Kim-Hellmuth Lab
Emmy Noether Research Group
-
Research topics
- Genetic influence on human immune response variation
- Genetic ancestry effects on the human immune system
- Human perinatal immune cell development
- Molecular characterization of COVID-19 infections in children and young adults
Dr. med. Sarah Kim-Hellmuth
✉ Sarah.Kimhellmuth@med.uni-muenchen.de
🐦/X: @skimhellmuth
Profile at Die Junge Akademie: Click here
Profile at #InnovativeFrauen: Click here
-
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.
Genetic regulation of protein expression during immune cell development in human neonatesThe composition and maturity of immune cells exhibits high interindividual variability in preterm and term human newborns. Quantitative and qualitative changes of neonatal neutrophils are thought to contribute to the increased susceptibility to bacterial infections and neonatal sepsis that are still a leading causes of mortality and long-lasting morbidity. This interindividual variability is shaped by genetically hard-wired programs, the rapidly changing environment, and the interaction between those two (GxE interaction). While elaborate perinatal models in mice and other model systems enable comprehensive research on environmental factors that influence perinatal immune cell development, the genetic basis of human perinatal immune cell variability is still poorly understood and largely understudied.
In this project we investigate the role of cis-regulatory variants on protein expression during perinatal immune cell development in human neonates. To do this, we use the Munich Preterm and Term clinical (MUNICH-PreTCl) birth cohort. Integrating proteome profiles and genotype information of each participant, we will identify genetic variants that determine the variability in protein abundance in neonatal blood samples at defined gestational time points. These so-called protein quantitative trait loci (pQTL) offer insight into how genetics shape individual phenotypes by understanding the subsequent modulation of distinct protein expression profiles.
COVID-19 in children and young adultsCOVID-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.
-
Alumni
-
Selected publications:
1. Nussbaum, C. & Kim-Hellmuth, S. Unlocking the genetic influence on milk variation and its potential implication for infant health. Cell Genom. 4, 100676 (2024).
2. Kasela, S., Aguet, F., Kim-Hellmuth, S., Brown, B. C., Nachun, D. C., Tracy, R. P., Durda, P., Liu, Y., Taylor, K. D., Johnson, W. C., Berg, D. V. D., Gabriel, S., Gupta, N., Smith, J. D., Blackwell, T. W., Rotter, J. I., Ardlie, K. G., Manichaikul, A., Rich, S. E., Barr, R. G. & Lappalainen, T. Interaction molecular QTL mapping discovers cellular and environmental modifiers of genetic regulatory effects. Am J Hum Genet 111(1) (2024).
3. 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).
4. 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).
5. 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).
6. 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).
7. 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).
8. 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
9. 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
10. 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
11. 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).
12. 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).
13. Kim-Hellmuth, S. & Lappalainen, T. Concerted Genetic Function in Blood Traits. Cell 167, 1167–1169 (2016).
14. 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).
15. 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).
16. 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).
17. 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
-
09/2024
Senior Bioinformatician Susanne Horn, PhD joins the lab
PhD student Furkan Büyükgöl joins the lab
07/2024
Clinician scientist Dr. med. Paula Rothämel joins the lab
04/2024
Staff scientist Juliane Klein joins the lab
Clinician scientist Dr. med. Jessica Jin joins the lab
03/2024
Official start of our ImmGenDC Uganda team in Kyamulibwa
Master student Franziska Schweiger joins the lab
Master student Deniz Eser joins the lab
Medical student Sophia Grotz joins the lab
01/2024
Kick-off meeting of our ERC Starting Grant project ImmGenDC with our collaborators at MRC Uganda
Postdoc Marie Bourdon, PhD joins the lab
MD student Aleksandra Jucha joins the lab
12/2023
Medical student Mara Franzl joins the lab
11/2023
10/2023
Panel discussion at the Retreat of the LMU Medical & Clinician Scientist Program (MCSP)
PhD student Alessandro Mattia joins the lab
09/2023
Sathya Darmalinggam's poster presentation at the first joint conference of the French and German Societies of Immunology
Tuguldur Tumurbaatar's poster presentation at the first joint conference of the French and German Societies of Immunology
06/2023
Medical student Laura Jänisch joins the lab
05/2023
Sarah Kim-Hellmuth is portrayed in the children’s book “Young Scientists” of Die Junge Akademie
04/2023
MD student Mirjam Schobel joins the lab
Master student Pauline Kuschel joins the lab
03/2023
Bioinformatician Nicolás Lichilín, PhD joins the lab
Medical student Lea Steinberg joins the lab
02/2023
Research fellow Dr. med. Tobias Franz joins the lab
01/2023
Master student Preeti Thiyagarajan joins the lab
Medical student Ekin Yaman joins the lab
202211/2022
Master student Tuguldur Tumurbaatar joins the lab
Medical student Jana Wiesel joins the lab
09-10/2022
07-08/2022
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
03-04/2022
MD student Theresa Haslbeck joins the lab
202111/2021
PhD student Barbara Puzek joins the lab
10/2021
09/2021
PhD student Luise Zeckey joins the lab
05-06/2021
04/2021
Official start of the Helmholtz Young Investigator Group "Immunogenomics"
03/2021
202011-12/2020
MD student Alina Czwienzek joins the lab
10/2020
PhD student Sathya Darmalinggam joins the lab
Medical student Jöran Sarazzin joins the lab
09/2020
08/2020
Medical student Anda Ardeoan joins the lab
06/2020
04/2020
MD student Carola Kaltenhauser joins the lab
03/2020
The Ped-COVID-19 study is launched
-
ImmGenDC Uganda team meeting
Cake day after ESHG 2024
Our group at the SFI-DGfI joint conference 2023
ITG Retreat 2023 at Starnberger See
Sathya and Barbara at CGSI 2022
Lab after our first Ped-COVID-19 symposium
First lab outing after a long lockdown
Attending the CSAMA summer school in Brixen, Italy
Our group at ESHG 2024
Visit to Oide Wiesn
Welcome lunch with our new members Jana & Tuulu
Our group at the Hauner concert for children in Ukraine
Welcome lunch with our new PhD student Luise
Poster presentation at the CoPILOT retreat
Marie and Jessica at the Wellcome Genome Campus
Lab outing Summer 2023
Lab outing Summer 2022
First CompHealth retreat at HMGU
Welcome lunch with our new MD student Theresa
-
Open positions:
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+49-89-4400-519821 +49-89-4400-57418
80337 MunichRgpgz Ülvziäävfbzvimeful+vfiuyziu mi