Pediatric Antiviral Immunity and Innate Inflammatory Signaling

Pediatric Antiviral Immunity and Innate Inflammatory Signaling2024-11-14T13:44:41+01:00

Roland Elling, PD, Dr. med.

Head of Division for Pediatric Infectious Disease Research and Epidemiology

E: roland.elling@uniklinik-freiburg.de
E: zkj.pif@uniklinik-freiburg.de

Medical Center – University of Freiburg
Center for Pediatrics and Adolescent Medicine
Breisacher Str. 62
79106 Freiburg, Germany

The Pediatric Infectious Disease Research Freiburg (PIF) group focuses on the molecular pathogenesis, immune response, and improved diagnostics of viral infections in children, combining clinical studies with basic research.

Additionally, this group is interested in monogenetic immunodeficiencies of the innate immune system.

IL1β Inhibition in NLRP12 Mutations

NLRP12 has been shown to play an important role in the formation of inflammasomes and the regulation of T cells as well as a negative regulator of NFkB and MAPK signaling pathways.

In patients with NLRP12 mutations, we are focused on better understanding the role of NLRP12 in innate immunity and the molecular consequences of dysregulation of the affected signaling pathways. Furthermore, we are interested in investigating the effect of IL1β inhibition in NLRP12 mutations to provide effective and feasible long-term treatment options for patients.

Exploring Pathological Neutropenia in Cohen Syndrome
Neutrophil granulocytes play an important role in the early immune response against invading pathogens. Rare genetic mutations in the VPS13B gene affect neutrophil biology in patients suffering from Cohen syndrome, leading to increased susceptibility to mild infections. Our goal is to investigate the underlying mild to severe neutropenia of unknown pathophysiology using primary biomaterial from affected pediatric patients.

Parechovirus Infections in Neonates and Young Infants

Human parechoviruses (HPeV) are emerging pathogens within the Picornaviridae family and frequently cause gastrointestinal and respiratory illness in children. Most HPeV infections manifest asymptomatic or with mild symptoms, including fever, upper respiratory tract symptoms, gastroenteritis, and rash. Severe disease, however, such as meningoencephalitis, seizures or sepsis-like illness are almost exclusively associated with HPeV-3 infections in infants <3 months. Despite high global prevalence and clinical relevance, little research has been done on the pathogenesis of human parechoviruses. Our focus is to investigate the genotype-specific disease association and HPeV interactions with the immune system.

Sex-Specific Immune Responses in Severe Echovirus 11 Infections Among Neonates

Echovirus 11 (E11) is a central viral cause of sepsis, fulminant hepatitis and other severe systemic disorders in young infants. Notably, severe E11 cases predominantly affect male infants, suggesting possible sex-specific differences in immune response. However, the pathogenesis of E11, including the involved innate immune signaling axes as well as the sex bias in severe cases towards males, remains poorly understood. Our goal is to identify possible sex-dependent, as well as age-dependent mechanisms mediating protection or susceptibility against severe E11 infections.

Postviral Illness in Pediatric Patients – Focus 

Pediatric patients may experience new or lingering symptoms following viral infections. When these symptoms persist for more than three months after a SARS-CoV-2 infection, the condition is referred to as Post-COVID Syndrome. Children and adolescents with this syndrome can exhibit ongoing symptoms like chronic fatigue, post-exertional malaise, and brain fog. Underlying pathophysiology remains unclear. PIF leads the biomarker part of “Molecular immunological characterization & multimodal-multicentric care of Long COVID in children and adolescents in Baden-Württemberg” (https://move-covid.de/). This translational study collects neuropsychological and clinical data as well as multiple biomaterials longitudinally from severely affected pediatric patients suffering from Chronic Fatigue Syndrome focusing on Post-COVID-Syndrome on four different study sites. Our goal is to investigate the underlying pathophysiology via metabolomics, whole genome sequencing and advanced immunological and radiological approaches.

Evaluating the need of lumbar punctures in young, well-looking febrile infants and the risk of severe bacterial central nervous system infections

This study evaluates the need for cerebral spinal fluid analysis in the well-looking, febrile infant being 0 to 6 months of age. All patients in the emergency department of the University Hospital of Freiburg from 2009 to 2024 who met the criteria were included. Key question is whether lumbar punctures should remain a part of the routine work-up of a febrile young infant or whether less invasive diagnostics can detect the risk of severe bacterial infection reliably. This retrospective study correlates microbiological pathogen detection in cerebral spinal fluid to numerous clinical and laboratory-chemical parameters as well as further microbiological and virological diagnostics.

REMUS – Rapid Risk Stratification of Acute RSV Infection in Infants

Acute viral respiratory infections are a leading cause of hospital visits among infants, with Respiratory Syncytial Virus (RSV) being the most prevalent. Differentiating RSV disease phases and predicting the severity at the patient’s initial presentation remains challenging. This project, in collaboration with industry and academic partners, aims to develop a rapid point-of-care test for RSV (REMUS) that combines viral and host-specific biomarkers to enhance diagnostic precision. Key research questions include whether the combined analysis of pathogen- and host-specific infection markers can accurately indicate infection phase and predict disease progression, providing a reliable tool for risk stratification in clinical settings.

TEAM

If you are interested in joining our research team as an MD or PhD student or as a postdoc, please contact Roland Elling (roland.elling@uniklinik-freiburg.de)
with a short description of your research experience and interests.

Group Leader: PD. Dr. Roland Elling

Team members:

  • Alexander Hilger (PhD candidate)
  • Anna Willems (postdoc)
  • Tessa Görne (postdoc)
  • Bianca Rippberger (study coordinator)
  • Pauline Frieh (MD student)
  • Svea Böhm (postdoc)
  • Alexandra Müller-Hagemann (postdoc)
  • Lena Schuler (MD)
  • Bhoomika Subramani (master student)
  • Miriam Eisner (MD student)
  • Cornelis Escher (MD student)
  • Jonathan Senst (MD student)

Former Members:

  • Bärbel Maag

PD Dr. Roland Elling
Head, Division of Pediatric infectious disease Research and Epidemiology
Attending Physician, Board-certified Pediatrician and Infectious Disease Specialist

E: roland.elling@uniklinik-freiburg.de
T: +49 (0) 761 270 – 43000

Education, training, career

  • Since: 2024 Head, Division of Pediatric infectious disease Research
  • 2023: Senior lectureship („Habilitation”)
  • Since 2023: Attending physician, University Medical Center Freiburg Center of Pediatrics
  • 2020: Junior group leader, pediatric antiviral immunity
  • 2014-2016: Postdoctoral training in Katherine Fitzgerald’s lab in Worcester/MA, USA
  • Training in Pediatrics and Infectious Diseases in Freiburg
  • Medical Studies in Würzburg, Kathmandu and Basel

Grants and awards

  • 2022-2024: Berta Ottenstein program for Advanced Clinician Scientists, University of Freiburg
  • 2018: Award for outstanding teaching, Medical faculty Freiburg
  • 2016: Theodor Escherich Award, German Society for Pediatric Infectious Diseases
  • 2016-2019: Berta Ottenstein Clinician Scientist program, University of Freiburg
  • 2014-2016: Research fellowship, German Research foundation (DFG)
  • German Academic Scholarship Foundation (Studienstiftung des deutschen Volkes)

Key research areas

  • Antiviral immunity and innate inflammatory signaling in children
  • Improved diagnostics of viral and bacterial infections in children

Key methods

  • CRISPR
  • Cloning

ORCID-Link/ PubMed Link

For a complete publication list, please see here:

ORCID: 0000-0002-2209-4154

PubMed: pubmed.ncbi.nlm.nih.gov

LIST OF FUNDING SOURCES

  • Gilead Research Grant
  • MWK Baden-Württemberg
  • Sozialministerium Baden-Württemberg
  • BMG
  • DFG
  • Berta-Ottenstein Clinician Scientist Program

SELECTED RECENT PUBLICATIONS

For a complete publication list for Roland Elling, please use the following links:

PubMed: www.ncbi.nlm.nih.gov/pubmed
ORCID: 0000-0001-5986-0468

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