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                                                  3. Erturk Lab

                                                  Ali Erturk – 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


                                                  Dr. Ali Ertürk, PI

                                                  Mayar Ali, Ph.D. Candidate

                                                  Rami Al-Maskari, Ph.D. Candidate

                                                  Dr. Harsharan S. Bhatia, Postdoc

                                                  Karen Biniossek, Team Assistant

                                                  Marin Bralo, Technical Assistant

                                                  Dr. Süheda Erener, Science Manager

                                                  Basavdatta Pulok Gupta, Master Student

                                                  Dr. Farida Hellal, Postdoc

                                                  Luciano Jan Hoeher, Master Student

                                                  Izabela Horvath, Ph.D. Candidate

                                                  Louiza Ignatiou, Master Student

                                                  Dr. Doris Kaltenecker, Postdoc

                                                  Karoline Kadletz, Ph.D. Candidate

                                                  Ilgin Kolabas, Ph.D. Candidate

                                                  Louis Kümmerle, Ph.D. Candidate

                                                  Dr. Jie Luo, Postdoc

                                                  Hongcheng Mai, Ph.D. Candidate

                                                  Muge Molbay Ph.D. Candidate

                                                  Furkan Ozturk, Ph.D. Candidate

                                                  Johannes Paetzold, Ph.D. Candidate

                                                  Dr. Chenchen Pan, Postdoc

                                                  Zhouyi Rong, PhD Candidate

                                                  Mihail Todorov, Ph.D. Candidate

                                                  Ana Toman Fabjan, Team Assistant

                                                  Dr. Alison Wright, Postdoc



                                                  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, 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.

                                                  Personal data, Born: Sep. 1980

                                                  Website: www.erturk-lab.com email: erturk@deeppiction.com

                                                  Twitter: erturklab (67.8K followers) LinkedIn: LinkedIn

                                                  Current positions

                                                  09/2022-current: CEO, founder, 1X1 Biotech

                                                  02/2022-current: CEO, founder, Deep Piction

                                                  07/2022–current: W3 (Full) Professor, LMU Munich, Germany

                                                  07/2019–current: Director, Institute for Tissue Engineering & Regenerative Medicine, Helmholtz Munich

                                                  Research interests

                                                  • Aim: Developing and combining unbiased & scalable technologies for better diagnostics and therapeutics

                                                  • Focus: Tissue clearing, Spatial-omics, Imaging, Organoids, Neurodegeneration, Cancer, Nanotechnology, Delivery

                                                  Education and training (details in appendix 1)

                                                  2009–2014: Postdoctoral fellow at Genentech Inc., South San Francisco

                                                  2003–2009: Doctoral thesis at Max–Planck–Institute of Neurobiology, Munich

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

                                                  Honors & Awards

                                                  • 2021 Nomis Foundation Human Heart Atlas Award

                                                  • 2021 Scientific vision highlighted in Brandeins article

                                                  • 2020 Vision on extending human life highlighted by Focus Magazine

                                                  • 2020 Rolf Becker-Preis 2020

                                                  • 2020 Scientific and personal career profiled in Nature Methods

                                                  • 2020 ERC Consolidator Grant, European Research Council

                                                  • 2020 Cure Alzheimer’s Foundation researcher

                                                  • 2020 Media coverage by Reuters, NZZ, Telegram, Daily Mail, RTL, Focus, Sat1 and Süddeutsche Zeitung, Galileo

                                                  • 2019 Interviewed as one of the 7 scientists in “Brain gain in Germany…” by Focus Magazine

                                                  • 2017 NIH R01 grant award

                                                  • 2017 Adjunct Professor at the Rochester University (New York)

                                                  • 2017 Fritz Thyssen Stiftung Investigator Award

                                                  • 2016 Interviewed by New York Times and Wall Street Journal

                                                  • 2014 Sofja Kovalevskaja Award from Humboldt Foundation (declined)

                                                  • 2014 Associate Investigator of DFG Excellent cluster of Munich SyNergy and SyNergy II

                                                  Publications as PI/corresponding author

                                                  • Bhatia...Ertürk A. Spatial proteomics in optically cleared pre-clinical & clinical specimens, Cell (in press) (cover)

                                                  • Cai M…Ertürk A. Cellular level whole mouse imaging with vDISCO…Nat. Protocols (in press)

                                                  • Kolobas I…Ertürk A. Multi-omics and 3D-imaging reveal bone heterogeneity…(bioRxiv)

                                                  • Mai…Ertürk A. Scalable SHANEL Tissue Labelling and Clearing…Nat. Protocols (Oct 2022)

                                                  • Todorov M…Ertürk A. Machine learning analysis of whole mouse brain vasculature. Nature Methods, Apr. 2020

                                                  • Zhao S…Ertürk A. Cellular and Molecular Probing of Intact Human Organs. Cell, Feb. 2020 (video)

                                                  • Pan C…Ertürk A. Deep learning reveals cancer metastasis & therapeutic antibody… Cell, Dec. 2019 (cover) (video)

                                                  • Cai R…Ertürk A. Panoptic imaging of transparent mice reveals… Nature Neuroscience, Feb. 2019 (cover)

                                                  • Pan C…Ertürk A. Shrinkage-mediated imaging of entire organs by uDISCO. Nature Methods, Oct. 2016 (cover)  

                                                  Average impact factor of all articles as PI > 44

                                                  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


                                                  2022

                                                  Bhatia HS, Brunner AD, Öztürk F, Kapoor S, Rong Z, Mai H, Thielert M, Ali M, Al-Maskari R, Paetzold JC, Kofler F, Todorov MI, Molbay M, Kolabas ZI, Negwer M, Hoeher L, Steinke H, Dima A, Gupta B, Kaltenecker D, Caliskan ÖS, Brandt D, Krahmer N, Müller S, Lichtenthaler SF, Hellal F, Bechmann I, Menze B, Theis F, Mann M, Ertürk A. Spatial proteomics in three-dimensional intact specimens. Cell. 2022 Dec 22;185(26):5040-5058.e19. doi: 10.1016/j.cell.2022.11.021. 

                                                  Mai H, Rong Z, Zhao S, Cai R, Steinke H, Bechmann I, Ertürk A. Scalable tissue labeling and clearing of intact human organs. Nat Protoc. 2022 Jul 20. doi: 10.1038/s41596-022-00712-8. Epub ahead of print. 

                                                  2021

                                                  Molbay M, Kolabas ZI, Todorov MI, Ohn TL, Ertürk A. A guidebook for DISCO tissue clearing. Mol Syst Biol. 2021 Mar;17(3):e9807. doi: 10.15252/msb.20209807. 

                                                  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. 

                                                  Wang X, Lou N, Eberhardt A, Yang Y, Kusk P, Xu Q, Förstera B, Peng S, Shi M, Ladrón-de-Guevara A, Delle C, Sigurdsson B, Xavier ALR, Ertürk A, Libby RT, Chen L, Thrane AS, Nedergaard M. An ocular glymphatic clearance system removes β-amyloid from the rodent eye. Sci Transl Med. 2020 Mar 25;12(536):eaaw3210. 

                                                  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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                                                  Institute for Stroke and Dementia Research (ISD)
                                                  University Hospital, LMU Munich

                                                  Director: Prof. Dr. med. Martin Dichgans

                                                  Feodor-Lynen-Straße 17
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                                                  www.isd-research.de
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