Harald Schmidt is an MD and pharmacist and has worked in three continents, Europe, USA and Australia in leadership positions both in academia, biotech and industry. His work focusses on drug discovery and repurposing, target validation, biomarkers within the context of personalised and precision medicine." - Maastricht University

“Our key research focus is on the characterization of cellular and molecular mechanisms of pain processing. Fully functional pain perception is essential to protect the human body from harmful influences. In conditions of persistent pain such as inflammation or nerve injury, pain loses its protective functions and may become a disease in its own right. Typical characteristics of persistent pain are increased response to pain stimuli (hyperalgesia), painful perception of usually non-painful stimuli (allodynia) and the development of spontaneous pain without apparent cause. This sensitization of the pain processing system poses a major therapeutic problem specifically in patients with chronic pain, and is insufficiently treatable with available medication in many cases. Our research addresses cell communication in the nociceptive system, and the messenger and receptors involved, in order to identify new targets for pain therapy. We focus on pain-relevant processes in the peripheral nervous system and the spinal cord.” - Schmidtko Lab

“Research in our lab focuses on the circuit mechanisms underlying sensory computation. We use the mouse retina as a model system because it allows us to stimulate the circuit precisely with its natural input, patterns of light, and record its natural output, the spike trains of retinal ganglion cells. We harness the power of genetic manipulations and detailed information about cell types to uncover new circuits and discover their role in visual processing. Our methods include electrophysiology, computational modeling, and circuit tracing using a variety of imaging techniques.” - Schwartz Lab

“Our laboratory is focused on neurobiological engineering of next-generation molecular sensors and actuators for functional imaging and remote spatiotemporal control of cellular processes, ideally with whole‑organ(ism) coverage. We apply these molecular devices for dynamic analyses of organoids and neurobehavioral imaging of preclinical model organisms to dissect cellular network function and aid future imaging-controlled tissue engineering as well as regenerative and cell therapies.” - Westmeyer Lab

"We study signal transduction in transgenic cell and mouse models by an approach that we call "in vivo biochemistry". To this end, we use state-of-the-art transgenic mouse technology and try to "watch" biochemical processes in real time in living cells, tissues and mice. Specifically, we are interested in the role of the signalling molecule cGMP in health and disease, with a current focus on cell growth and plasticity in the mammalian cardiovascular and nervous system. The projects involve analyses at the whole organism, cellular and molecular level." - Feil Lab