Dr Thierry Nouspikel

MD, PhD, FAMH Medical Genetics
 


 


 


 


 


 

Innovation Scientific Manager FAMH, Genesupport, Switzerland

President-FAMH, Swiss Society for Medical Genetics (SGMG/SSGM)

Federal Advisory Commission for Genetic Testing in Humans (GUMEK/CFAGH)

Commission of lab directors, Swiss Academy of Medical Sciences (SAMW/ASSM)

 

Education:

1980 College Claparede, Geneva, Switzerland.  Baccalaureate (valedictorian).
1987 University of Geneva, School of Medicine. Diploma in medicine.
1992 University of Geneva, School of Medicine.  MD degree.
1996 University of Geneva, School of Sciences.  PhD in biology
 

Previous positions and Employment:

1988-1992 MD student, Dept of Clinical Biochemistry, University of Geneva. Dr Patrick B. Iynedjian.
1992-1996 PhD student, Dept of Genetics and Microbiology, University of Geneva. Prof Stuart G. Clakson.
1996-2000 Post-doctoral fellow, Dept of Biological Sciences, Stanford University.Prof Philip C. Hanawalt
2001-2005 Life Sciences Research Associate, Dept of Biological Sciences, Stanford University, USA.
2005-2013 Assistant Professor/Lecturer, Institute for Cancer Studies, University of Sheffield, UK.
2013-2026 Chef de Clinique/Responsable Technique, Laboratoire de Diagnostic Moleculaire et Genomique, Geneva University Hospitals, Switzerland.
 

Teaching:

2003-2005 Invited lecturer in BioSci205 DNA Repair and Mutagenesis taught by Prof. Hanawalt, Dept of Biological Sciences, Stanford University.

2007-2009 Lecturer in MBB313 Genome Stability and Genetic Change, together with Dr Alastair Goldman. Department of Molecular Biology and Biotechnology, University of Sheffield.

2013-2025 Teaching two medical genetics courses to 1st year medical students, University of Geneva, Switzerland.

2013-2025 Teaching a pre-graduate genetic course in the unit Respiration.

2013-now Tutor in the problem-based learning unit Reproduction.

2015-now Tutor in the problem-based learning unit Croissance et vieillissement cellulaire.

2018-now Teaching a pre-graduate genetic course in the unit Croissance et vieillissement cellulaire.

2019 Teaching a post-graduate course on genetic risk calculations to FMH and FAMH trainees in Switzerland.

2019-2024 Teaching a pre-graduate genetic course to 3rd year biomedical students.

2019-now Tutor in problem-based learning unit Integration.

2025 Teaching a post-graduate genetic course for the CAS Laboratory Medicine.

 

Research Interests:

The early years

Having realized during my medical studies that I was fascinated by basic research, I undertook a MD thesis on a research topic. Dr Patrick Iynedjian had just cloned GCK, the glucokinase gene (this was before the human genome was sequenced and cloning a gene was a significant achievement) and I studied the regulation of the GCK promoter in primary rat liver cells.

 

For my PhD thesis with Professor Stuart Clarkson, I entered for the first time the field of DNA repair. Dr Daniel Scherly, a post-doc in Stuarts lab, had just accidentally cloned a human gene with strong homology to the yeast repair gene RAD2. I was able to show that mutations in this gene cause Xeroderma Pigmentosum, a DNA repair disorder characterized by deficiencies in the repair pathway known as Nucleotide Excision Repair (NER). I subsequently identified mutations in this gene in all known patients from XP complementation group G and the gene was therefore named XPG.

 

 

The Stanford years

I then moved to Stanford University, for a post-doc with Professor Phil Hanawalt (who discovered NER). There, I studied modulations of nucleotide excision repair (NER) in terminally differentiated cells: neurons, macrophages and myotubes.

 

I described a novel DNA repair phenotype in these cells, which downregulate NER genome-wide, except in the genes they are actually using. This phenomenon, which I named differentiation-associated repair (DAR), is distinct from transcription-coupled repair in that the later only operates on the transcribed strand whereas DAR repairs both strands.

 

I pursued this line of research as a Research Associate at Stanford, culminating with the discovery that the ubiquitin-activating enzyme E1 is a key control step underlying DAR.

 

 

The Sheffield years

I then led a small research group in Sheffield, consisting in two post-docs (Dr Nevila-Hyka Nouspikel and Dr Ross Drayton) and two PhD students (Wei-Ting Lu and Kimon Lemonidis, who both graduated brilliantly in 2011).

 

Together, we extended the study of DAR to:

       Temporarily quiescent cells: lymphocytes and hepatocytes.

       Stem cells: human embryonic stem cells and cancer stem cells.

 

We also further dissected the control mechanism involving E1 and investigated the potential roles of NER attenuation and DAR persistence in:

       Genomic instability.

       Tumorigenesis.

       Neurodegenerative disorders.

       Potential as a model system to study the early stages in carcinogenesis.

       Possible use to potentiate chemotherapeutic agents.

 

 

The HUG years

The return to my home country, Switzerland, in 2013 was the occasion of a major career change: I moved from basic research to a diagnostic genetics laboratory at Geneva University Hospitals.

 

Aside from routine (and not-so-routine) genetic testing, I developed an interest for cell-free circulating DNA and its clinical applications for:

       Cancer: Screening, remote genetic analysis of tumor cells (liquid biopsy), therapy validation and residual disease monitoring.

       Noninvasive prenatal testing: Not just for aneuploidy screening but also to detect familial point mutation in the fetus, from a maternal blood sample.

       Organ transplants: early detection of rejection.

 

Selected Publications:

Non-invasive prenatal diagnosis of monogenic disorders (NIPD-M)

Blouin JL, Rieubland C and Nouspikel T. Fetal Fraction Signatures: A Quality Control Tool to Detect Potentially Confounding Situations in NonInvasive Prenatal Diagnosis of Monogenic Conditions. Clin Genet. doi: 10.1111/cge.70121 (2025).

Schwitzgebel, VM, Blouin, JL, Dehos, B, Koehler-Ballan, B, Puder, JJ, Rieubland, C, Triantafyllidou, M, Zanchi, A, Abramowicz, M, and Nouspikel, T. Enhancing Fetal Outcomes in GCK-MODY Pregnancies: A Precision Medicine Approach via Non-Invasive Prenatal GCK Mutation Detection. Frontiers in Medicine 11:1347290(2024)

Fokstuen, S, Quteineh, L, Schwitzgebel, VM, Koehler-Ballan, B, Blouin, JL, Abramowicz, M, and Nouspikel, T. Noninvasive prenatal diagnosis of Mendelian disorders for consanguineous couples by relative genotype dosage. Clin Genet. 104:505-515. (2023)

Nouspikel, T, Blouin, J-L, Puder, JJ, Koehler-Ballan, B, and Schwitzgebel, VM. Precision medicine in diabetes: A non-invasive prenatal diagnostic test for the determination of fetal glucokinase mutations. Journal of Diabetes Investigation 13:256-261 (2022)

 

Circulating tumor DNA (liquid biopsy)

Nouspikel, T. Digging deep or spreading wide?a comparison of polymerase chain reaction and sequencing approaches in the analysis of circulating tumor DNA. Precision Cancer Medicine 3:13-21 (2020)

Koessler, T, Paradiso, V, Piscuoglio, S, Nienhold, R, Ho, L, Christinat, Y, Terracciano, LM, Cathomas, G, Wicki, A, McKee, TA, Nouspikel, T. Reliability of liquid biopsy analysis: an inter-laboratory comparison of circulating tumor DNA extraction and sequencing with different platforms. Laboratory Investigation 100: 1475-1484 (2020)

Friedlaender, A, Nouspikel, T, Christinat, Y, Ho, L, McKee, T, Addeo, A. Tissue-Plasma TMB Comparison and Plasma TMB Monitoring in Patients With Metastatic Non-small Cell Lung Cancer Receiving Immune Checkpoint Inhibitors. Frontiers in Oncology 10:142-149 (2020)

Koessler T, Addeo A, and Nouspikel T. Implementing circulating tumor DNA analysis in a clinical laboratory: a user manual. Advances in Clinical Chemistry 89:131-188 (2019).

Nikolaev, S, Lemmens, L, Koessler, T, Blouin, J-L, and Nouspikel,T. Circulating tumoral DNA: Preanalytical validation and quality control in a diagnostic laboratory. Anal. Biochem. 542: 34-39 (2018)

 

DNA repair in differentiated cells

Nouspikel T. Genetic instability in human embryonic stem cells: prospects and caveats. Future Oncol. 9:867-77 (2013).

Hyka-Nouspikel, N, Desmarais, J, Gokhale, PJ, Jones, M, Meuth, M, Andrews, PA, and Nouspikel, T. Deficient DNA damage response and cell cycle checkpoints lead to accumulation of point mutations in human embryonic stem cells. Stem Cells 30:1901-1910 (2012)

Lu, WT, Lemonidis, K, Drayton, RM, and Nouspikel, T. The Fanconi anemia pathway is downregulated upon macrophage differentiation through two distinct mechanisms. Cell Cycle 10:3300-3310 (2011)

Hyka-Nouspikel, N, Drayton, RM, Lemonidis, K, and Nouspikel, T. Circulating human B lymphocytes are deficient in nucleotide excision repair and accumulate mutations upon proliferation. Blood 117:6277-6286 (2011)

Nouspikel T. DNA repair in mammalian cells : Nucleotide excision repair: variations on versatility. Cell Mol Life Sci. 66:994-1009 (2009). Review.

Nouspikel T. Nucleotide excision repair and neurological diseases.DNA Repair 7:1155-67 (2008). Review.

Nouspikel, T. and Hanawalt, P.C. Impaired nucleotide excision repair upon macrophage differentiation is corrected by E1 ubiquitin-activating enzyme.Proc Natl Acad Sci USA. 103:16188-93 (2006).

Nouspikel, T. Hyka-Nouspikel, N., Hanawalt, P.C. Transcription domain-associated repair in human cells.Mol Cell Biol 26:8722-8730 (2006)

Nouspikel, T. DNA repair in differentiated cells: Some new answers to old questions. Neuroscience 145:1213-1221 (2007)

Hsu, P.H., Hanawalt, P.C., and Nouspikel, T. Nucleotide excision repair phenotype of human acute myeloid leukemia cell lines at various stages of differentiation. Mut Research 614:3-15 (2007)

Nouspikel,T. and Hanawalt, P.C. When parsimony backfires: neglecting DNA repair may doom neurons in Alzheimer's disease. BioEssays 25:168-173 (2003)

Nouspikel,T. and Hanawalt, P.C. DNA repair in terminally differentiated cells. DNA Repair 1:59-75 (2002)

Nouspikel, T., and Hanawalt, P.C. Terminally differentiated human neurons repair transcribed genes but display attenuated global DNA repair and modulation of repair gene expression. Mol. Cel. Biol. 20:1562-1570 (2000)

 

Role of XPG in xeroderma pigmentosum and Cockayne syndrome

Thorel, F., Constantinou, A., Dunand-Sauthier, I., Nouspikel, T., Lalle, P., Raams, A., Jaspers, N.G., Vermeulen, W., Shivji, M.K., Wood, R.D., and Clarkson, S.G. Definition of a short region of XPG necessary for TFIIH interaction and stable recruitment to sites of UV damage.Mol Cell Biol. 24:10670-80 ( 2004)

Lalle, P., Nouspikel, T., Constantinou, A., Thorel, F., and Clarkson, S.G. The founding members of xeroderma pigmentosum group G produce XPG protein with severely impaired endonuclease activity. J. Invest. Dermatol. 118:344-51 (2002)

Nouspikel, T., Lalle, P., Leadon, S.A., Cooper, P.K., and Clarkson S.G. A common mutational pattern in Cockayne syndrome patients  from xeroderma pigmentosum group G: Implications for a second XPG function. Proc. Natl. Acad. Sci. USA 94:3116-3121 (1997)

Nouspikel, T. and Clarkson, S. G. Mutations that disable the DNA repair gene XPG in a xeroderma pigmentosum group G patient. Hum. Mol. Genet. 3:963-967 (1994)

Scherly, D., Nouspikel, T., Corlet, J., Ucla, C., Bairoch, A., and Clarkson, S. G. Complementation of the DNA repair defect in xeroderma pigmentosum group G cells by a human cDNA related to yeast RAD2. Nature 363:182-184 (1993)
 

Glucokinase in primary rat hepatocytes

Nouspikel,T. and Iynedjian, P. B. Insulin signaling and regulation of glucokinase gene expression in cultured hepatocytes. Eur. J. Biochem. 210:365-373 (1992)

Nouspikel,T., Gjinovci, A., Li, S., and Iynedjian, P. B. Unimpaired effect of insulin on glucokinase gene expression in hepatocytes challenged with amylin.  FEBS Lett. 301:115-118 (1992)

Iynedjian, P. B., Pilot, P.-R., Nouspikel, T., Milburn, J. L., Quaade, C., Hughes, S., Ucla, C., Newgard, C. B. Differential expression and regulation of the glucokinase gene in liver and islet of Langerhans.Proc. Natl. Acad. Sci. USA 86, 7838-7842 (1989)

Iynedjian, P. B., Jotterand, D., Nouspikel, T., Asfari, M., and Pilot, P.-R. Transcriptional induction of glucokinase gene by insulin in cultured liver cells and its repression by the glucagon-cAMP system. J. Biol. Chem. 264, 21824-21829 (1989)

Last updated: February 2026