Tiedt-Lab | Molecular Biomarkers – From Omics to Mechanisms
We aim to identify circulating signatures that inform on the local and systemic effects of stroke and to explore the underlying molecular and pathophysiological mechanisms. Events in most organs including the local and systemic events (e.g. stress) related to acute stroke are captured by the circulating proteome and metabolome. In a bedside-to-bench-approach we apply profiling technologies on human samples to identify differentially regulated molecules and study their functional role in vitro and in vivo using experimental stroke models, transgenic animal models, different imaging modalities, and a broad range of biomolecular tools.
Our work is motivated by the heterogeneity of ischemic stroke, which poses a challenge for assigning patients to optimal treatment strategies and is a major reason for the large number of failed clinical trials. Current diagnostic algorithms are insufficient to capture both the mechanisms leading to and following stroke. The number of circulating proteins (3.500) and metabolites (25.000) exceeds the number of proteins and metabolites currently assessed in clinical practice (≈ 20) by several orders of magnitude thus illustrating the potential of profiling studies to inform beyond established diagnostic algorithms. Our ultimate goal is to implement meaningful circulating biomarkers in clinical stroke care.
To achieve this, we have recruited more than 2,000 patients with acute stroke or stroke-like diseases into our CIRCULAting biomarkers after Stroke (CIRCULAS) study, which focuses on early and serial biosampling in the acute phase of stroke. In a precision medicine approach combining deep clinical phenotyping with profiling technologies such as RNA sequencing, proteomics, and metabolomics as well as ultrasensitive single-molecule and point-of-care technologies we have identified novel markers for stroke on different molecular levels.
Contact: Steffen Tiedt, MD PhD
Asare Y, Campbell-James TA, Bokov Y, Yu LL, Prestel M, El Bounkari O, Roth S, Megens RT, Straub T, Thomas K, Yan G, Schneider M, Ziesch N, Tiedt S, Silvestre-Roig C, Braster Q, Huang Y, Schneider M, Malik R, Haffner C, Liesz A, Soehnlein O, Bernhagen J, Dichgans M. Histone Deacetylase 9 Activates IKK to Regulate Atherosclerotic Plaque Vulnerability. Circ Res. 2020 Jun 17. Online ahead of print.
Rotkopf LT*, Tiedt S*, Puhr-Westerheide D, Herzberg M, Reidler P, Kellert L, Feil K, Thierfelder KM, Dorn F, Liebig T, Wollenweber FA, Kunz WG. Ischemic Core Volume Combined with the Relative Perfusion Ratio for Stroke Outcome Prediction after Endovascular Thrombectomy. J Neuroimaging. 2020 Feb 10. *Equally contributed.
Fabritius MP, Reidler P, Froelich MF, Rotkopf LT, Liebig T, Kellert L, Feil K, Tiedt S, Kazmierczak PM, Thierfelder KM, Puhr-Westerheide D, Kunz WG. Incremental Value of Computed Tomography Perfusion for Final Infarct Prediction in Acute Ischemic Cerebellar Stroke. J Am Heart Assoc. 2019 Nov 5;8(21):e013069
Chung J, Marini S, Pera J, Norrving B, Jimenez-Conde J, Roquer J, Fernandez-Cadenas I, Tirschwell DL, Selim M, Brown DL, Silliman SL, Worrall BB, Meschia JF, Demel S, Greenberg SM, Slowik A, Lindgren A, Schmidt R, Traylor M, Sargurupremraj M, Tiedt S, Malik R, Debette S, Dichgans M, Langefeld CD, Woo D, Rosand J, Anderson CD. Genome-wide association study of cerebral small vessel disease reveals established and novel loci. Brain. 2019 Oct 1;142(10):3176-3189.
Puhr-Westerheide D, Tiedt S, Rotkopf LT, Herzberg M, Reidler P, Fabritius MP, Kazmierczak PM, Kellert L, Feil K, Thierfelder KM, Dorn F, Liebig T, Wollenweber FA, Kunz WG. Clinical and Imaging Parameters Associated With Hyperacute Infarction Growth in Large Vessel Occlusion Stroke. Stroke. 2019 Oct;50(10):2799-2804.
Wollenweber FA, Tiedt S, Alegiani A, Alber B, Bangard C, Berrouschot J, Bode FJ, Boeckh-Behrens T, Bohner G, Bormann A, Braun M, Dorn F, Eckert B, Flottmann F, Hamann GF, Henn KH, Herzberg M, Kastrup A, Kellert L, Kraemer C, Krause L, Lehm M, Liman J, Lowens S, Mpotsaris A, Papanagiotou P, Petersen M, Petzold GC, Pfeilschifter W, Psychogios MN, Reich A, von Rennenberg R, Röther J, Schäfer JH, Siebert E, Siedow A, Solymosi L, Thonke S, Wagner M, Wunderlich S, Zweynert S, Nolte CH, Gerloff C, Thomalla G, Dichgans M, Fiehler J. Functional Outcome Following Stroke Thrombectomy in Clinical Practice. Stroke. 2019 Sep;50(9):2500-2506.
Tiedt S*, Duering M*, Barro C, Kaya AG, Boeck J, Bode FJ, Klein M, Dorn F, Gesierich B, Kellert L, Ertl-Wagner B, Goertler MW, Petzold GC, Kuhle J, Wollenweber FA, Peters N, Dichgans M. Serum Neurofilament Light: A Biomarker of Neuroaxonal Injury after Ischemic Stroke. Neurology. 2018 Oct 2;91(14):e1338-e1347. *Equally contributed.
Roth S, Singh V, Tiedt S, Schindler L, Huber G, Geerlof A, Antoine DJ, Anfray A, Orset C, Gauberti M, Fournier A, Holdt LM, Harris HE, Engelhardt B, Bianchi ME, Vivien D, Haffner C, Bernhagen J, Dichgans M, Liesz A. Brain-released alarmins and stress response synergize in accelerating atherosclerosis progression after stroke. Sci Transl Med. 2018 Mar 14;10(432).
Tiedt S, Prestel M, Malik R, Schieferdecker N, Duering M, Kautzky V, Stoycheva I, Böck J, Northoff BH, Klein M, Dorn F, Krohn K, Teupser D, Liesz A, Plesnila N, Holdt LM, Dichgans M. RNA-Seq Identifies Circulating miR-125a-5p, miR-125b-5p, and miR-143-3p as Potential Biomarkers for Acute Ischemic Stroke. Circ Res. 2017 Sep 29;121(8):970-980.
Vanessa Granja Burbano, PhD student
Originally from Ecuador, I obtained my BSc degree in Biology at Cayetano Heredia University in Peru and worked as a research assistant at the Department of Neurobiology, Genetics and Biochemistry. In 2016, I moved to Germany to pursue a MSc degree in Experimental and Clinical Neuroscience at the University of Regensburg. My master thesis was focused on the analysis of mitochondrial dysfunction in induced neurons obtained from patients with Major Depressive Disorder. Obtaining a DAAD scholarship from the iPUR program, I was able to work at the University of Regensburg as guest researcher with Dr. Oliver Bosch. My main research interests include neurodegenerative, cardiovascular, and age-related diseases. I have joined the Tiedt Lab at the ISD in 2020 as a PhD student at the Graduate School of Systemic Neurosciences (GSN). Primary focus of my work is to investigate the impact of the circadian rhythm on stroke. Outside the lab, I enjoy dancing salsa, reading tons of books and hiking.
Evan Hunter Stanton, PhD student
I am originally from the United States, where I began my research career as an undergraduate at the University of Wisconsin at Madison in the animal behavior-oriented lab of Dr. Catherine Marler. From there, I conducted a neurodegeneration-focused internship with Dr. Sally Temple, where I contributed to organoid experiments at the Neural Stem Cell Institute in Rensselaer, New York. My academic path then took me to Germany, where I obtained my master’s degree at the University of Regensburg under Dr. Mark Greenlee, as well as under the collaborative mentorship of Dr. Maiken Nedergaard at the University of Copenhagen. Through my studies, I have developed a passion for systemic neuroscience and acute insults of the central nervous system. I joined the Tiedt Lab to continue this pursuit, and to explore the role of circulating biomarkers in the setting of ischemic stroke. When I am active outside the lab, I enjoy hiking and playing squash. However, when relaxing at home, I enjoy reading on mythology in early civilizations, as well as writing poetry.
Teresa Wölfer, MD student
Originally coming from Berlin I moved to Munich to start my medical studies in 2016. Very soon I developed a strong interest in Neurology which led me to pursue an experimental MD thesis at the Tiedt Lab at ISD to really get a deeper understanding of stroke research. While focusing my work on circulating biomarkers of ischemic stroke, I strive to gain insight into the methods and workflow of neuroscience research. Also having a keen interest in History and Philosophy I began my bachelor studies at the LMU in 2019. Outside the lab I like to visit the Alps (a new passion of mine), enjoy making some pottery or ride my bike through Munich’s parks.
Melanie Kaufmann, MD student
I am originally from a rural region in the east of Bavaria and I came to Munich a few years before I started my medical studies in 2015 to do an apprenticeship in the medical field. Therefore, in addition to my studies, I am already working in the clinical area in an intensive care unit in nursing and so I can already gain initial experience in patient care.The complex mechanisms of the human body have always fascinated and inspired me. However also the topicality and relevance of neurovascular diseases have motivated me coming to the ISD in August 2020 to deal more intensively with stroke in particular. When I'm not working or studying, I spend a lot of time in my home community doing various voluntary activities or I‘m hiking, cycling or climbing in the mountains.
Michael Karg, MD student
Born and raised in Munich I am, as we say, a “Münchner Kindl”. After I passed my A-levels in 2016, I started my medical studies at the LMU in Munich in the following semester (16/17). Since 2018 I am glad to call Dr. Konstantinos Dimitriadis (senior physician in neurology at LMU) my mentor. I am very thankful for the mentorship, which allowed me to gain a deeper understanding in the field of neurology and the scientific research which is done at the ISD. In October 2018, I started my own research under the leadership of Dr. Steffen Tiedt. My subject is the the prevalence of systemic complications and prediction of thrombectomy success, interventional complications, and functional outcome after thrombectomy. Besides from my passion for medicine and its research, I am a big fan of intercultural exchanges in Europe and the whole world, which is why I speak four languages and of course I support the world’s best soccer club FC Bayern München.
Charlotte Forster, MD student
My scientific goal is to identify meaningful circulating signatures that inform on pathophysiological mechanisms after stroke and can be utilized as diagnostic instruments. Implementing these in clinical routine I envision stroke care to be more comprehensive and precise.
I studied medicine at LMU and Harvard. Intrigued by courses on neurophysiology, I conducted my MD thesis with Magdalena Götz exploring the role of STAT-signaling on the neurogenic potential of reactive astrocytes. In 2013, I joined the group of Martin Dichgans at the ISD as a clinician-scientist conducting a joint program: a PhD in Neuroscience at the Graduate School of Systemic Neuroscience and residency in Clinical Neurology. During my PhD I initiated the CIRCULAting biomarkers after Stroke (CIRCULAS) study, which by now is the largest study world-wide with early and serial blood sampling in acute stroke patients (N>2,000). Utilizing this resource, we were the first to employ RNA sequencing for the identification of circulating miRNAs associated with stroke and to apply single-molecule array (SimoaTM) technology during the course of stroke (publications in Circulation Research and Neurology).
Based on this work, my lab now utilizes profiling, ultrasensitive single-molecule, and point-of-care technologies to identify meaningful signatures to improve stroke care and explores underlying molecular and pathophysiological mechanisms in experimental settings.
2014 – 2018
PhD in Neuroscience (Title: “The role of blood-based biomarkers in ischemic stroke”) at the Graduate School of Systemic Neurosciences and Institute for Stroke and Dementia Research, LMU (Prof. Dr. M. Dichgans)
2009 – 2015
MD thesis (Title: „Regeneration of neurons after brain injury: role of the STAT-signaling pathway in the inhibition of neurogenesis of reactive astrocytes“) at the Institute of Physiology, LMU (Prof. Dr. M. Götz; Summa cum laude)
Residency in Neurology at the Institute for Stroke and Dementia Research (Prof. Dr. M. Dichgans) and Department of Neurology, LMU (Prof. Dr. M. Dieterich)
2006 – 2013
Medical studies at the LMU Munich & Harvard Medical School (MA, USA)
Scholarships & Awards:
Mentor of the Year (Medical faculty, LMU)
Clinician-Scientist-Program PRIME (DFG, LMU)
Young Investigator Award (European Stroke Organization)
2018 – 2019
MOMENTE-Program for outstanding postdoctoral researchers (LMU)
2016 – 2018
Clinician-Scientist-Program (Cluster of Excellence SyNergy)
Individual research scholarship (Josef-Hackl-Foundation)
2011 – 2012
Program for excellent medical students (MeCuM-StEP, LMU)
We gratefully acknowledge funding by the following funding agencies:
Excellence program for research and funding (FöFoLe, LMU)