Vienna, Vienna, Austria
I am a medical neuroscientist by training and I have dedicated my career to studying the etiology and pathophysiology of neurodegeneration, cerebrovascular disease, and brain aging, as well as to developing effective therapeutic approaches for the functional recovery of the injured brain. I enjoy the reputation of an internationally visible expert in cell death signaling having characterized the signaling pathways leading to neuronal demise after stroke. A detailed molecular understanding of how different brain cells enable brain function and participate in degenerative and regenerative processes after injury as well as which life-spanning neuronal and extraneuronal changes lead to neurodegeneration at later stages in life is essential for the design of successful treatment strategies.
Cerebrovascular diseases, such as stroke, brain hemorrhage, and dementia, are the leading causes of death and disability and present an enormous socioeconomic burden worldwide. Current estimates predict that their prevalence will further increase as 25 % of the population will be over 65 years of age by 2030. Current explicative models of these diseases account for signs and symptoms that are already present in affected patients. However, we now know that these diseases are life-spanning processes that start silently at least 20 to 30 years before symptoms are perceived. It is therefore difficult to identify real cause from mere consequences. Our research group aims to identify the underlying etiology of cerebrovascular disease and brain aging in addition to studying its pathophysiology in order to identify novel targets and to develop innovative therapies for prevention, cytoprotection, regeneration, and recovery of motor and cognitive function that are limited in patients suffering from these devastating diseases. Our current projects are: 1. Unraveling the mechanisms of axonal degeneration after brain hemorrhage 2. Investigating the role of brain endothelial cell death in hemorrhagic and ischemic brain injury 3. Studying hypertension as a model to understand the lifespan vascular changes leading to cerebrovascular diseases 4. Identifying bioactive compounds for healthy brain aging
Our research group aims to identify the underlying etiology of cerebrovascular disease in addition to studying its pathophysiology in order to develop novel therapeutic options. Our current projects are: 1. Unraveling the mechanisms of axonal degeneration after brain hemorrhage 2. Investigating the role of brain endothelial cell death in hemorrhagic and ischemic brain injury 3. Studying hypertension as a model to understand the lifespan vascular changes leading to cerebrovascular diseases Lecturer activities: Seminar series on “glucocorticoids and vitamins” as well as “thyroid hormons and calcium homeostasis” (Pharmacology and Toxicology, 10x 4 academic hours) for medical students, Seminar series on “Blood pharmacology” as well as “Lung pharmacology” (Pharmacology and Toxicology, 10x 4 academic hours) for medical students, poster judge for poster of medical students (Clinical Environmental Medicine, 3x 4 academic hours), instructor for problem-based learning in Clinical Environmental Medicine for medical students, lecture for Master students of Molecular Life Science on “Cerebrovascular Pharmacology” (Drug Research – Module A “Pharmacology and Toxicology”, 1x 2 academic hours), lecture for undergraduate students of Environmental Engineering on “Cancerogens” (Toxicology, 5x 2 academic hours), lecture for undergraduate students Midwifery on “Antihypertensive treatment during pregnancy” (Module Fundamentals of Clinical Medicine and Pharmacology, 1x 2 academic hours) Obtained Teaching Certificate “Micro Certificate HD I” (and currently working on Certificate HD II from the German Association for Educational and Academic Staff Development in Higher Education (dghd)). Supervision of one PhD student, one MD student, one MSc student, and one BSc student
The research group CNS Regeneration develops novel therapeutic options for stroke, brain hemorrhage, and vascular dementia. Using cutting-edge scientific approaches and technologies, we aim to better understand the nervous system. This enables us to develop innovative therapies for neuroprotection, regeneration, and recovery of motor and cognitive function that are limited in patients suffering from these devastating diseases. One area of research is to improve existing and develop novel test systems and models of cerebrovascular diseases. Importantly, we focus on improving predictability of our cell culture and animal models for the clinical situation and to better represent the heterogeneity in the patient population. Another focus is the development of test systems and models of damage to nerve fibers and their regeneration. More and more studies show that in addition to death of neurons, damage to nerve fibers is a prominent feature of numerous neurologic diseases. Degeneration of axons can occur far away from the site of injury and limits recovery of motor and cognitive function in patients. To date, a test system to investigate axonal degeneration and regeneration systematically, with high content, and increased throughput is lacking. Our group currently develops a high-content screening to enable assessment of drugs that prevent axonal degeneration and promote regeneration of damaged fibers. Funding 2018-2020: Fraunhofer Society MEF EnTireAxon 2018-2019: BMBF MERCEDES 2018-2019: BMBF NEPTUN Supervision of one PhD student, five Master students (four lab rotations, one Master thesis completed), two Bachelor students (two Bachelor theses completed), 4 student workers Course manager of weekly Journal Club at the institute Submitted one patent application
Supervisor: Rajiv R. Ratan During my postdoctoral training, I specialized in pharmacological and molecular strategies to ma-nipulate cell death signaling pathways to pinpoint affector from effector events. I investigated different cell death stimuli in neurons and cancer cells and found that they actively respond to the stimulus by inducing a transcriptional response in an attempt to reestablish cellular homeostasis (Zille et al., 2017; Zille et al., eNeu-ro, 2019). If this fails, the cells actively induce different cell death subroutines. I systematically characterized the cell death signaling after intracerebral hemorrhage and found that it shares features of ferroptotic and necroptotic cell death, but not caspase-dependent apoptosis or autophagy. To our knowledge, hemin and hemoglobin are the first death stimuli described to involve a mixture of necroptotic and ferroptotic features. We proposed that ferroptosis or necroptotic signaling induced by lysed blood is sufficient to reach a threshold of death that leads to neuronal necrosis and that inhibition of either one of these pathways can bring cells below that threshold to survival (Zille et al., 2017). These findings will have a strong impact on future research in stroke, as they demonstrate that molecular mechanisms of ischemic and hemorrhagic stroke are likely different and may require distinct treatment strategies, i.e. aberrant oxidant damage (parthanatos, murder) vs. aberrant oxidant signaling (necroptosis and ferroptosis, suicide), respectively. Achievements: 1) received research fellowship of the German Research Foundation 2) published 7 peer-reviewed manuscripts 3) contributed 2 talks and 3 posters to scientific conferences 4) became expert member of the HEADS (HEmorrhagic stroke acAdemia inDuStry roundtable) 5) was postdoctoral representative 6) supervised one High School Student who was named top 300 scholar in the Regeneron Science Talent Search 7) was course manager of the Postdoctoral Journal Club
Supervisors: Prof. Ulrich Dirnagl / PD Dr. rer. nat. Andreas Wunder Deptartment of Experimental Neurology During my PhD, I investigated the role of Annexin A5 as a noninvasive marker for cell death after stroke using multiple in vivo imaging modalities. Annexin A5 has been widely used for imaging cell death under various disease conditions. It had been described earlier for the use in stroke both in animal models and in humans. Our results showed that a near-infrared fluorescently labeled Annexin A5 was suitable for the imaging of cell death after focal cerebral ischemia in vivo in the mouse (Bahmani et al., 2011), while a dual-labeled AnxA5 was not suitable for single-photon emission computed tomography (Zille et al., 2014). This was an important finding, which led to the development of a novel AnxA5 which allows long circulation of the protein (Haeckel et al., 2014). In addition, I also was a course instructor, managed the Neuroscience Journal and Methods Club, was a student representative in our graduate program, and supervised a Master student. During my PhD, I was also the Chief Editor of the Charité NeuroSience (CNS) Newsletter (Quarterly). I coordinated an editorial team of 5 and 8 writers for a total of 15 issues, composed the newsletters, distributed the topics, engaged with sponsors, and wrote and proofread articles. Achievements: 1) published 10 peer-reviewed manuscripts 2) received a PhD scholarship 3) received the Robert-Koch Preis of the Charité Berlin for the best PhD thesis in 2014/15 4) received the Best Talk Award at the Berlin Brain Days 2013 5) received three travel grants to attend international scientific conferences 6) published 15 issues of the CNS Newsletter as editor-in-chief 7) contributed 3 talks and 6 posters to scientific conferences 8) supervised one Master student 9) was a student representative of our graduate program 10) held seminars and lectures 11) managed the Neuroscience Journal and Methods Club