Metabolism and Cofactor Enzymology2021-04-09T10:23:18+02:00

Project Description

Luciana Hannibal, PhD

Research Group Leader
Head of the Metabolomics Core Facility
Project Leader and Scientific Board Member of EHOD

E: luciana.hannibal@uniklinik-freiburg.de
T: +49 (0)761 270 43710

Medical Center– University of Freiburg
Department of Pediatrics
Department of General Pediatrics, Adolescent Medicine and Neonatology
Elsässerstr. 2Q
79110 Freiburg
Germany

Our research investigates rare diseases of B-vitamin metabolism with a strong focus on genetic determinants of vitamin B12 deficiency (Figure 1). Vitamins of the B-group, namely pyridoxal phosphate (B6), folate (B9) and cobalamin (B12) are essential for the methionine cycle, one-carbon metabolism and transsulfuration reactions. We investigate how mutations in proteins and enzymes disrupt activity, cofactor binding, redox signaling, and protein-protein interactions (Figure 2), and their impact on disease onset, progression and phenotype heterogeneity. Using a combination of biophysical, omics, mass spectrometry, site-directed mutagenesis, and cell culture methodologies we seek to elucidate the molecular determinants of phenotype heterogeneity in genetic diseases of metabolism.

Figure 1: Cellular roadmap of cobalamin utilization and genetic determinants of inborn errors of metabolism (cblA-cblX, and mut). From Hannibal et al. 2016.

Figure 2: Structure of human MMACHC with bound cobalamin. Glutathione binding residues are shown in purple. From Hannibal, L and Jacobsen, DW, 2017.

Our methodological approach:

  • Metabolic labeling in cell culture
  • Targeted metabolic profiling by liquid chromatography and mass spectrometry
  • Genetic engineering of proteins and in silico function prediction
  • Recombinant protein expression and high-scale purification
  • Rapid kinetics enzymology by stopped-flow
  • Clinical Metabolomics

Our major research questions are:

1) Do protein and metabolite changes drive clinical manifestations in inborn errors of metabolism?

2) Do these pathology-specific features change during lifetime; i.e. as children become adolescents and adults?

3) Could we target these metabolic features (proteins, enzymes, metabolites) and correct the metabolic defect via repurposing of existing drugs or the development of new therapies?

TEAM

Our group approaches scientific questions using a variety of methodologies that require multidisciplinary expertise. Students and professionals in the fields of chemistry, pharmacy, biology and medicine are welcome to submit applications for undergraduate and graduate studies and research fellowships in translational research.

BASIC RESEARCH

Enzymology and repair of pathogenic variants of the human MMACHC protein of combined homocystinuria and methylmalonic aciduria

  • Anna Esser (MD student)
  • Srijan Mukherjee (Master Student)
  • Katharina Klotz (Technical Assistant)

Bioactivity and testing of new cobalamin derivatives for the treatment of inborn errors of metabolism

  • Srijan Mukherjee (Master Student)

Targeted metabolomics analysis of inborn errors of metabolism that lead to energy deficiency

  • Nahuel R. Marziali (MD student)
  • Alexandra Altmann (MD student)
  • Julia Durif (MD student)
  • Katharina Klotz (Technician in training)

Biosynthesis and detection of hydrogen sulfide in cystathionine beta synthase deficiency, classic homocystinuria

  • Joanna Myszkowzka (MD student)

Natural and engineered variants of cytochrome c: conformational and functional analysis

  • Florencia Tomasina (PhD student, collaboration with Prof. Dr. Rafael Radi)

CLINICAL RESEARCH

Clinical research projects are carried out in collaboration with PD. Dr. Sarah Grünert.

Elevated plasma vitamin B12 in inborn errors of metabolism

  • Alexandra Altmann (MD student)
  • Julia Durif (MD student)
  • Julia Hinkel (MD student)

Metabolomic biomarkers of vascular health in patients with glycogen storage diseases

  • Johannes Schmitt (MD student)
  • Jule Theimer (MD student)
  • Katharina Klotz (Technician in training)

ALUMNI

  • Melissa Klenzendorf, RA (currently at CIBSS, University of Freiburg, Germany)
  • Valerie Chaumet, MSc (currently pursuing PhD studies, Saarland University, Germany)
  • Carla Ojeda, MSc (IMBS graduate, currently in Ecuador)
  • Segun Tanimowo, Dr. med. (IMBS graduate, currently practicing medicine, UK)
  • Victoria Wingert, MSc. (currently in industry, Germany)
  • Sidney Behringer, MSc. (currently in industry, Switzerland)
  • Suelen Basgalupp, PhD. (currently pursuing postdoctoral research, Brazil)

SELECTED RECENT PUBLICATIONS

For a complete publication list for Luciana Hannibal, please use the following links:

PubMed:https://www.ncbi.nlm.nih.gov/pubmed/?term=Luciana+Hannibal

ORCID: https://orcid.org/0000-0002-0911-5758

Scopus: https://www2.scopus.com/authid/detail.uri?authorId=16306673300

PATENTS AND INVENTION DISCLOSURES

International Patent Application Nr. PCT/EP2018/063597, Publication Nr. WO/2018/215578. Cobalamin derivatives and their use for the treatment of diseases caused by lack of vitamin B12 supply. Filing year: 2017

Invention Disclosure ZEE20170213. A capture method for the accurate and real-time detection of hydrogen sulfide (H2S) in biological samples. Filing year: 2017

COLLABORATIONS, CO-OPERATIONS AND NETWORKS

Networks and Cooperations

Collaboration Partners:

FUNDING

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