Beltrán Lab – Single-cell Genomics
Multiple sclerosis is a disease affecting the central nervous system where the immune system is involved in its pathogenesis. Both the nervous and immune system represent the most daunting example of complexity in biology. Despite considerable research efforts, the knowledge and understanding of the interaction between these two complex systems and the cause of multiple sclerosis is still unknown. Gene expression analysis on bulk populations of immune cells and bulk tissue have been heretofore performed in attend to delineate the transcriptome changes in the disease. Nonetheless, in this type of analysis the differences in gene expression and variability between the different players (single cells) involved in this complex disease will remain masked.
The rapid development of single-cell analysis has revolutionized our ability to study the complexity of both the immune and nervous system at the single cell level. Individual cells are now classified by their transcriptome rather than by expression of classical cell type markers. Using state-of-the-art single-cell genomics methods, such as single-cell RNA sequencing (scRNA-seq), we identify, until now, unknown cell phenotypes and cell-cell interactions making use of unbiased bioinformatics methods. Overall, this allows us to gain deeper insights into the complexity of multiple sclerosis, as well as other complex neuroimmunological diseases.
Hiltensperger M, Beltrán E, Kant R, Tyystjärvi S, Lepennetier G, Domínguez Moreno H, Bauer IJ, Grassmann S, Jarosch S, Schober K, Buchholz VR, Kenet S, Gasperi C, Öllinger R, Rad R, Muschaweckh A, Sie C, Aly L, Knier B, Garg G, Afzali AM, Gerdes LA, Kümpfel T, Franzenburg S, Kawakami N, Hemmer B, Busch DH, Misgeld T, Dornmair K, Korn T. Skin and gut imprinted T helper cell subsets exhibit distinct functional phenotypes in CNS autoimmunity. Nat Immunol. 2021 Jul;22(7):880-892.
Brändle S, Cerina M, Weber S, Held K, Menke AF, Alcalá C, Gebert D, Herrmann AM, Pellkofer H, Gerdes LA, Bittner S, Leypoldt F, Teegen B, Komorowski L, Kümpfel T, Hohlfeld R, Meuth SG, Casanova B, Melzer N*, Beltrán E*, Dornmair K*. Cross-reactivity of a pathogenic autoantibody to a tumor antigen in GABAA receptor encephalitis. PNAS. 2021 Mar 2;118(9):e1916337118
Jafari M, Schumacher AM, Snaidero N, Ullrich Gavilanes EM, Neziraj T, Kocsis-Jutka V, Engels D, Jürgens T, Wagner I, Flórez Weidinger JD, Schmidt SS, Beltrán E, Hagan N, Woodworth L, Ofengeim D, Gans J, Wolf F, Kreutzfeldt M, Portugues R, Merkler D, Misgeld T, Kerschensteiner M. Phagocyte-mediated synapse removal in cortical neuroinflammation is promoted by local calcium accumulation. Nat Neurosci. 2021 Mar;24(3):355-367
Beltrán E, Paunovic M, Gebert D, Cesur E, Jeitler M, Höftberger R, Malotka J, Mader S, Kawakami N, Meinl E, Bradl M, Dornmair K, Lassmann H. Archeological neuroimmunology: resurrection of a pathogenic immune response from a historical case sheds light on human autoimmune encephalomyelitis and multiple sclerosis. Acta Neuropathol. 2021 Jan;141(1):67-83. doi: 10.1007/s00401-020-02239-2. Epub 2020 Oct 29.
Bracher A, Alcalá C, Ferrer J, Melzer N, Hohlfeld R, Casanova B, Beltrán E*, Dornmair K*. An expanded parenchymal CD8+ T cell clone in GABAA receptor encephalitis. Ann Clin Transl Neurol. 2020 Feb;7(2):239-244
Gross CC, Meyer C, Bhatia U, Yshii L, Kleffner I, Bauer J, Tröscher AR, Schulte-Mecklenbeck A, Herich S, Schneider-Hohendorf T, Plate H, Kuhlmann T, Schwaninger M, Brück W, Pawlitzki M, Laplaud DA, Loussouarn D, Parratt J, Barnett M, Buckland ME, Hardy TA, Reddel SW, Ringelstein M, Dörr J, Wildemann B, Kraemer M, Lassmann H, Höftberger R, Beltrán E, Dornmair K, Schwab N, Klotz L, Meuth SG, Martin-Blondel G, Wiendl H, Liblau R. CD8+ T cell-mediated endotheliopathy is a targetable mechanism of neuro-inflammation in Susac syndrome. Nat Commun. 2019 Dec 18,10(1):5779
Beltrán E, Gerdes LA, Hansen J, Flierl-Hecht A, Krebs S, Blum H, Ertl-Wagner B, Barkhof F, Kümpfel T, Hohlfeld R, Dornmair K. Early adaptive immune activation detected in monozygotic twins with prodromal multiple sclerosis. J Clin Invest. 2019 Nov 1;129(11):4758-4768.
Konjevic Sabolek M, Held K, Beltrán E, Niedl AG, Meinl E, Hohlfeld R, Lassmann H, Dornmair K. Communication of CD8+ T cells with mononuclear phagocytes in multiple sclerosis. Ann Clin Transl Neurol. 2019 Jul;6(7):1151-1164.
Souren N, Gerdes LA, Lutsik P, Gasparoni G, Beltrán E, Salhab A, Kümpfel T, Weichenhan D, Plass C, Hohlfeld R, and Walter J. DNA methylation signatures of monozygotic twins clinically discordant for multiple sclerosis. Nat Commun. 2019 May 7,10(1):2094
Beltrán E, Nguyen XH, Quériault C, Barateau L, Dauvilliers Y, Dornmair K, Liblau RS. Shared T cell receptor chains in blood memory CD4+ T cells of narcolepsy type 1 patients. J Autoimmun. 2019 Jun;100:1-6.
Spadaro M, Winklmeier S, Beltrán E, Macrini C, Höftberger R, Schuh E, Thaler F, Gerdes LA, Laurent S, Gerhards R, Brändle S, Dornmair K, Breithaupt C, Moser M, Krishnamoorthy G, Kamp F, Jenne D, Hohlfeld R, Kümpfel T, Lassmann H, Kawakami N, Meinl E. Pathogenicity of human antibodies against myelin oligodendrocyte glycoprotein. Ann Neurol. 2018 Aug,84(2):315-328
Obermeier B, Beltrán E, Hohlfeld R, Dornmair K. Molecular characterization of paired immunoglobulin heavy and light chains of clonally expanded antibodies in the presence of a strong polyclonal background. Protocol Exchange 2017, 10.1038/protex.2017.113
Gerdes LA*, Held K*, Beltrán E*, Berking C, Prinz JC, Junker A, Tietze JK, Ertl-Wagner B, Straube A, Kümpfel T, Dornmair K, Hohlfeld R. CTLA4 as Immunological Checkpoint in the Development of Multiple Sclerosis. Ann Neurol. 2016 Aug, 80(2): 294-300
Held K, Beltrán E, Moser M, Hohlfeld R, Dornmair K. T-cell receptor repertoire of human peripheral CD161hiTRAV1-2+ MAIT cells revealed by next generation sequencing and single cell analysis. Hum Immunol. 2015 Sep, 76(9): 607-14
Held K, Bhonsle-Deeng L, Siewert K, Sato W, Beltrán E, Schmidt S, Rühl G, Ng JKM, Engerer P, Moser M, Klinkert WEF, Babbe H, Misgeld T, Wekerle H, Laplaud DA, Hohlfeld R, Dornmair K. αβ T-cell receptors from multiple sclerosis brain lesion show MAIT cell-reladed features. Neurol Neuroimmunol Neuroinflamm. 2015 Aug, 2(4): e107
Beltrán E, Obermeier B, Moser M, Coret F, Simó-Castelló M, Boscá I, Pérez-Miralles F, Villar LM, Senel M, Tumani H, Hohlfeld R, Casanova B, Dornmair K. Intrathecal somatic hypermutation of IgM in multiple sclerosis and neuroinflammation. Brain. 2014 Oct;137(Pt 10):2703-14.
Klara Magdalena Eglseer,
I grew up in Austria and moved to Munich to study medicine in 2017. Due to my special interest in neurology and genetics, I joined the lab in May 2021. My project focusses on the progressive phase of multiple sclerosis, observing gene expression patterns of immune cells on a single cell level. This includes the bioinformatics analysis of big datasets, which I really enjoy.
Outside of the lab I play piano, sing in a choir and love being in the mountains as often as possible.
I originally come from Ukraine and started my medical studies at the LMU Munich in 2016. I am passionate about neurosciences and immunology, but if you ask me about my favourite cells in the human body, I would answer without hesitation: CD8+ T cells. Using novel multiomic approaches, such as single-cell RNA and TCR-sequencing, I am gaining a deeper insight into the pathogenesis and development of multiple sclerosis and its different subtypes. With the help of cutting-edge techniques, such as laser capture microdissection and subsequent whole-transcriptome sequencing I can reach even a single-cell resolution by preserving both spatial and RNA-based information. The constant development of our tools and techniques plays an exceedingly important part for our research, which is why our team is always updating our bioinformatics pipelines to perform our research on the highest level.
In my spare time, I am voluntarily involved in the organisation of tutorials for medical students in Ukraine. I also enjoy playing the guitar, cooking and cycling.
Since I started medical school in 2017 I am interested in neuroscience. The many unknowns that need to be explored to understand the complexity of the nervous system fascinate me immensely. As my interest in biochemical processes grew, so did my enthusiasm for immunology. After attending additional courses in 'molecular biotechnology' I realized the relevance of bioinformatics for future innovative options. Neuroimmunologic research now offers an unique combination of my fields of interest. With the support of the medMS programme of the Hertie Foundation, I am very grateful to be able to implement my doctoral thesis under the supervision of PD Dr. Gerdes and Dr. Beltrán at the Institute of Neuroimmunology of the LMU. The establishment of a new technique, the sc-ATAC seq, will be the focus along with other projects and I hope to gain deeper insight into the complexity of autoimmune diseases of which MS serves as a prototype.
As an alternate way of studying at a university, I completed an education as "biological technical assistant (BTA) at "Chemieschule Dr. Erwin Elhardt" in Munich. However, this didn’t stop me from doing more complex lab techniques which are usually done by academics. I started at the Helmholtz Center in Munich, where I was hired for a cooperation project with ROCHE. Inspired by the flow cytometry principle and applications, I soon applied for a job as an administrator and assistant for the cell sorting facility at the "TranslaTUM". Together with my supervisors we successfully supported many projects by analyzing and sorting a wide variety of cell types.
In 2020 I joined the team of Dr. Eduardo Beltrán. Here I got the great opportunity to extend my knowledge in many areas: handling of CSF and blood samples from patients suffering from Multiple Sclerosis, in which I perform single-cell capture by 10x Genomics, sample barcoding, cDNA amplification and library preparation. After sequencing I learned how to analyse such a gigantic data output using bioinformatics tools. With my 7 year experience in flow cytometry cell sorting I'm always happy to support my team on the FACS Aria Fusion.
In my free time, I go swimming, cycling or DYI (Do it yourself). But mostly I spend it with my awesome wife and son.
Tandem Team with:
Dr. rer. nat. Eduardo Beltrán
I consider myself a symbiont between molecular biologist and bioinformatician. This symbiosis started during my first postdoc in Munich out of necessity, due to the enormous impact of next-generation sequencing in life sciences and biomedical research. Today, I strive to maintain the most advanced expertise in single cell genomics and data analysis to understand these high-volume data sets in the hopes of gaining more information and unravelling complex diseases. My main research topic is the study of neuroimmunological diseases, and the role of CD8 T cells in multiple sclerosis as my main focus.
2000 – 2005 Biology Diploma, University of Valencia, Spain
2006 – 2010 PhD program at Príncipe Felipe Research Center and University of Valencia, Spain (summa cum laude)
2011 Postdoctoral fellow at the Max Planck Institute of Neurobiology, Martinsried, Germany
2012 Postdoctoral fellow at the Dept. of Multiple Sclerosis, Medical Research Institute Hospital La Fe, Valencia, Spain
Academic positions & appointments
2013 – 2020 Research associate at the Institute of Clinical Neuroimmunology (AG Dornmair), LMU Munich, Germany
since 2021 Hub group leader of the Single-cell Transcriptomic Hub at the DFG-funded Excellence Cluster “Munich Cluster for Systems Neurology” (SyNergy)
since 2021 Group leader at the the Institute of Clinical Neuroimmunology, Biomedical Center of the LMU Munich, Germany
Awards & honors
2021 Outstanding Publication Award from the Rosa Laura and Hartmut Wekerle foundation
2018 Young Investigator Grant from the “Verein zur Förderung von Wissenschaft und Forschung” of the Faculty of Medicine at LMU Munich
2016 Young Investigator Grant from the “Friedrich-Baur-Stiftung”
2012 ENS (European Neurology Society) fellowship
2011 EMBO (European Molecular Biology Organization) fellowship
2009 NENS Exchange Grant for "Laser-capture microdissection” at Max Planck Institute for Experimental Medicine, Göttingen, Germany
DoktaMed 2020 – and the winner is… Vlad!
Houston, we have an "ERROR"!
Celebrating my Award in Corona...