Neuroimmunology Munich

Research Focus

In monozygotic twins the estimated concordance rate for MS rate is around 25%; hence 75% of twin pairs are clinically discordant (i.e. only one twin sibling is affected with MS, whereas the co-twin is seemingly healthy). This suggests that although the genetic background plays a strong role, environmental factors are also important. Presumably genetic and environmental risk factors do not act independently, but are interactive. A well-established approach that helps to disentangle genetic and environmental risk factors relies on monozygotic twins. Specifically, studying monozygotic MS-discordant twins allows us to identify factors that differ between cases and controls who are not only matched for age, gender and genetic background, but also matched for a broad range of (early) environmental factors.

For this purpose, 2012 I started assembling the national MS TWIN STUDY at the Institute of Clinical Neuroimmunology, LMU Munich. So far, I have been recruiting a still expanding cohort of already 85 monozygotic twin pairs who are clinically discordant for MS at study entry. The MS TWIN STUDY offers great advantages to approach a broad spectrum of MS related research questions as a discovery cohort and important reference. The MS TWINS COHORT is a high risk cohort and to date we detected that about 20% of the clinically healthy co-twins in our cohort have paraclinical (MRI and/or CSF) signs of subclinical neuroinflammation (SCNI). This prodromal stage is still enigmatic and we try to closely monitor these co-twins to get a glimpse into relevant triggering factors during the earliest phases of MS.

The MS TWIN STUDY is continuously recruiting and expanding including longitudinal follow up.

Building upon our CSF single cell sequencing results we are currently running additional experiments in CSF and blood to consolidate and expand our findings taking into account prodromal stages as well as different disease courses.

Based upon our previous work on the gut microbiome we are currently validating our initial results with the analysis of a larger sample set. In addition we focus now on the proximal gut microbiome of the small intestine, since we believe this might be the immunological hot spot. For this approach colonoscopies up to the terminal ileum are performed and we will process these samples for microbial profiling as well as additional transfer experiments into germ-free mice.

Since we have detected relevant epigenetic modifications we want to build upon these findings and perform a reanalysis of the whole cohort including follow-up samples in combination with a refined analysis using different approaches.

The MS TWIN STUDY offers a chance to provide insights into important sociodemographic issues that are so far insufficiently addressed in the MS field, such as impact on cost and burden of the disease, quality of life, mood, as well the current Covid-19-pandemic. For that purpose we have rolled out a large questionnaire that we are currently evaluating.

The MS TWIN STUDY is a high risk cohort and hence the analysis of possible prodromal signs, such as cognitive decline or OCT (optical coherence tomography as a surrogate of neurodegeneration) markers are currently addressed with the implementation of detailed neuropsychological testing as well as OCT investigation into our assessment.

PODCAST-links

AMBOSS podcast für Medizinstudenten und Ärzte

MS Perspektive-der Multiple Sklerose Podcast

MS im Fokus mir Dr. Adrian-Minh Schumacher

VIDEO-Links:

Summit 2022 Joint Session - fellows & friends (fellows-ghst.de)

Publications

Broader Epstein–Barr virus–specific T cell receptor repertoire in the MS TWIN STUDY

September 2022- Epstein–Barr virus (EBV) infection precedes multiple sclerosis (MS) pathology and cross-reactive antibodies might link EBV infection to CNS autoimmunity. As an altered anti-EBV T cell reaction was suggested in MS, in collaboration with the Institute of Translational Neurology in Münster, we queried peripheral blood T cell receptor β chain (TCRβ) repertoires in 35 monozygotic, MS-discordant twin pairs and larger control groups for multimer-confirmed, viral antigen–specific TCRβ sequences. We detected more MHC-I–restricted EBV-specific TCRβ sequences in MS patients. In MS patients, cerebrospinal fluid also contained EBV-specific central memory CD8+ T cells, suggesting recent priming. Therefore, MS is not only preceded by EBV infection, but also associated with broader EBV-specific TCR repertoires, consistent with an ongoing anti-EBV immune reaction in MS.

Schneider-Hohendorf T*, Gerdes LA*, Pignolet B, Gittelman R, Ostkamp P, Rubelt F, Raposo C, Tackenberg B, Riepenhausen M, Janoschka C, Wünsch C, Bucciarelli F, Flierl-Hecht A, Beltrán E, Kümpfel T, Anslinger K, Gross CC, Chapman H, Kaplan I, Brassat D, Wekerle H, Kerschensteiner M, Klotz L, Lünemann JD, Hohlfeld R, Liblau R, Wiendl H, Schwab N. Broader Epstein-Barr virus-specific T cell receptor repertoire in patients with multiple sclerosis.J Exp Med. 2022;219(11):e20220650.

Twin effect overrides disease specific immune signatures

September 2020 – In this study we used our unique setting of the MS TWIN STUDY to explore the peripheral immune signature in collaboration with the UK Münster. In each twin pair, the immune signatures were remarkably similar, pointing to a strong influence of shared genetic and environmental factors. However, when we focused on a subgroup of seemingly healthy cotwins who showed subtle signs of “subclinical neuro-inflammation,” we identified a distinct signature of memory T cells.
Press Release
Commentary

Gerdes LA, Janoschka C, Eveslage M, Mannig B, Wirth T, Schulte-Mecklenbeck A, Lauks S, Glau L, Gross CC, Tolosa E, Flierl-Hecht A, Ertl-Wagner B, Barkhof F, Meuth SG, Kümpfel T, Wiendl H, Hohlfeld R, Klotz L. Immune signatures of prodromal multiple sclerosis in monozygotic twins. Proc Natl Acad Sci U S A. 2020 Sep 1;117(35):21546-21556.

Altered lipid signaling in plasma of MS co-twins

September 2020 –The search for a blood biomarker of MS has ever been the goal of many researchers since it might provide a better understanding of the pathophysiology as well as enable disease monitoring. For this aim, we performed quantitative shotgun lipidomics on the plasma of 73 pairs of our MS TWIN COHORT. We analyzed 243 lipid species, evaluated lipid features, and detected phospholipids that were significantly altered in the plasma of co-twins with MS compared to their non-affected siblings. Strikingly, changes were most prominent in ether phosphatidylethanolamines and ether phosphatidylcholines, suggesting a role for altered lipid signaling in the disease.

Penkert H, Lauber C, Gerl MJ, Klose C, Damm M, Fitzner D, Flierl-Hecht A, Kümpfel T, Kerschensteiner M, Hohlfeld R, Gerdes LA, Simons M. Plasma lipidomics of monozygotic twins discordant for multiple sclerosis. Ann Clin Transl Neurol. 2020 Nov 7. Epub ahead of print.

DNA methylation signatures are associated with MS phenotype

May 2019 – The modest concordance rate for MS in monozygotic twins strongly argues for involvement of epigenetic factors. To check the contribution of epigenetic modifications we looked at the methylomes of 45 pairs from the MS TWIN STUDY together with our collaborators Nicole Souren and Jörn Walter, Saarland Universtiy. We identified seven MS-associated differentially methylated positions (DMPs) of which we validated two, including a region in the TMEM232 promoter and ZBTB16 enhancer. Not expected but not of less relevance we presented epigenetic biomarkers for current interferon-beta treatment, and that the ZBTB16 DMP is a signature for prior glucocorticoid treatment. Taken together, this study represents an important reference for epigenomic MS studies, identifies new candidate epigenetic markers, and highlights treatment effects and genetic background as major confounders.
Press Release

Souren NY, Gerdes LA, Lutsik P, Gasparoni G, Beltrán E, Salhab A, Kümpfel T, Weichenhan D, Plass C, Hohlfeld R, Walter J. DNA methylation signatures of monozygotic twins clinically discordant for multiple sclerosis. Nat Commun. 2019 May 7;10(1):2094.

Detection of early adaptive immune activation in prodromal MS

November 2019 – The early immunological events that drive MS are still enigmatic. To add a piece to the jigsaw we analyzed CSF samples of a unique selection of our MS TWIN STUDY. Using single-cell RNA sequencing we identified clonally expanded CD8+ T cells, plasmablasts, and, to a lesser extent, CD4+ T cells not only from MS co-twins but also from clinical healthy co-twins with signs of subclinical neuroinflammation as detected on MRI and/or CSF. Strikingly, clonally expanded T cells showed characteristics of activated tissue-resident memory T (TRM) cells and were already detectable in prodromal stages but more pronounced in patients with definite MS. Our data provide evidence for very early concomitant activation of 3 components of the adaptive immune system in MS, with a notable contribution of clonally expanded TRM-like CD8+ cells.
Press Release

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.

What´s it got to do with our guts? A possible link between the gut microbiome and MS!

August 2017 – Studies using experimental models have indicated that MS like disease can be triggered in the gut following interactions of brain autoimmune T lymphocytes with local microbiota. In this key paper, we studied the composition of the gut microbiota in our MS TWIN STUDY and in addition transferred human-derived microbiota into transgenic mice expressing a myelin autoantigen-specific T cell receptor. Strikingly, we detected that gut microbiota from MS-affected twins induced CNS-specific autoimmunity at a higher incidence than microbiota from healthy co-twins. Our results offered functional evidence that human microbiome components contribute to CNS-specific autoimmunity and opened up the field for further studies of the gut microbiome in MS.
Press Release
Awarded for highlights of MPG Research 2017

Berer K, Gerdes LA, Cekanaviciute E, Jia X, Xiao L, Xia Z, Liu C, Klotz L, Stauffer U, Baranzini SE, Kümpfel T, Hohlfeld R, Krishnamoorthy G, Wekerle H. Gut microbiota from multiple sclerosis patients enables spontaneous autoimmune encephalomyelitis in mice. Proc Natl Acad Sci U S A. 2017 Oct 3;114(40):10719-10724.

Mitochondrial DNA variation is not a major driver of MS discordance in monozygotic twins

August 2016 –Here we used the MS TWIN STUDY to approach the the debated link between mitochondrial DNA (mtDNA) variation and MS. In collaboration with Nicole Souren, Saarland University, ultra‐deep sequencing of blood‐derived mtDNA revealed 25 heteroplasmic variants with potentially pathogenic features in 18 pairs. All variants were pair‐specific and had low and/or similar heteroplasmy levels in both co-twins. Furthermore, the majority of heteroplasmic variants were shared among MZ twins and exhibited more similar heteroplasmy levels in the same tissue of MZ twins.
Our analysis yielded most important results to exclude mtDNA variation as a major driver of the discordant clinical manifestation of MS in MZ twins, and provided valuable insights into the occurrence and distribution of heteroplasmic variants within MZ twins and nonidentical siblings, and across different tissues.

Souren NY, Gerdes LA, Kümpfel T, Lutsik P, Klopstock T, Hohlfeld R, Walter J. Mitochondrial DNA Variation and Heteroplasmy in Monozygotic Twins Clinically Discordant for Multiple Sclerosis. Hum Mutat. 2016 Aug;37(8):765-75. doi: 10.1002/humu.23003. Epub 2016 May 13. PMID: 27119776.
2022

Schneider-Hohendorf T*, Gerdes LA*, Pignolet B, Gittelman R, Ostkamp P, Rubelt F, Raposo C, Tackenberg B, Riepenhausen M, Janoschka C, Wünsch C, Bucciarelli F, Flierl-Hecht A, Beltrán E, Kümpfel T, Anslinger K, Gross CC, Chapman H, Kaplan I, Brassat D, Wekerle H, Kerschensteiner M, Klotz L, Lünemann JD, Hohlfeld R, Liblau R, Wiendl H, Schwab N. Broader Epstein-Barr virus-specific T cell receptor repertoire in patients with multiple sclerosis.J Exp Med. 2022;219(11):e20220650.

Ingelfinger F, Gerdes LA, Kavaka V, Krishnarajah S, Friebel E, Galli E, Zwicky P, Furrer R, Peukert C, Dutertre CA, Eglseer KM, Ginhoux F, Flierl-Hecht A, Kümpfel T, De Feo D, Schreiner B, Mundt S, Kerschensteiner M, Hohlfeld R, Beltrán E, Becher B. Twin study reveals non-heritable immune perturbations in multiple sclerosis. Nature. 2022 Mar;603(7899):152-158.

Ingelfinger F, Beltrán E, Gerdes LA, Becher B. Single-cell multiomics in neuroinflammation. Curr Opin Immunol. 2022 Jun;76:102180.

2021

Mortazavi M, Hizarci Ö, Gerdes LA, Havla J, Kümpfel T, Hohlfeld R, Stöcklein S, Keeser D, Ertl-Wagner B. Multiple sclerosis and subclinical neuropathology in healthy individuals with familial risk: A scoping review of MRI studies. Neuroimage Clin. 2021;31:102734.

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 helper T cell subsets exhibit distinct functional phenotypes in central nervous system autoimmunity. Nat Immunol. 2021 Jul;22(7):880-892.

Brändle SM, 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. Proc Natl Acad Sci U S A. 2021 Mar 2;118(9):e1916337118.

Hohlfeld R, Beltran E, Gerdes LA, Dornmair K. Tissue-resident CD8+ memory T cells in multiple sclerosis. Brain. 2021 Feb 12;144(1):e7.

2020

Gerhards R, Pfeffer LK, Lorenz J, Starost L, Nowack L, Thaler FS, Schlüter M, Rübsamen H, Macrini C, Winklmeier S, Mader S, Bronge M, Grönlund H, Feederle R, Hsia HE, Lichtenthaler SF, Merl-Pham J, Hauck SM, Kuhlmann T, Bauer IJ, Beltran E, Gerdes LA, Mezydlo A, Bar-Or A, Banwell B, Khademi M, Olsson T, Hohlfeld R, Lassmann H, Kümpfel T, Kawakami N, Meinl E. Oligodendrocyte myelin glycoprotein as a novel target for pathogenic autoimmunity in the CNS. Acta Neuropathol Commun. 2020 Nov 30;8(1):207.

Penkert H, Lauber C, Gerl MJ, Klose C, Damm M, Fitzner D, Flierl—Hecht A, Kümpfel T, Kerschensteiner M, Hohlfeld R, Gerdes LA*, Simons M*. Plasma lipidomics of monozygotic twins discordant for multiple sclerosis. Ann Clin Trans Neurol 2020 Nov 7. (* co-senior author)

Gerdes LA, Yoon H, Peters A. Mikrobiota und Multiple Sklerose [Microbiota and multiple sclerosis]. Nervenarzt. 2020 Oct 12. German.

Gerdes LA*, Janoschka C*, Eveslage M, Mannig B, Wirth T, Schulte-Mecklenbeck A, Lauks S, Glau L, Gross CC, Tolosa E, Flierl-Hecht A, Ertl-Wagner B, Barkhof F, Meuth SG, Kümpfel T, Wiendl H, Hohlfeld R, Klotz L. Immune signatures of prodromal multiple sclerosis in monozygotic twins. Proc Natl Acad Sci USA. 2020 Sep 1;117(35):21546-21556. (* co-first author)

Völk S, Unterrainer M, Albert NL, Havla J, Gerdes LA, Schumacher M, Brendel M, Kaiser L, Adorjan K, Rupprecht R, Bartenstein P, Kümpfel T, Danek A, Völk S, et al. TSPO PET With 18F-GE-180 to Differentiate Variants of Multiple Sclerosis: Relapsing-Remitting Multiple Sclerosis, Tumefactive Demyelination, and Baló's Concentric Sclerosis. Clin Nucl Med. 2020 Oct;45(10):e447-e448.

Mulazzani E, Wagner D, Havla J, Schlüter M, Meinl I, Gerdes LA, Kümpfel T.Mulazzani E, et al. Neurological phenotypes in patients with NLRP3-, MEFV-, and TNFRSF1A low-penetrance variants. J Neuroinflammation. 2020 Jun 20;17(1):196.

Stork L, Ellenberger D, Ruprecht K, Reindl M, Beißbarth T, Friede T, Kümpfel T, Gerdes LA, Gloth M, Liman T, Paul F, Brück W, Metz I.Stork L, et al. Antibody signatures in patients with histopathologically defined multiple sclerosis patterns. Acta Neuropathol. 2020 Mar;139(3):547-564

2019

Beltran 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. (* co-first author)

Souren NY, Gerdes LA, Lutsik P, Gasparoni G, Beltrán E, Salhab A, Kümpfel T, Weichenhan D, Plass C, Hohlfeld R, Walter J. DNA methylation signatures of monozygotic twins clinically discordant for multiple sclerosis. Nat Commun. 2019 May 7;10(1):2094.

Marti Fernandez I, Macrini C, Krumbholz M, Hensbergen PJ, Hipgrave Ederveen AL, Winklmeier S, Vural A, Kurne A, Jenne D, Kamp F, Gerdes LA, Hohlfeld R, Wuhrer M, Kümpfel T, Meinl E. The Glycosylation Site of Myelin Oligodendrocyte Glycoprotein Affects Autoantibody Recognition in a Large Proportion of Patients. Front Immunol. 2019 Jun 11;10:1189.

2018

Spadaro M, Winklmeier S, Beltrán E, Macrini C, Höftberger R, Schuh E, Thaler FS, Gerdes LA, Laurent S, Gerhards R, Brändle S, Dornmair K, Breithaupt C, Krumbholz M, 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.

2017

Berer K*, Gerdes LA*, Cekanaviciute E, et al. Gut microbiota from multiple sclerosis patients enables spontaneous autoimmune encephalomyelitis in mice. Proc Natl Acad Sci U S A 2017; 114(40): 10719-24. (* co-first author)

Hartl C, Obermeier V, Gerdes LA, Brugel M, von Kries R, Kumpfel T. Seasonal variations of 25-OH vitamin D serum levels are associated with clinical disease activity in multiple sclerosis patients. J Neurol Sci 2017; 375: 160-4.

2016

Souren NY*, Gerdes LA*, Kumpfel T, et al. Mitochondrial DNA Variation and Heteroplasmy in Monozygotic Twins Clinically Discordant for Multiple Sclerosis. Hum Mutat 2016; 37(8): 765-75. (* co-first author)

Gerdes LA*, Held K*, Beltran E*, et al. CTLA4 as Immunological Checkpoint in the Development of Multiple Sclerosis. Ann Neurol 2016; 80(2): 294-300. (* co-first author)

Spadaro M*, Gerdes LA*, Krumbholz M, et al. Autoantibodies to MOG in a distinct subgroup of adult multiple sclerosis. Neurol Neuroimmunol Neuroinflamm 2016; 3(5): e257. (* co-first author)

Kumpfel T, Gerdes LA, Heck C, Pruss H. Delayed diagnosis of extraovarian teratoma in relapsing anti-NMDA receptor encephalitis. Neurol Neuroimmunol Neuroinflamm 2016; 3(4): e250.

Schankin CJ, Kastele F, Gerdes LA, et al. New-Onset Headache in Patients With Autoimmune Encephalitis Is Associated With anti-NMDA-Receptor Antibodies. Headache 2016; 56(6): 995-1003.

Sadovnick AD, Traboulsee AL, Bernales CQ, …, Gerdes LA, et al. Analysis of Plasminogen Genetic Variants in Multiple Sclerosis Patients. G3 (Bethesda, Md) 2016; 6(7): 2073-9.

2015

Spadaro M*, Gerdes LA*, Mayer MC, et al. Histopathology and clinical course of MOG-antibody-associated encephalomyelitis. Annals of clinical and translational neurology 2015; 2(3): 295-301. (* co-first author)

Schuh E, Lohse P, Ertl-Wagner B, Gerdes LA, et al. Expanding spectrum of neurologic manifestations in patients with NLRP3 low-penetrance mutations. Neurol Neuroimmunol Neuroinflamm 2015; 2(4): e109.

Schrewe L, Lill CM, Liu T, …, Gerdes LA, et al. Investigation of sex-specific effects of apolipoprotein E on severity of EAE and MS. Journal of neuroinflammation 2015; 12: 234.

Lill CM, Luessi F, Alcina A, …, Gerdes LA, et al. Genome-wide significant association with seven novel multiple sclerosis risk loci. Journal of medical genetics 2015; 52(12): 848-55.

2014

Lill CM, Schilling M, Ansaloni S, …, Gerdes LA, et al. Assessment of microRNA-related SNP effects in the 3' untranslated region of the IL22RA2 risk locus in multiple sclerosis. Neurogenetics 2014; 15(2): 129-34.

2013

Havla J, Lohse P, Gerdes LA, Hohlfeld R, Kumpfel T. Symptoms related to tumor necrosis factor receptor 1-associated periodic syndrome, multiple sclerosis, and severe rheumatoid arthritis in patients carrying the TNF receptor superfamily 1A D12E/p.Asp41Glu mutation. The Journal of rheumatology 2013; 40(3): 261-4.

Lill CM, Schjeide BM, Graetz C, …, Gerdes LA, et al. Genome-wide significant association of ANKRD55 rs6859219 and multiple sclerosis risk. Journal of medical genetics 2013; 50(3): 140-3.

Lill CM, Schjeide BM, Graetz C, …, Gerdes LA, et al. MANBA, CXCR5, SOX8, RPS6KB1 and ZBTB46 are genetic risk loci for multiple sclerosis. Brain 2013; 136(Pt 6): 1778-82.

2012

Kumpfel T, Gerdes LA, Wacker T, et al. Familial Mediterranean fever-associated mutation pyrin E148Q as a potential risk factor for multiple sclerosis. Mult Scler 2012; 18(9): 1229-38.

Team

Dr. med. Andrea Flierl-Hecht

After my studies in human medicine at the university of Freiburg and at the LMU Munich I started as a resident of neurology at the university of Erlangen-Nürnberg. In addition to my neurology training I spezialized in epileptology in the group of Prof. H. Stefan and took care of pharmacoresistant epilepsy patients, performed preoperative diagnostics as well as conducted clinical trials. I presented my research at national and international congresses. Since 2005 I got licensed as a neurologist. After I moved to the south of Bavaria I worked at the epilepsy unit at the university hospital of Ulm. In 2017, I was glad to join and support the MS TWIN STUDY with a research interest in cognition in the MS TWIN STUDY. In addition I am supporting the clinical team and the outpatient clinic and clinical trials of the Institute of clinical neuroimmunology at the LMU Munich

Vladyslav Kavaka, Medical student

I originally come from Ukraine and started my medical studies at the LMU Munich in 2016. Neurosciences in combination with immunology have always fascinated me, which is why I started my doctoral thesis in April 2020 under the supervision of PD Dr. Gerdes and Dr. Beltran, with support from the Hertie Foundation. In the course of my doctoral thesis, I am investigating multiple sclerosis (MS) and its different types. Using novel approaches, such as single-cell RNA sequencing and bioinformatic analysis of data, I am gaining a deeper insight into the pathogenesis and development of this disease. For this purpose, also the samples from a unique cohort of MS-discordant identical twins are being processed as part of the MS TWIN STUDY. In my spare time, I am involved voluntarily in the organisation of tutorials for medical students in Ukraine. I also enjoy playing the guitar, cooking and cycling.

Klara Magdalena Eglseer, Medical student

Since the beginning of my medical studies in 2017, I increasingly got captivated by neuroscience and the complex diseases of the nervous system. Driven by this interest, I started my doctoral thesis in May

2021 at the LMU and I am pleased to be supported by the medMS-program of the Hertie Foundation. Supervised by PD Dr. Gerdes and Dr. Beltran my research focusses on immunological aspects of the progressive form of multiple sclerosis, using samples from the extraordinary cohort of the MS TWIN STUDY. Working with highly topical techniques like singe-cell RNA sequencing and analysing the datasets, as well as being in contact with the probands of our study, gives me a deeper understanding of the overall picture of this autoimmune disease.

Outside of the lab I enjoy singing in the choir, playing piano and spending time in the mountains.

Luisa Mutschler,
Medical student

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.

Gabriela Shalaginova, MSc, research assistant

I studied Bioprocess-Informatics at the University of Applied Sciences Weihenstephan-Triesdorf from 2013-2017, afterwards I continued my university education and graduated 2020 with a Master of Science degree in Biotechnology/Bioengineering (HM Munich, University of Applied Science Weihenstephan). After my studies I joined the team of the MS-Twin Study at the Institute of Clinical Neuroimmunology as a research assistant, where I am currently performing the computational analysis of large data sets. This includes information from various questionnaires e.g. regarding cost and burden of disease, quality of life as well as the impact of the Covid-19 pandemic on mental health.

Dr. rer. nat. Eduardo Beltran

In a complex disease like multiple sclerosis both genetic and environmental factors are contributing to the disease. Our MS TWIN STUDY allows us to remove the environment effect from the equation. And this help us to get a clearer picture and sharper insight into the genetic contribution to the onset of the disease. By applying single-cell RNA-seq analysis in the cells of the CSF, we have been able to investigate the earliest identifiable stage of MS, which we refer to as subclinical neuroinflammation (SCNI), and identify the first changes in the transcriptome in the onset of MS.

Hongsup Yoon, Postdoc

I received my PhD at the Technical University of Munich. During my PhD training I became interested in interactions between gut microbiota and host cells in the auto-immune diseases. I joined Prof. Dr. Hartmut Wekerle and Prof. Dr. Reinhard Hohlfeld's lab as a postdoc and am currently conducting collaborative project with Lisa Ann Gerdes. As close collaborator, I am working on the MS TWIN STUDY to understand the role of gut microbiome in triggering immune response in the intestine and CNS of patients with multiple sclerosis.

I finished my medical school with a clinical focus on neurology and research experience in neuroimmunology, targeting a combination of both for my professional career I set grounds at the Institute of Clinical Neuroimmunology in 2004 under the lead of Prof. Dr. Hohlfeld. During the first decade I covered a broad spectrum of research interests ranging from characterization of genetic and environmental risk factors to blood biomarkers and novel antibodies in MS. However, with the perception of the limitations every cohort comes along with I set out to initiate the MS TWIN STUDY, which counts up to date 85 monozygotic twin pairs with discordance for MS. The twin setting comprises excellent control for genetic heterogeneity as well as a large portion of environmental risk factors and offers great advantages to study a broad range of triggering factors of MS as well as being an important reference for scientific questions. The MS TWIN STUDY challenges what I was looking for, personal, medical as well as scientific skills and hence I am grateful to be close to my target.

Education

1997 – 2001 Medical School, Ruprecht-Karls-University of Heidelberg

1999 – 2004 Dissertation magna cum laude, Department of Neurology, University Hospital Heidelberg

2001 – 2003 Medical School, University of Hamburg, Hamburg, Germany

2002 – 2003 Clinical Electives, Hamburg, Malmö, London, Institute of Neurology

Nov 2003 3. State Examination and Medical License (Approbation)

Professional Experience

Aug 2020 – present: Junior Research Group Leader, Institute of Clinical Neuroimmunology

Jan 2021 – present: Associated member Munich Cluster for Systems Neurology (SyNergy)

May 2021: Licensed Consultant of neurology

Sep 2021 – present: Consultant at Institute of Clinical Neuroimmunology (Oberärztin)

May 2022 – present: Advanced Clinician Scientist Program, Munich Cluster for Systems Neurology (SyNergy)

Dec 2022: Member of the “Ärztlicher Beirat der DMSG”

Jan 2004 – present: Physician and researcher at the Institute of Clinical Neuroimmunology and Department of Neurology, LMU Klinikum, Munich, Germany

Since 2012: Initiation and principal investigator of the MS TWIN STUDY

2016 – 2018: Psychiatry and neurology rotation at MPI of Psychiatry Munich

Dec 2018: Habilitation in Neuroimmunology, LMU Klinikum, Munich

GCP-certified study physician with participation as co-investigator and deputy in multiple Phase II and Phase III clinical trials on Multiple Sclerosis treatment. Participation in investigator meetings. Active participation in national and international congresses on Multiple Sclerosis, including several poster and platform presentation at ECTRIMS, invited talks. Regular teaching activity at Medical School LMU Klinikum Munich. Member of the German Society of Neurology (DGN).

Research Grants

2020 – present: Associated Investigator of SyNergy and Advanced Clinician Scientist Program, funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy – ID 390857198) (25.000 €/year)

2021– present: SyNergy Funding Tandem D2 (42.000 €/year)

2021: Research Grant, NMSS USA (261.000 €)

2009: Research Grant, LMU Munich

2015: Research Grant, Gemeinnützige Hertie-Stiftung

2018: Research Grant, myLab Programme Gemeinnützige Hertie-Stiftung

2020: Research Grant, DMSG

2020: Research Grant, WiFoMed Lmu Munich

2020: Research Grant, Merck

Lab Pics