"MITOCHONDRIA & INFLAMMATION IN NEURODEGENERATIVE DISEASES"
Overview of Our Research
The Deleidi Lab "Mitochondria & Inflammation in Neurodegenerative Diseases" is a research lab at the German Center for Neurodegenerative Disease (Tübingen). The lab was founded in 2016 in the framework of the Helmholtz Young Investigator Group program. Research in our laboratory concentrates on the molecular mechanisms of neurodegeneration, with a special emphasis on Parkinson's disease.
Our research aims at studying how discrete genetic factors contribute to the development of neurological disorders, with a particular focus on Parkinson's disease (PD). To this end, we develop models with human pluripotent stem cells and long-term cultures of organoids combined with single cell-omics to identify the role of disease related genetic variants and validate targets with diagnostic and therapeutic potential.
THE INNATE IMMUNE SYSTEM IN NEURODEGENERATIVE DISEASES
Several genetic clues link inflammation to neurodegenerative diseases. With this respect, it is interesting to note that many disease-linked genes (in AD, ALS and PD) are highly expressed in a variety of immune cells. However, it remains unclear whether and how these variants promote inflammatory responses that influence actual disease risk. Our recent research has focused on the non-cell autonomous role of PD related genes; to investigate inflammatory and metabolic changes, we combine in vivo models with transgenic mice and in vitro systems, including patient blood cells as well as myeloid precursors and microglia differentiated from human iPSCs.
LYSOSOMAL BIOLOGY OF PARKINSON'S DISEASE
Lysosomal storage diseases (LSDs) are a group of rare, inherited, metabolic disorders caused by the deficiency of various lysosomal enzymes and the accumulation of their substrates. Most affect the brain, with variable manifestations, from mild adult-onset symptoms to severe neurodegeneration causing premature death. Interestingly, LSDs share pathological features with common neurodegenerative diseases. Thus, models of these rare conditions could greatly contribute to an enhanced understanding of more common neurodegenerative disorders, including PD and AD. Our research aims at investigating the risk/resilience factors of neuronopathic LSDs combining iPSC 2/3D models with single cell -omics.
INFECTIONS, CHRONIC INFLAMMATORY DISEASES, AND NEURODEGENERATION
Certain mutations that modulate the risk for infections also contribute to an increased predisposition for developing neurodegenerative diseases. In the framework of this project, we are investigating how specific disease-related genetic traits can confer both susceptibility to infection and predisposition to neurodegeneration. The major goal of our research is to unravel unique and shared molecular pathways underlying inflammatory, infectious, and neurodegenerative diseases. To this end, we employ in vivo modeling, stem cell-derived organoids, and functional genomic approaches.
Vasiliki joined the lab as a visiting PhD student from the University of Patras in 2017. Her PhD focused on the role of the immune system in Parkinson's disease. After successfully obtaining her PhD (2019), Vasiliki joined the lab as a postdoctoral research associate. Her current work focuses on shared mechanisms among infections, chronic inflammatory diseases, and Parkinson's disease. She employs human iPSC, brain and intestinal organoids, and scRNA-sequencing.
MARÍA JOSÉ PÉREZ J.
EMBO Long-Term Postdoctoral Fellow
María José received her PhD in Biomedical Science at the Universidad Autónoma de Chile (2018). Her PhD work focused on mitochondria biology in neurodegenerative diseases.
María José joined the lab as a postdoctoral research associate in early 2019 supported by a DAAD scholarship and a postdoctoral fellowship by the Chilean government. She then successfully obtained an EMBO longterm postdoctoral fellowship. María José will study the role of mitochondrial proteostasis in health and disease using cerebral organoids and single-cell sequencing approaches.
Francesca is completing her PhD at the university of Genova where she has been studying the inflammatory role of astrocytes in ALS. She will join our lab in March 2020 to work on a ERA-NET funded project aimed at dissecting the role of immune cell metabolism in ALS. She will employ patient iPSCs and cerebral organoids.
Pascale received her Bachelor in Biology at Bangor University in Wales and a Master in Neuroscience at King’s College London. Pascale joined the lab for her PhD in 2016 to work on the role of GBA1 in Parkinson's disease. She employs iPSCs, CRISPR-Cas9 genome editing and LC-MS.
Daria is a doctoral candidate at the university of Bologna in the laboratory of Prof. Andrea Pession. She joined the lab in 2019 to complete her PhD studies to work on inflammatory pathways involved in Gaucher Disease. She employs patient macrophages, CRIPSR-Cas9 genome editing in human iPSCs and brain organoids.
Marvin received his Master’s degree at the University of Pavia (2019). He worked in the Prion neurobiology laboratory under the supervision of Professor Roberto Chiesa (Istituto di Ricerche Farmacologiche Mario Negri, Milan), focusing on the development of new drugs for prion diseases. He joined the lab in 2019 supported by an Erasmus scholarship to work on the role of a-synuclein toxicity in GBA1 iPSC-derived neurons and brain organoids.
Stefanie completed her studies at the KIT and then joined our group in 2019 as a research assistant/lab manager. She is providing technical assistance for all the on-going projects and ensuring the smooth running of the lab.
Claudio is a visiting PhD student studying he role of mitochondrial proteostasis in health and disease using cerebral organoids.
Michela Deleidi has a strong background in neuroscience, immunology, and stem cell biology. She completed her studies in Medicine and clinical residency in Neurology at Vita-Salute University, San Raffaele Hospital (Milan, Italy). Afterwards, she worked at Harvard Medical School where she focused on the molecular mechanisms of neurodegeneration in Parkinson's disease (PD) and the use of induced pluripotent stem cells (iPSCs) for disease modeling and regenerative medicine applications. In 2011 she was awarded a research fellowship by the Alexander von Humboldt Foundation to conduct her doctoral studies at the Department of Parkinson Genetic at the University of Tübingen. During these years, she worked on the link between lysosomal storage diseases and PD using stem cell-based modeling systems.
In 2016 she has been awarded a Helmholtz Young Investigator award. Currently, she is an independent Helmholtz Investigator Group Leader at the DZNE Tübingen and Assistant Professor of Neurology at the University of Tübingen. Her research aims at tackling the cell type-specific effect of genetic variants involved in both sporadic and genetic PD, with a focus on the role of innate immunity as an early trigger of PD.
Silvia De Cicco, PhD student 2016-2020, now postdoctoral associate at BioMed X, Heidelberg.
Dina Ivanyuk, PhD student and Postdoctoral fellow 2016-2020
David Schöndorf, PhD student 2016-2019, now senior scientist at Abbvie.
Benedikt Hölbling, Master in Cellular and Molecular Neuroscience 2018, now PhD student at DRI UCL, London.
Vasileios Kampanis, Master in Cellular and Molecular Neuroscience 2017, now PhD student at University of Heidelberg.
Lukas Kristoffer Schwarz, research assistant, now Senior Technician of Immunology/uniQure Amsterdam.
Panagiotakopoulou V, De Cicco S, Ivanyuk D, Haq W, Arsic A, Yu C, Messelodi D, Oldrati M, Schöndorf DC, Perez MJ, Cassatella RP, Jacobi M, Schneiderhan-Marra N, Nikic I, Gasser T, Deleidi M*. " Interferon-γ signaling synergizes with LRRK2 in human neurons and microglia". Nat Communications, in press.
Perez MJ, Provenzano F, Deleidi M*. "Redefining microglial identity in health and disease at single-cell resolution". Review, Trends in Molecular Medicine. In press.
Ivanyuk D, Perez MJ, Panagiotakopoulou V, Di Napoli G, Brunetti D, Al-Shaana R, Kaeser S, Jucker M, Zeviani M, Viscomi C, Deleidi M*. "Loss of function of the mitochondrial peptidase PITRM1 induces proteotoxic stress and Alzheimer’s disease-like pathology in human cerebral organoids". Mol Psychiatry. 2020 Jul 7. doi: 10.1038/s41380-020-0807-4.
Armento A, Honisch S, Panagiotakopoulou V, Sonntag I, Jacob A, Kilger E, Deleidi M, Clark S, Ueffing M. "Loss of Complement Factor H impairs antioxidant capacity and energy metabolism of human RPE cells". Sci Rep. 2020 Jun 25;10(1):10320. doi: 10.1038/s41598-020-67292-z.
P. Baden, C. Yu, M. Deleidi*. "Insights into GBA Parkinson's disease pathology and therapy with induced pluripotent stem cell model systems". Review. Neurobiology of Disease. 2019 Jan 31. pii: S0969-9961(19)30032-4. doi: 10.1016/j.nbd.2019.01.023.
Compagnoni GM, Kleiner G, Samarani M, Aureli M, Faustini G, Bellucci A, Ronchi D, Bordoni A, Garbellini M, Salani S, Fortunato F, Frattini E, Abati E, Bergamini C, Fato R, Tabano S, Miozzo M, Serratto G, Passafaro M, Deleidi M, Silipigni R, Nizzardo M, Bresolin N, Comi GP, Corti S, Quinzii CM, Di Fonzo A. "Impaired autophagy and mitochondrial dysfunction in iPSC-derived dopaminergic neurons of Multiple System Atrophy". Stem Cell Rep.2018 Nov 13;11(5):1185-1198. doi: 10.1016/j.stemcr.2018.09.007.
Schöndorf DC, Ivaniuk D, Sanchez-Martinez A, Giunta I, Yu C, De Cicco S, Schwarz LK, Nestel S, Keatinge M, Pruszak J, Bandmann O, Heimrich B, Gasser T, Whitworth AJ, Deleidi M. "Nicotinamide riboside rescues mitochondrial defects and neurodegeneration in iPSC and fly models of Parkinson’s disease". Cell Rep.2018 Jun 5;23(10):2976-2988. doi: 10.1016/j.celrep.2018.05.009.
Marrone L, Bus C, Schöndorf D, Fitzgerald F, Kübler M, Schmid B, Reinhardt P, Deleidi M, Levin T, Meixner A, Klink B, Glatza M, Gloeckner CJ, Gasser T, Sterneckert J. "Generation of iPSCs stratified for a common LRRK2 risk allele for in vitro modeling of idiopathic Parkinson's disease". PLoS One. 2018 Mar 7;13(3):e0192497. doi: 10.1371/journal.pone.0192497.
Straniero L, Soldà G, Rimoldi V, Samarani M, Goldwurm S, Di Fonzo A, Kruger R, Deleidi M, Aureli M, Duga S, Asselta R. "The GBAP1 pseudogene acts as a competing endogenous RNA for the Parkinson-related gene GBA by sponging miR-22-3p". Sci Rep. 2017 Oct 5;7(1):12702. doi: 10.1038/s41598-017-12973-5.
Khurana V, Peng J, Chung CY, Auluck PK, Fanning S, Tardiff DF, Bartels T, Koeva M, Eichhorn SW, Benyamini H, Lou Y, Nutter-Upham A, Baru V, Freyzon Y, Tuncbag N, Costanzo M, San Luis BJ, Schöndorf DC, Barrasa MI, Ehsani S, Sanjana N, Zhong Q, Gasser T, Bartel DP, Vidal M, Deleidi M, Boone C, Fraenkel E, Berger B, Lindquist S. "Genome-scale networks link neurodegenerative disease genes to alpha-synuclein through specific molecular pathways". Cell Syst. 2017 Jan 25. pii: S2405-4712(16)30445-8.
Deleidi M*, Yu C. Genome editing in pluripotent stem cells: research and therapeutic applications. Biochem Biophys Res Commun.2016 Feb 27.
Baden P, Deleidi M. Mitochondrial Antigen Presentation: A vacuolar Path to Autoimmunity in Parkinson's Disease. Trends Immunol.2016 Nov;37(11):719-721. doi: 10.1016/j.it.2016.08.016.
Hallett PJ, Deleidi M, Astradsson A, Smith GA, Cooper O, Osborn TM, Sundberg M, Moore MA, Perez-Torres E, Brownell AL, Schumacher JM, Spealman RD, Isacson O. "Successful Function of Autologous iPSC-Derived Dopamine Neurons following Transplantation in a Non-Human Primate Model of Parkinson's Disease". Cell Stem Cell.2015 Mar 5;16(3):269-74.
Deleidi M*, Jäggle M and Rubino R. "Immune ageing, dysmetabolism and inflammation in neurological diseases". Front Neurosci. 2015 Jun 3;9:172.
Orack JC, Deleidi M, Pitt D, Mahajan K, Nicholas JA, Boster AL, Racke MK, Comabella M, Watanabe F, Imitola J. "Modeling Multiple Sclerosis with Stem Cell Biological Platforms: Toward functional validation of cellular and molecular phenotypes". Stem Cells Transl Med. 2015 Jan 15. pii: sctm.2014-0133.
Schöndorf DC, Aureli M, McAllister FE, Hindley CJ, Mayer F, Schmid B, Sardi SP, Valsecchi M, Hoffmann S, Schwarz LK, Hedrich U, Berg D, Shihabuddin LS, Hu J, Pruszak J, Gygi SP, Sonnino S, Gasser T*, Deleidi M*. "iPSC-derived neurons from GBA1-associated Parkinson's disease patients show autophagic defects and impaired calcium homeostasis". Nat Commun.2014 Jun 6;5:4028. * Corresponding author.
Turaç G, Hindley CJ, Thomas R, Davis JA, Deleidi M, Gasser T, Karaöz E, Pruszak J. "Combined Flow Cytometric Analysis of Surface and Intracellular Antigens Reveals Surface Molecule Markers of Human Neuropoiesis". Plos One. 2013 Jun 24;8(6):e68519.
Get in touch to learn more.
We are seeking highly motivated basic researchers and clinician scientists at all stages of their careers. If you are excited about our research send your application to Dr. Michela Deleidi at firstname.lastname@example.org
In your email, include the following items:
Cover letter including a short summary of your research interests and major achievements
A list of three contact references
Postdoctoral Researcher in Human Brain Organoids and Neurodegeneration
We are seeking highly motivated, successful, and creative individual(s) with a background in neuroscience, stem cell biology, and (neuro)-immunology.The successful applicant will work in a highly stimulating environment to pursue an exciting visionary cross-disciplinary project aimed at unraveling neuro-immune interactions in Parkinson's disease by means of patient stem cell-derived organoids. The study will involve wide range of techniques including stem cell culture, microglia differentiation, organoid generation, and scRNA sequencing. The candidate will have the opportunity to grow independently and get involved in other exciting projects, including developments of chimeric mouse models with human neurons, and glial cells; development of stem cell based therapies for degenerative disease and brain regeneration studies.
The ideal candidate should have:
Ph.D. and/or M.D. or equivalent degree in neuroscience, biology or any related field
Outstanding record of achievements from prior training
Excellent communication and interpersonal skills
The successful candidate should have prior experience in at least two of the following scientific fields:
Stem cell biology in particular experience using induced pluripotent stem cells and organoids
Next-generation sequencing and bioinformatics
To apply, please email your CV and a cover letter summarizing your research experience and interest along with the contact information of three references to: Michela Deleidi (email@example.com)
We look for a highly enthusiastic and manually skilled research technician to participate in our research toward understanding the pathogenic mechanisms of gene mutations in the pathogenesis of Parkinson' s disease by using induced pluripotent stem cells. The successful candidate should have prior experience in mammalian cell culture and molecular biology techniques. The individual will perform a variety of techniques that are necessary to generate, maintain and differentiate human induced pluripotent stem cells and perform gene editing in human stem cells. This will include the culture of mammalian cells, virus production, immunocytochemistry, western blotting, molecular cloning, PCR and confocal imaging. We have build state-of-the-art molecular and cell biological facilities including imaging, genome, and transcriptome sequencing possibilities. Essential qualities required include good organizational skills, fluency in English, a strong team spirit and time management skills.
Applications including motivation letter, CV, publication list (if applicable) and two recommendation letters or references should be sent to the contact person, Michela Deleidi (firstname.lastname@example.org)
Otfried-Müller. Str 23