Project Description

Cellular effects of loss-of-function mutations in DNAH9. Image taken from Loges et al., (2018), Am J Hum Genet.

Miriam Schmidts, MD

ERC group leader, Clinical Fellow
E: miriam.schmidts@uniklinik-freiburg.de
T: +49 (0)761 270 43000

Pediatric Research Laboratory
Elssässerstraße. 2q
79110 Freiburg
Germany

Our main research focus is on elucidating the molecular mechanisms of rare inherited conditions using gene discovery as well as in vitro and in vivo gene editing approaches. We have a longstanding expertise in motile and non-motile ciliopathies and more recently also include non-ciliary renal diseases as well neurodevelopmental conditions.

TEAM

Motile ciliopathies/Laterality defects

Dinu Antony (PhD student)
Ilona Skatulla (RA)

Non-motile ciliopathies

Dr. Zeineb Bakey (PhD)
Dinu Antony (PhD student)
Dr. Isabel Schüle (MD)
Ilona Skatulla (RA)

Molecular mechanism of rare renal diseases

Dr Isabel Schüle (MD)
Dr. Maryam Najafi (PhD)
Minh Nguyen (PhD, Radboudumc Nijmegen)
Ilona Skatulla (RA)

Rare Disease genetics, neurodevelopmental diseases

Dr. Maryam Najafi (PhD)
Abolfazl Rad

RESEARCH THEMES

Major topics of the laboratory are

  • Ciliopathies/Laterality defects: We employ state-of-the art next generation sequencing technologies to identify novel disease-causing genes in humans and dissect genotype-phenotype correlations. Further, we generate both Null- as well as hypomorphic loss-of-function models using renal cell lines, chondrocyte precursor cells and zebrafish systems to scrutinize downstream cell signaling networks employing transcriptomics and cilia-specific proteomics approaches. In addition, we utilize small compound screening to identify therapeutic substances for skeleto-renal ciliopathies.
  • Rare Disease genetics: Rare diseases together are a frequent cause of chronic illness, disability and reduced life span and often, the underlying genetic defect is unclear, hampering precise personalized clinical care. Exome and genome sequencing has evolved as a cost- and time-efficient tool to elucidate the underlying genetic basis for rare diseases. Our main emphasis lies on ciliopathies, inherited renal diseases and neurodevelopmental syndromes, where we aim to identify novel disease-causing genes and work on genotype-phenotype correlations.
  • Molecular mechanism of rare renal diseases: Childhood-onset renal failure is often caused by genetic conditions; however precise mechanisms are poorly understood and no curative treatment is available to date. We employ gene discovery approaches as well as functional in-depth investigation of renal development in vitro and in vivo.

FUNDING

COLLABORATIONS, CO-OPERATIONS, AND NETWORKS

SELECTED RECENT PUBLICATIONS

ORCID https://orcid.org/0000-0002-1714-6749

  • Schmidts M*, Hou Y*, Cortes CR, Mans DA, Huber C, …,Witman GB. TCTEX1D2 mutations underlie Jeune asphyxiating thoracic dystrophy with impaired retrograde intraflagellar transport. Nat Commun 6, 7074 (2015). https://doi.org/10.1038/ncomms8074
  • Wheway G*, Schmidts M*, Mans DA*, Szymanska K*, Nguyen TT*, …, Johnson CA. An siRNA-based functional genomics screen for the identification of regulators of ciliogenesis and ciliopathy genes. Nat Cell Biol 17, 1074-1087 (2015). https://doi.org/10.1038/ncb3201

Complete list of publications: https://www.ncbi.nlm.nih.gov/pubmed/?term=schmidts+m