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                                                            Kim-Hellmuth Lab

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                                                            Research topics

                                                            • Genetic influence on human immune response variation
                                                            • COVID-19 host genetics
                                                            • Molecular characterization of COVID-19 infections in children and young adults

                                                            Dr. med. Sarah Kim-Hellmuth

                                                            ✉ Sarah.Kimhellmuth@med.uni-muenchen.de

                                                            Genetic basis of human immune response variation

                                                            The human immune system plays an important role in host protection, autoimmune and inflammatory diseases, cancer, metabolism, and ageing. Given this central role in many human pathologies, it is crucial to understand the variability of immune responses at the population level and how this variability relates to disease susceptibility. 

                                                            Large genome-wide association studies have implicated hundreds of genetic loci in immune-related genes highlighting the immune system’s role in the biological mechanism underlying genetic risk to numerous diseases. However, for the vast majority of these genetic variants, we have little understanding of their functional effects and their context-specificity. Studying the genetic influence on immune response is further complicated by the complexity of the immune system, which consists of many different cell types that respond to a plethora of signals, interact with each other and induce different effector functions under diverse kinetics.

                                                            Our group integrates state-of-the-art genomic and functional genetic approaches to characterize the genetic basis of human immune response variation to advance our understanding of disease-associated variants and answer questions of genome function plasticity that is shaped by gene-by-environment interactions. We focus in particular on molecular quantitative traits (molQTLs) in the context of immune activation and disentangle the cell type and context specificity of functional genetic variants with the ultimate goal to develop a roadmap for complex traits at large and enable the move from genetic discovery to functional interpretation and ultimately clinical impact.

                                                            COVID-19 in children and young adults

                                                            COVID-19 is an infectious disease caused by the new strain of coronavirus SARS-CoV-2. It was first identified in 2019 in Wuhan, China, and has since spread globally, resulting in the 2019–20 coronavirus pandemic. Common symptoms include fever and cough, however disease symptoms as well as disease course and outcome are highly variable ranging from asymptomatic cases to severe pneumonia and death. While children are likely to have milder symptoms than adults, children of all ages are susceptible to COVID-19 and can suffer from severe disease. Until now it is unknown why children show a different course of disease compared to adults.

                                                            Studying the immune response to SARS-CoV-2 in children is therefore critical to rapidly advance our understanding of the pathophysiology of COVID-19 both in children and adults. Children offer a unique possibility to study host-related factors that determine COVID-19 severity in the absence of ageing and comorbidity-related interactions, which are largely determining the disease course in adults.

                                                            We have therefore initiated a functional genetics and genomics COVID-19 study to examine the genetic and environmental risk factors of COVID-19 in pediatric and adult patients. Our group integrates deep immune profiling with multi-omics across multiple molecular levels (genome, transcriptome, proteome, metabolome) to enhance our understanding of the human immune response to SARS-CoV-2. Following questions will be addressed:

                                                            - Why does SARS-CoV-2 affect children differently compared to adults?

                                                            - What are the genetic and immunological risk factors that contribute to this difference?

                                                            - Can we use these factors to identify those children who will become severely affected?

                                                            As part of the Child Health Alliance Munich (CHANCE) initiative this prospective study is performed at the Dr. von Hauner Children’s Hospital of the Ludwig-Maximilians University (LMU) Munich and the Department of Pediatrics of the Technical University of Munich School of Medicine (TUM). The study is also actively involved in national (Deutsche COVID-19 OMICS Initiative) and international (COVID-19 Host Genetics Initiative) COVID-19 initiatives to join forces in combating this pandemic.


                                                            Dr. Sarah Kim-Hellmuth

                                                            Principal Investigator

                                                            ✉  Sarah.Kimhellmuth@med.uni-muenchen.de



                                                            Sathya Darmalinggam

                                                            Doctoral Researcher (PhD track)

                                                            ✉ Sathya.Darmalinggam@med.uni-muenchen.de


                                                            Carola Kaltenhauser

                                                            Doctoral Researcher (MD track)

                                                            ✉  Carola.Kaltenhauser@med.uni-muenchen.de


                                                            Barbara Puzek

                                                            Doctoral Researcher (PhD track)

                                                            ✉ Barbara.Puzek@helmholtz-muenchen.de


                                                            Tuguldur Tumurbaatar

                                                            Master Student

                                                            ✉ Tuguldur.Tumurbaatar@med.uni-muenchen.de



                                                            Jana Wiesel

                                                            Medical Student

                                                            ✉ Jana.Wiesel@med.uni-muenchen.de


                                                            Alina Czwienzek

                                                            Doctoral Researcher (MD track)

                                                            ✉ Alina.Czwienzek@med.uni-muenchen.de


                                                            Theresa Haslbeck

                                                            Doctoral Researcher (MD track)

                                                            ✉ Theresa.Haslbeck@med.uni-muenchen.de


                                                            Dr. Nicolás Lichilín

                                                            Postdoctoral Researcher

                                                            ✉ Nicolas.Lichilin@med.uni-muenchen.de


                                                            Lea Steinberg

                                                            Medical Student

                                                            ✉ Lea.Steinberg@med.uni-muenchen.de


                                                            Benedict Wendel

                                                            Doctoral Researcher (MD track)

                                                            ✉ Benedict.Wendel@med.uni-muenchen.de

                                                            Alumni


                                                            Anda Ardeoan

                                                            Modul 6 Student

                                                            ✉  Anda.Ardeoan@med.uni-muenchen.de



                                                            Jöran Sarrazin

                                                            Modul 6 Student

                                                            ✉ Joeran.Sarrazin@med.uni-muenchen.de


                                                            Ekin Yaman

                                                            Medical Student

                                                            ✉ Ekin.Yaman@med.uni-muenchen.de


                                                            Nishant Chintalagiri

                                                            Master Student

                                                            ✉ Chintalagiri.Nishant@campus.lmu.de


                                                            Preeti Thiyagarajan

                                                            Master Student

                                                            ✉ Preeti.Thiyagarajan@med.uni-muenchen.de


                                                            Luise Zeckey

                                                            Doctoral Researcher (PhD track)

                                                            ✉ Luise.Zeckey@med.uni-muenchen.de

                                                            Selected publications:

                                                            1. Flynn, E., Tsu, A., Kasela, S., Kim-Hellmuth, S., Aguet, F., Ardlie, K. G., Bussemaker, H. J., Mohammadi, P. & Lappalainen, T. Transcription factor regulation of eQTL activity across individuals and tissues. Plos Genet 18, e1009719 (2022).

                                                            2. Brandt, M. K., Kim-Hellmuth, S., Ziosi, M., Gokden, A., Wolman, A., Lam, N., Recinos, Y., Hornung, V. K., Schumacher, J. & Lappalainen, T. An autoimmune disease risk variant: A trans master regulatory effect mediated by IRF1 under immune stimulation? PLoS Genet 17(7), (2021). 

                                                            3. Warnat-Herresthal, S., Schultze, H., Shastry, K. L., Manamohan, S., Mukherjee, S., Garg, V., Sarveswara, R., Händler, K., Pickkers, P., Aziz, N. A., Ktena, S., Tran, F., Bitzer, M., Ossowski, S., Casadei, N., Herr, C., Petersheim, D., Behrends, U., Kern, F., Fehlmann, T., Schommers, P., Lehmann, C., Augustin, M., Rybniker, J., Altmüller, J., Mishra, N., Bernardes, J. P., Krämer, B., Bonaguro, L., Schulte-Schrepping, J., Domenico, E. D., Siever, C., Kraut, M., Desai, M., Monnet, B., Saridaki, M., Siegel, C. M., Drews, A., Nuesch-Germano, M., Theis, H., Heyckendorf, J., Schreiber, S., Kim-Hellmuth, S., […], Deutsche COVID-19 Omics Initiative (DeCOI), Giamarellos-Bourboulis, E. J., Kox, M., Becker, M., Cheran, S., Woodacre, M. S., Goh, E. L. & Schultze, J. L. Swarm Learning for decentralized and confidential clinical machine learning. Nature 1–7 (2021). 

                                                            4. de Goede, O. M., Nachun, D. C., Ferraro, N. M., Gloudemans, M. J., Rao, A. S., Smail, C., Eulalio, T. Y., Aguet, F., Ng, B., Xu, J., Barbeira, A. N., Castel, S. E., Kim-Hellmuth, S., Park, Y., Scott, A. J., Strober, B. J., GTEx Consortium, Brown, C. D., Wen, X., Hall, I. M., Battle, A., Lappalainen, T., Im, H. K., Ardlie, K. G., Mostafavi, S., Quertermous, T., Kirkegaard, K. & Montgomery, S. B. Population-scale tissue transcriptomics maps long non-coding RNAs to complex disease. Cell (2021).

                                                            5. Barbeira, A. N.*, Bonazzola, R.*, Gamazon, E. R.*, Liang, Y.*, Park, Y.*, Kim-Hellmuth, S., Wang, G., Jiang, Z., Zhou, D., Hormozdiari, F., Liu, B., Rao, A., Hamel, A. R., Pividori, M. D., Aguet, F., GTEx GWAS working group, Bastarache, L., Jordan, D. M., Verbanck, M., Do, R., GTEx Consortium, Stephens, M., Ardlie, K., McCarthy, M., Montgomery, S. B., Segre, A. V., Brown, C. D., Lappalainen, T., Wen, X. & Im, H. K. Exploiting the GTEx resources to decipher the mechanisms at GWAS loci. Genome Biol. 22, 49–24 (2021).

                                                            6. GTEx Consortium#. The GTEx Consortium atlas of genetic regulatory effects across human tissues. Science 369, 1318-1330 (2020). #Lead analyst: Kim-Hellmuth, S.

                                                               >> Science cover and Introduction to Special Issue

                                                               >> Press releases: here and here

                                                            7. Kim-Hellmuth, S.†*, Aguet, F.*, Oliva, M., Muñoz-Aguirre, M., Kasela, S., Wucher, V., Castel, S. E., Hamel, A. R., Viñuela, A., Roberts, A. L., Mangul, S., Wen, X., Wang, G., Barbeira, A. N., Garrido-Martin, D., Nadel, B., Zou, Y., Bonazzola, R., Quan, J., Brown, A., Martinez-Perez, A., Soria, J. M., GTEx Consortium, Getz, G., Dermitzakis, E., Small, K. S., Stephens, M., Xi, H. S., Im, H. K., Guigó, R., Segre, A. V., Stranger, B. E., Ardlie, K. G. & Lappalainen, T.  Cell type specific genetic regulation of gene expression across human tissues. Science 369 (2020). 

                                                               >> Featured in 'This week in Science'

                                                               >> Press releases: here and here 

                                                            8. Oliva, M.*, Muñoz-Aguirre, M.*, Kim-Hellmuth, S.*, Wucher, V., Gewirtz, A., Cotter, D., Parsana, P., Kasela, S., Balliu, B., Viñuela, A., Castel, S. E., Mohammadi, P., Aguet, F., Zou, Y., Khramtsova, E., Skol, A., Garrido-Martin, D., Reverter, F., Brown, A., Evans, P., Gamazon, E., Payne, A., Bonazzola, R., Barbeira, A. N., Hamel, A. R., Martinez-Perez, A., Soria, J. M., GTEx Consortium, Pierce, B., Stephens, M., Eskin, E., Dermitzakis, E., Segre, A. V., Im, H. K., Engelhardt, B., Ardlie, K. G., Montegomery, S., Battle, A., Lappalainen, T., Guigó, R. & Stranger, B. E. The impact of sex on gene expression and its genetic regulation across human tissues. Science 369 (2020). 

                                                               >> Science Perspective and selected media coverage: Deutschlandfunk Forschung aktuell

                                                               >> Press releases: here and here 

                                                            9. Demanelis, K., Jasmine, F., Chen, L. S., Chernoff, M., Tong, L., Delgado, D., Zhang, C., Shinkle, J., Sabarinathan, M., Lin, H., Ramirez, E., Oliva, M., Kim-Hellmuth, S., Stranger, B. E., Lai, T.-P., Aviv, A., Ardlie, K. G., Aguet, F., Ahsan, H., GTEx Consortium, Doherty, J. A., Kibriya, M. G. & Pierce, B. L. Determinants of telomere length across human tissues. Science 369 (2020). 

                                                            10. Kim-Hellmuth, S.†, Bechheim, M., Pütz, B., Mohammadi, P., Nédélec, Y., Giangreco, N., Becker, J., Kaiser, V., Fricker, N., Beier, E., Boor, P., Castel, S. E., Nöthen, M. M., Barreiro, L. B., Pickrell, J. K., Müller-Myhsok, B., Lappalainen, T., Schumacher, J. & Hornung, V. Genetic regulatory effects modified by immune activation contribute to autoimmune disease associations. Nat Commun 8, 266 (2017).

                                                            11. Kim-Hellmuth, S. & Lappalainen, T. Concerted Genetic Function in Blood Traits. Cell 167, 1167–1169 (2016).

                                                            12. Kim, S., Becker, J., Bechheim, M., Kaiser, V., Noursadeghi, M., Fricker, N., Beier, E., Klaschik, S., Boor, P., Hess, T., Hofmann, A., Holdenrieder, S., Wendland, J. R., Fröhlich, H., Hartmann, G., Nöthen, M. M., Müller-Myhsok, B., Pütz, B., Hornung, V. & Schumacher, J. Characterizing the genetic basis of innate immune response in TLR4-activated human monocytes. Nat Commun 5, 5236 (2014).

                                                            13. Kim, S., Kaiser, V., Beier, E., Bechheim, M., Guenthner-Biller, M., Ablasser, A., Berger, M., Endres, S., Hartmann, G. & Hornung, V. Self-priming determines high type I IFN production by plasmacytoid dendritic cells. Eur. J. Immunol. 44, 807–818 (2014).

                                                            14. Kim, S., Bauernfeind, F., Ablasser, A., Hartmann, G., Fitzgerald, K. A., Latz, E. & Hornung, V. Listeria monocytogenes is sensed by the NLRP3 and AIM2 inflammasome. Eur. J. Immunol. 40, 1545–1551 (2010).

                                                            15. Hornung, V., Ellegast, J., Kim, S., Brzózka, K., Jung, A., Kato, H., Poeck, H., Akira, S., Conzelmann, K.-K., Schlee, M., Endres, S. & Hartmann, G. 5'-Triphosphate RNA is the ligand for RIG-I. Science 314, 994–997 (2006).

                                                            †Corresponding author, *Equally contributing author

                                                            Complete list of publications

                                                            03/2023


                                                            Postdoc Nicolás Lichilín joins the lab


                                                            Medical student Lea Steinberg joins the lab

                                                            02/2023

                                                            Stephan Höck 


                                                            LMU INSIGHTS Article on ERC awardee Sarah Kim-Hellmuth

                                                            Read the article here

                                                            01/2023

                                                              


                                                            Master student Preeti Thiyagarajan joins the lab



                                                            Medical student Ekin Yaman joins the lab


                                                            11/2022


                                                            Sarah Kim-Hellmuth is awarded the prestigious ERC Starting grant

                                                            Read more


                                                            Master student Tuguldur Tumurbaatar joins the lab



                                                            Medical student Jana Wiesel joins the lab


                                                            09-10/2022

                                                            OSZ


                                                            Highschool lecture at OSZ Lise Meitner - School of Science

                                                            Read more



                                                            Sarah Kim-Hellmuth receives the Friedmund Neumann Prize

                                                            Read more


                                                            07-08/2022

                                                            GSK Stiftung


                                                            Sarah Kim-Hellmuth receives the GSK Foundation's Science Award

                                                            Read more (German)


                                                            Master student Nishant Chintalagiri joins the lab


                                                            05-06/2022


                                                            Panel discussion at the state occasion for the 175th birthday of the Hauner Children's hospital

                                                            YouTube video of the ceremony



                                                            Sarah Kim-Hellmuth elected as a new member of Die Junge Akademie

                                                            Read more


                                                            03-04/2022


                                                            Our group helps with organizing two concerts for children in Ukraine

                                                            Read more



                                                            MD student Theresa Haslbeck joins the lab


                                                            11/2021


                                                            PhD student Barbara Puzek joins the lab



                                                            Acceptance into the prestigious Emmy Noether programme of the DFG

                                                            Read more (German)

                                                            10/2021

                                                            Hauss/DGKJ


                                                            Sarah Kim-Hellmuth receives the Adalbert-Czerny-Award 2021

                                                            Read more (German)
                                                            Tagesspiegel Background


                                                            News article about Adalbert-Czerny Awardee Sarah Kim-Hellmuth

                                                            Read more (German)

                                                            09/2021


                                                            PhD student Luise Zeckey joins the lab

                                                            05-06/2021

                                                            Nature


                                                            Our study contributes to a novel swarm learning approach to identify COVID patients

                                                            Read more


                                                            KIT2021


                                                            Carola Kaltenhauser presents her poster at KIT 2021

                                                            Find the abstract here


                                                            04/2021


                                                            Our 1st Ped-COVID-19 virtual Symposium

                                                            Find the agenda here



                                                            Official start of the Helmholtz Young Investigator Group "Immunogenomics"



                                                            03/2021

                                                            VIB Conferences


                                                            Invited talk at VIB Conference: Revolutionizing Next-Generation Sequencing

                                                            Learn more


                                                            11-12/2020


                                                            Our COVID-19 case report in a pediatric patient with Down syndrome is out in JPIDS

                                                            Read more



                                                            MD student Alina Czwienzek joins the lab



                                                            10/2020


                                                            PhD student Sathya Darmalinggam joins the lab



                                                            MD student Jöran Sarazzin joins the lab


                                                            09/2020


                                                            Radio report on the GTEx project with Sarah Kim-Hellmuth

                                                            Listen



                                                            Our GTEx Cell Type Group Paper is out in Science

                                                            Read more



                                                            MD student Ben Wendel joins the lab



                                                            The GTEx Main Paper is out in Science

                                                            Read more

                                                            See also the complete list of all GTEx papers



                                                            Our GTEx Sex Group Paper is out in Science

                                                            Read more


                                                            08/2020


                                                            MD student Anda Ardeoan joins the lab


                                                            06/2020


                                                            Sarah Kim-Hellmuth presents her work at ESHG 2020 

                                                            Find out more


                                                            04/2020


                                                            MD Student Carola Kaltenhauser joins the lab 



                                                            News article covering our Ped-COVID-19 study  

                                                            Find out more



                                                            Ped-COVID-19 study joins the German COVID-19 OMICS Initiative  

                                                            Find out more


                                                            03/2020


                                                            The Ped-COVID-19 study is launched 



                                                            Ped-COVID-19 study joins the international COVID-19 Host Genetics Initiative  

                                                            Find out more


                                                            Welcome lunch with our new members Jana and Tuulu  

                                                            Our group at the Hauner concert for children in Ukraine

                                                            Welcome lunch with our new PhD student Luise

                                                             Lab outing Summer 2022                                

                                                            First CompHealth retreat at HMGU

                                                            Welcome lunch with our new MD student Theresa 

                                                            Sathya and Barbara at CGSI 2022

                                                            Lab picture after our first Ped-COVID-19 symposium

                                                            First lab outing after a long lockdown

                                                            Open positions: 

                                                            • Bioinformatician in Human Genomics and Immunology
                                                            • Working student

                                                            We are actively looking to expand our group at all levels (postdocs, senior and junior staff scientists, graduate students, interns). Given our interdisciplinary work we offer both dry and wet lab projects and are looking for highly motivated individuals with diverse scientific backgrounds (immunologists, clinicians, computational biologists, statistical geneticists, data scientists).

                                                            • Fascinated by the immune system and its complexity and diversity among us human beings?
                                                            • Driven to better understand genetic gene regulation and its role in immune-related diseases?
                                                            • Interested in applying cutting-edge genomics technologies and analytical approaches to answer some of the pressing questions in genetics & genomics and immunology?
                                                            • Enjoy working in an interdisciplinary and collaborative team surrounded by a vibrant scientific environment?


                                                            Then look no more!

                                                            Our group is dedicated to better understand the genetic basis of human immune response variation and translate those insights into the clinic to improve every day medical decision-making. Located both at Helmholtz Munich and the LMU University hospital we are embedded and collaborate in a wide scientific network, in particular with the Computational Health Center, the Department of Pediatrics, the Biomedical Center, the Gene Center Munich and of course nationally and internationally. 

                                                            If you are interested in discussing projects or job opportunities please get in touch via email. This can be even very early before your potential start or before major conferences to meet informally.

                                                            Diversity and inclusivity are key values in our group. We welcome applicants from all backgrounds especially from underrepresented and underprivileged backgrounds. 

                                                            Kim-Hellmuth Lab

                                                            Dr. von Hauner Children's Hospital, University Hospital LMU Munich

                                                            Lindwurmstraße 4
                                                            80337 Munich
                                                            +49-89-4400-519821 +49-89-4400-57418 E-Mail

                                                            Research at CCRC Hauner

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                                                            Kinderklinik und Kinderpoliklinik

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