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                                      1. ISD Research
                                      2. Research Groups
                                      3. ErturkLab

                                      ErturkLab – Acute Brain Injury

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                                      A fundamental challenge in modern science is to understand how the brain functions in health and what goes wrong in the disease state. We develop and implement 3D imaging technologies to be able to generate the highest resolution views of intact rodent organs and bodies. We developed DISCO line tissues transparency technologies, which have been a great utility for scientists from diverse bio-medical research fields. Overall, this approach provides a holistic view of inter connected biological systems to perceive biological mechanisms in an unbiased way.

                                      Our laboratory is interested in understanding key mechanisms leading to neurodegeneration after acute brain injuries, mainly stroke and dementia. To this quest, we take a multidisciplinary approach by using advanced neuroscience imaging, genetic engineering, nanotechnology and artificial intelligence.

                                      While many diseases affect the entire body, research is usually conducted on the tissue of interest ignoring 99% rest of the organism. My lab believes that we need to see organism as a whole to correctly assess all biological systems affecting each other. Therefore, we use a holistic approach in research to overcome potential bias and discover essential cellular and molecular mechanisms in toto. Towards this goal, we have developed cutting-edge tissue transparency methods allowing 3D histology on intact organisms. We can now collect information on whole organism at the sub-cellular levels without sectioning. Obtained imaged data for example can for the first-time present the complete neuronal connectivity at single neuronal level, and determine what goes wrong in a neurological disease. We use machine-learning based image analysis methods to analyze these large imaging data. Finally, we are focusing on developing nanotechnology (nano-robots) to treat neurological diseases in a novel and potent way.

                                      Contact: Dr. Ali Erturk
                                      E-Mail: ali.ertuerk@med.uni-muenchen.de


                                      Ertürk, Ali, Dr., PI

                                      Rami Al-Maskari, Ph.D. Candidate

                                      Dr. Harsharan S. Bhatia, Postdoc

                                      Karen Biniossek, Team Assistant

                                      Marin Bralo, Technical Assistant

                                      Dr. Benjamin Förstera, Postdoc

                                      Dr. Farida Hellal, Postdoc

                                      Izabela Horvath, Ph.D. Candidate

                                      Dr. Doris Kaltenecker, Postdoc

                                      Ilgin Kolabas, Ph.D. Candidate

                                      Louis Kümmerle, Ph.D. Candidate

                                      Hongcheng Mai, Ph.D. Candidate

                                      Muge Molbay Ph.D. Candidate

                                      Dr. Tzu-Lun Ohn, Postdoc

                                      Furkan Ozturk, Ph.D. Candidate

                                      Johannes Paetzold, Ph.D. Candidate

                                      Dr. Chenchen Pan, Postdoc

                                      Zhouyi Rong, PhD Candidate

                                      Oliver Schoppe, Group Leader: Artificial Intelligence

                                      Dr. Karen Stanic, Postdoc

                                      Mihail Todorov, Ph.D. Candidate

                                      Ana Toman Fabjan, Team Assistant

                                      Dr. Alison Wright, Postdoc

                                      Shan Zhao, Ph.D. Candidate



                                      ALMUNI:

                                      Postdocs:

                                      Lamia’a Bahnassawy

                                      Francesca Paola Quacquarelli

                                      Rupinder Kaur

                                      Ph.D. Students:

                                      Marika Ruiyao Cai

                                      Master’s Students:

                                      Leander Mrowka

                                      Christoph Dehner

                                      Madita Reimer

                                      Ali Erturk

                                      Ali Erturk, Principal investigator

                                      I studied genetic engineering and molecular biology. My research has mainly focused on mechanisms of neurodegenerative diseases and developing new imaging tools to decipher details of complex biological systems in the whole organism.

                                      Science has advanced enormously in the recent decades, however, we still lack effective treatments for devastating diseases such as stroke and dementia, partly due to incremental progress, where the majority of scientific effort focuses on the next “predicted” mechanisms. I believe a multi-disciplinary approach combining the expertise of diverse fields such as advance imaging, genetic engineering, nanotechnology and artificial intelligence will be a key to obtain “unbiased” readouts on biological systems and come up with breakthrough solutions to cure all diseases including the aging in the next a few decades.

                                      We are an organism of interconnected systems from head-to-toe, via for example wiring of neurons and vessels. Thus, it is natural that most of the biological events will impact the whole-body, not only a small region. However, there is hardly any effort to study biological systems as a whole in research, also due to lack of methods that can provide readouts in the whole body at the cellular and molecular level. Towards this goal, we develop and use whole mouse transparency technologies (e.g., Ertürk et al., 2012 Nature Medicine, Pan et al., 2016 Nature Methods), enabling us to have a holistic view on cellular and molecular mechanisms in health and disease. For example, we study the effects of acute brain injuries not only in the brain but also throughout the whole nervous system and the body. We are also focusing on artificial intelligence to analyze the large data sets and nanorobots to discover new ways of drug delivery into the brain.

                                      Current academic positions

                                      07/2014–now: Independent group leader, Institute for Stroke and Dementia (ISD), Ludwig Maximilians-University of Munich (LMU), Germany

                                      01/2017–now: Adjunct Assistant Professor, Rochester University, New York, USA

                                      Education and training

                                      2009–2014: Postdoctoral fellow at Genentech Inc., South San Francisco, (Supervisor: Morgan Sheng, VP of Genentech Neuroscience).

                                      2003–2009: Doctoral thesis at Max–Planck–Institute of Neurobiology, (Supervisor: Frank Bradke, DZNE Bonn)

                                      2002: Intern, Harvard University. School of Medicine, Timothy Vartanian lab

                                      2001: Intern, Yale University, School of Medicine, Hal Blumenfeld lab

                                      1998–2003: Bachelor of Science, Bilkent University, Molecular Biology and Genetics, Ankara

                                      Funding

                                      2018-2023: R01, NIH, USA

                                      2014-2019: Solorz-Żak’s Foundation (Institute for Stroke and Dementia)

                                      2017-2019: Fritz Thyssen Stiftung, Germany

                                      2016-2019: DFG Research Grant

                                      2015-2019: Excellent cluster of Munich SyNergy

                                      2016-2018: Helmholtz Alliance ICEMED

                                      2015-2018: ERA-Net Neuron, European Research Council

                                      2015-2017: LMU Excellent seeding funds and FöFoLe research grants

                                      Honors & Awards

                                      2017: Fritz Thyssen Stiftung investigator award

                                      2016: Interviewed by New York Times and Wall Street Journal for our novel technologies

                                      2014: Sofja Kovalevskaja Award from Humboldt Foundation (offered)

                                      2009–2014: Genentech postdoctoral program

                                      2004–2007: Marie Curie PhD fellowship from European Resreach Concil

                                      1998–2003: Full education scholarship awarded by Bilkent University

                                      1998–2003: Scholarship awarded by The Scientific and Technological Research Council of Turkey

                                      Brain Vasculature

                                      3sat br

                                      A visit from Nano – 3sat Mediathek.

                                      May 2020

                                      Today at the lab we were very lucky to have a team from the Bayerisches Fernsehen come to our lab space at the Institute for Stroke and Dementia Research (ISD) and take a look at some of the cleared tissues we’ve produced.

                                      Hear all about it on Nano, this Saturday, aired on 3sat or streamed online at the 3sat website.


                                      VesSAP

                                      VesSAP is out

                                      March 2020

                                      Machine learning analysis of whole mouse brain vasculature. Now published: Todorov et al., https://www-nature-com.emedien.ub.uni-muenchen.de/articles/s41592-020-0792-1


                                      Brain Vasculature

                                      New Paper

                                      February 2020

                                      Our work on AI-based analysis of the entire brain vasculature is now in press. This is the 5th publication of erturklab in its 5 years of existence. Congratulations to all team members and the collaborators, including Bjoern Menze and his lab. (March 2020) .

                                      Todorov M, Paetzold J, Schoppe O,…Ertürk A. Automated analysis of whole brain vasculature using machine learning. bioRxiv version


                                      Transparent Organs

                                      Our 4th Paper in Cell

                                      February 2020

                                      Our 4th publication also appears in Cell. We developed the first to technology to make intact human organs transparent for cellular & molecular mapping using novel tissue chemistry, light-sheet microscopy, and machine learning. The image below shows the highest resolution of the intact human kidney ever obtained. https://www.cell.com/cell/fulltext/S0092-8674(20)30111-2


                                      cure alzheimer's

                                      Cure Alzheimer’s Fund

                                      February 2020

                                      We received a grant from Cure Alzheimer’s Fund in a consortium led by Jony Kipnis. We will investigate the role of skull-meninges connections in relation to the lymphatic/glymphatic system and blood-brain barrier.


                                      Cell Cover

                                      Paper in Cell

                                      December 2019

                                      Our lab publishes its 3rd article at Cell as the cover story. We developed an AI (deep learning) based technology to analyze cancer metastasis & therapeutic antibody targeting at single-cell level in the whole mouse.


                                      Publications by Ali Ertürk


                                      2020

                                      Todorov MI, Paetzold JC, Schoppe O, Tetteh G, Shit S, Efremov V, Todorov-Völgyi K, Düring M, Dichgans M, Piraud M, Menze B, Ertürk A. Machine learning analysis of whole mouse brain vasculature. Nat Methods. 2020 Apr;17(4):442-449. 

                                      Zhao S, Todorov MI, Cai R, et al. Cellular and Molecular Probing of Intact Human Organs. Cell. 2020;180(4):796–812.e19. 

                                      Ueda HR, Ertürk A, Chung K, Gradinaru V, Chédotal A, Tomancak P, Keller PJ. Tissue clearing and its applications in neuroscience. Nat Rev Neurosci. 2020 Feb;21(2):61-79.


                                      2019

                                      Pan C, Schoppe O, Parra-Damas A, Cai R, Todorov MI, Gondi G, von Neubeck B, Böğürcü-Seidel N, Seidel S, Sleiman K, Veltkamp C, Förstera B, Mai H, Rong Z, Trompak O, Ghasemigharagoz A, Reimer MA, Cuesta AM, Coronel J, Jeremias I, Saur D, Acker-Palmer A, Acker T, Garvalov BK, Menze B, Zeidler R, Ertürk A. Deep Learning Reveals Cancer Metastasis and Therapeutic Antibody Targeting in the Entire Body. Cell. 2019 Dec 12;179(7):1661-1676.e19. 

                                      Cai R, Pan C, Ghasemigharagoz A, Todorov MI, Förstera B, Zhao S, Bhatia HS, Parra-Damas A, Mrowka L, Theodorou D, Rempfler M, Xavier ALR, Kress BT, Benakis C, Steinke H, Liebscher S, Bechmann I, Liesz A, Menze B, Kerschensteiner M, Nedergaard M, Ertürk A. Panoptic imaging of transparent mice reveals whole-body neuronal projections and skull-meninges connections. Nat Neurosci. 2019 Feb;22(2):317-327. 

                                      Parhizkar S, Arzberger T, Brendel M, Kleinberger G, Deussing M, Focke C, Nuscher B, Xiong M, Ghasemigharagoz A, Katzmarski N, Krasemann S, Lichtenthaler SF, Müller SA, Colombo A, Monasor LS, Tahirovic S, Herms J, Willem M, Pettkus N, Butovsky O, Bartenstein P, Edbauer D, Rominger A, Ertürk A, Grathwohl SA, Neher JJ, Holtzman DM, Meyer-Luehmann M, Haass C. Loss of TREM2 function increases amyloid seeding but reduces plaque-associated ApoE. Nat Neurosci. 2019 Feb;22(2):191-204. 


                                      2018

                                      von Neubeck B, Gondi G, Riganti C, Pan C, Parra Damas A, Scherb H, Ertürk A, Zeidler R. An inhibitory antibody targeting carbonic anhydrase XII abrogates chemoresistance and significantly reduces lung metastases in an orthotopic breast cancer model in vivo. Int J Cancer. 2018 Oct 15;143(8):2065-2075. 


                                      2017

                                      Llovera G, Benakis C, Enzmann G, Cai R, Arzberger T, Ghasemigharagoz A, Mao X, Malik R, Lazarevic I, Liebscher S, Ertürk A, Meissner L, Vivien D, Haffner C, Plesnila N, Montaner J, Engelhardt B, Liesz A. The choroid plexus is a key cerebral invasion route for T cells after stroke. Acta Neuropathol. 2017 Dec;134(6):851-868.

                                      Garvalov BK, Ertürk A. Seeing whole-tumour heterogeneity. Nat Biomed Eng. 2017 Oct;1(10):772-774. 


                                      2016

                                      Pan C, Cai R, Quacquarelli FP, Ghasemigharagoz A, Lourbopoulos A, Matryba P, Plesnila N, Dichgans M, Hellal F, Ertürk A. Shrinkage-mediated imaging of entire organs and organisms using uDISCO. Nat Methods. 2016 Oct;13(10):859-67. 

                                      Ertürk A, Mentz S, Stout EE, Hedehus M, Dominguez SL, Neumaier L, Krammer F, Llovera G, Srinivasan K, Hansen DV, Liesz A, Scearce-Levie KA, Sheng M. Interfering with the Chronic Immune Response Rescues Chronic Degeneration After Traumatic Brain Injury. J Neurosci. 2016 Sep 21;36(38):9962-75.


                                      2015

                                      Lourbopoulos A, Ertürk A, Hellal F. Microglia in action: how aging and injury can change the brain's guardians. Front Cell Neurosci. 2015 Feb 23;9:54. 


                                      2014

                                      Ertürk A, Wang Y, Sheng M. Local pruning of dendrites and spines by caspase-3-dependent and proteasome-limited mechanisms. J Neurosci. 2014 Jan 29;34(5):1672-88. 

                                      Chen Y, Wang Y, Ertürk A, Kallop D, Jiang Z, Weimer RM, Kaminker J, Sheng M. Activity-induced Nr4a1 regulates spine density and distribution pattern of excitatory synapses in pyramidal neurons. Neuron. 2014 Jul 16;83(2):431-443. 

                                      Ertürk A, Lafkas D, Chalouni C. Imaging cleared intact biological systems at a cellular level by 3DISCO. J Vis Exp. 2014 Jul 7;(89).

                                      2013

                                      Sheng M, Ertürk A. Long-term depression: a cell biological view. Philos Trans R Soc Lond B Biol Sci. 2013 Dec 2;369(1633):20130138. 

                                      Ertürk A, Bradke F. High-resolution imaging of entire organs by 3-dimensional imaging of solvent cleared organs (3DISCO). Exp Neurol. 2013 Apr;242:57-64.


                                      2012

                                      Ertürk A, Becker K, Jährling N, Mauch CP, Hojer CD, Egen JG, Hellal F, Bradke F, Sheng M, Dodt HU. Three-dimensional imaging of solvent-cleared organs using 3DISCO. Nat Protoc. 2012 Nov;7(11):1983-95.


                                      2011

                                      Ertürk A, Mauch CP, Hellal F, Förstner F, Keck T, Becker K, Jährling N, Steffens H, Richter M, Hübener M, Kramer E, Kirchhoff F, Dodt HU, Bradke F. Three-dimensional imaging of the unsectioned adult spinal cord to assess axon regeneration and glial responses after injury. Nat Med. 2011 Dec 25;18(1):166-71. 


                                      2010

                                      Usher LC, Johnstone A, Ertürk A, Hu Y, Strikis D, Wanner IB, Moorman S, Lee JW, Min J, Ha HH, Duan Y, Hoffman S, Goldberg JL, Bradke F, Chang YT, Lemmon VP, Bixby JL. A chemical screen identifies novel compounds that overcome glial-mediated inhibition of neuronal regeneration. J Neurosci. 2010 Mar 31;30(13):4693-706. 


                                      2009

                                      Ylera B, Ertürk A, Hellal F, Nadrigny F, Hurtado A, Tahirovic S, Oudega M, Kirchhoff F, Bradke F. Chronically CNS-injured adult sensory neurons gain regenerative competence upon a lesion of their peripheral axon. Curr Biol. 2009 Jun 9;19(11):930-6. 

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                                      University Hospital, LMU Munich

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                                      www.isd-research.de
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