Nußbaum Lab
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Research topics
- Human perinatal immune cell development
- Biomarker Research in neonatal sepsis
- Birth Cohort of Preterm and Term neonates (MUNICH PreTCL)
- Microcirculation and Glycocalyx alteration in development and disease
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Current projects:
MUNICH PreTCL CohortTo better understand the physiological and pathological processes that determine the individual phenotypes of neonates, we have established the Munich Preterm and Term Clinical (MUNICH-PreTCl) birth cohort (#Pangratz-Fuehrer et al., 2021) that econmpises > 800 neonates (~550 term and ~ 260 preterm) and is currently still recruting.
We collect dried blood spot samples from term infants at the time of the newborn screening and during suspected or proven infection and from preterm infants longitudinally including up to 4 time points (after birth, at newborn screening, at adjusted 32 weeks of gestation and at discharge) to generate MS-based blood proteomes in collaboration with the group of Prof. Mann at the Max Planck Institute of Biochemistry. To enable later adjustment for possible influence factors, we gather extensive clinical data (e.g. birth-related data, treatments, complications) and laboratory data of infants as well as information on parental demographics and anthropometric data, family history, pregnancy (e.g prenatal screenings, infections and substance abuse) and birth resulting in 450 data points per child-parent set.
Genetic regulation of protein expression during immune cell development in human neonatesThe project is part of the DFG-funded transregio TRR 359 PILOT
Find out more under www.perinatal-immunity.de/en
The 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). To date, the genetic basis of human perinatal immune cell variability is still poorly understood and largely understudied.
In this collaborative resarch project together with Dr. Sarah Kim-Hellmuth‘s lab and the pedatric proteomic unit (Dr. Susanne Pangratz-Führer, Dr. Johannes Müller-Reif) we will establish multi-omic profiling in neonatal dried-blood spot (DBS) samples to uncover the genetic effect on protein expression and its cell type-specificity in neonatal proteomes from 662 newborns of a wide range of gestational ages.
Extracellular Vesicle Analysis in Neonatal Early Onset Sepsis (EVANEOS Study)Infections in newborns remain a leading cause of neonatal mortality and lifelong disability. Each year, severe bacterial infections kill approximately 400,000 newborns worldwide. Early diagnosis and treatment are crucial but challenging, particularly for early onset sepsis (EOS), due to the nonspecific initial symptoms and limited early-stage diagnostic tools.
This project aims to improve the diagnosis of EOS, which currently results in many neonates being unnecessarily separated from their mothers and subjected to invasive diagnostics and treatments. We will study a cohort of term newborns exposed to specific EOS risk factors (prolonged rupture of membranes, group B streptococci in the mother, and clinical signs of chorioamnionitis) but without other complications or comorbidities during pregnancy.
Our analyses will include:
a) Isolation and characterization of extracellular vesicles from the umbilical cord blood of at-risk neonates and maternal blood (collaboration PD Dr. Reithmair, LMU and Prof.. Michael Pfaffl, TUM School of Life Sciences.
b) Identification of microbiome signatures and potential infection routes in suspected EOS cases by characterizing the gut microbiome through shotgun sequencing and performing 16S rRNA gene amplicon sequencing of blood samples (collaboration Prof. Thomas Clavel, University of Aachen)
Functional and structural investigation of the microcirculation in SARS-CoV2 related diseasesThe vascular endothelium is crucial in SARS-CoV-2 pathogenesis. The virus targets cells via ACE2 receptors, degrades the protective glycocalyx, and causes persistent endothelial dysfunction in Long-COVID patients. Despite milder initial illness, children suffer from SARS-CoV2 related diseases including long-COVID and mutisystem inflammatory syndrom in children (MIS-C), a severe pediatric complication.
In collaboration with the the team of Andre Jacob (pediatric cardiology, LMU) we investigate microcirculatory changes and molecular signatures of SARS-CoV-2 related diseases in children. Using a longitudinal design, microcirculation parameters will be assessed in children/adolescents with acute COVID-19, PIMS, Long COVID, and asymptomatic SARS-CoV-2 infection during the acute phase and three months post-recovery.
Clinical neonatal studies
Impact of Perinatal Asphyxia on Child Development and Parental Stress (ImPACS)This project aims to analyze the developmental neurological outcomes of patients aged 1-6 years following perinatal asphyxia of varying severity, and the impact on parents, including any long-term effects. So far, 179 control subjects and 135 patients with perinatal asphyxia have been included in the study. The results are expected to provide insights into the extended indications for hypothermia treatment and identify factors that positively and negatively influence parental stress, helping to prevent post-traumatic stress disorders.
Investigation of Pathogen Transmission in Two Neonatal Intensive Care Units: Impact of Spatial Changes and Effectiveness of Targeted Hygiene InterventionsThe goal of this project is to evaluate whether relocating the neonatal intensive care unit and the associated spatial changes have led to a reduction in pathogen transmission between patients. Additionally, the project aims to assess the benefits of targeted staff training on adherence to and improvement of hygiene measures.
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Alumni
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Selected Publications
Association between inflammation, glycocalyx biomarkers, and endothelial function in children with hypercholesterolemia. Pastor-Villaescusa B, Meier J, Ruske F, Prell C, Gruezner J, Koenig M, Jakob A, Koletzko B, Nussbaum C. Ann Nutr Metab. 2024 Feb 5. doi: 10.1159/000536042. Online ahead of print. PMID: 38316115
Long-Term Microvascular Changes in Multisystem Inflammatory Syndrome in Children. Boever J*, Nussbaum C*, Arnold L, Haas NA, Dold SK, Oberhoffer FS, Jakob A. JAMA Pediatr. 2024 Mar 1;178(3):304-306. doi: 10.1001/jamapediatrics.2023.6022. PMID: 38227331 * equal contrib.
Cyclophilin A is a ligand for RAGE in thrombo-inflammation. Seizer P, von Ungern-Sternberg SNI, Haug V, Dicenta V, Rosa A, Butt E, Nöthel M, Rohlfing AK, Sigle M, Nawroth PP, Nussbaum C, Sperandio M, Kusch C, Meub M, Sauer M, Münzer P, Bieber K, Stanger A, Mack AF, Huber R, Brand K, Lehners M, Feil R, Poso A, Krutzke K, Schäffer TE, Nieswandt B, Borst O, May AE, Zernecke A, Gawaz M, Heinzmann D. Cardiovasc Res. 2024 Mar 30;120(4):385-402. doi: 10.1093/cvr/cvad189. PMID: 38175781.
A20 and the noncanonical NF-κB pathway are key regulators of neutrophil recruitment during fetal ontogeny. Rohwedder I, Wackerbarth LM, Heinig K, Ballweg A, Altstätter J, Ripphahn M, Nussbaum C, Salvermoser M, Bierschenk S, Straub T, Gunzer M, Schmidt-Supprian M, Kolben T, Schulz C, Ma A, Walzog B, Heinig M, Sperandio M. JCI Insight. 2023 Feb 22;8(4):e155968. doi: 10.1172/jci.insight.155968. PMID: 36633909.
Kawasaki disease and increased cardiovascular risk: Is there a link to circulating glycocalyx biomarkers?. Jakob A, Bohlig S, König M, Nussbaum C, Dalla-Pozza R, Hermann M, Haas NA, Pastor-Villaescusa B. Microvasc Res. 2022 Mar;140:104269. doi: 10.1016/j.mvr.2021.104269. Epub 2021 Oct 23. PMID: 34699846
Cohort profile: the MUNICH Preterm and Term Clinical study (MUNICH-PreTCl), a neonatal birth cohort with focus on prenatal and postnatal determinants of infant and childhood morbidity. Pangratz-Fuehrer S, Genzel-Boroviczény O, Bodensohn WE, Eisenburger R, Scharpenack J, Geyer PE, Müller-Reif JB, van Hagen N, Müller AM, Jensen MK, Klein C, Mann M, Nussbaum C. BMJ Open. 2021 Jun 24;11(6):e050652. doi: 10.1136/bmjopen-2021-050652. PMID: 34168035
Effect of gestational age and postnatal age on the endothelial glycocalyx in neonates. Puchwein-Schwepcke A, Artmann S, Rajwich L, Genzel-Boroviczény O, Nussbaum C. Sci Rep. 2021 Feb 4;11(1):3133. doi: 10.1038/s41598-021-81847-8. PMID: 33542284
Maturation of Platelet Function During Murine Fetal Development In Vivo. Margraf A*, Nussbaum C*, Rohwedder I, Klapproth S, Kurz ARM, Florian A, Wiebking V, Pircher J, Pruenster M, Immler R, Dietzel S, Kremer L, Kiefer F, Moser M, Flemmer AW, Quackenbush E, von Andrian UH, Sperandio M. Arterioscler Thromb Vasc Biol. 2017 Jun;37(6):1076-1086. doi: 10.1161/ATVBAHA.116.308464. Epub 2017 Apr 20. PMID: 28428216
Sphingosine-1-phosphate receptor 3 promotes leukocyte rolling by mobilizing endothelial P-selectin. Nussbaum C, Bannenberg S, Keul P, Gräler MH, Gonçalves-de-Albuquerque CF, Korhonen H, von Wnuck Lipinski K, Heusch G, de Castro Faria Neto HC, Rohwedder I, Göthert JR, Prasad VP, Haufe G, Lange-Sperandio B, Offermanns S, Sperandio M, Levkau B. Nat Commun. 2015 Apr 2;6:6416. doi: 10.1038/ncomms7416. PMID: 25832730
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Nußbaum Lab
Dr. von Hauner Children's Hospital, University Hospital LMU Munich
Lindwurmstraße 4+49-89-4400-32220 +49-89-4400-32241
80337 MunichyägfmlgJ-u:fccjJgfvSvimsful_vfiuyziusmi