Principal Investigator


Professor of

Clinical Medicine


  Research Topics • Developmental biology
• Diabetes pathophysiology
• Human sex development
  Subtopics • Disorders of sex development
• Genetic of pancreatic diseases and autoimmunity

Questions addressed

► 1. Insights in sex development
Defects of sexual development (DSD) are not rare, having a prevalence of 1:4500, and an increasing interest by the media and the public. Elucidation and clarification of defects of sexual differentiation is essential for the improvement of care and management of patients affected by these anomalies. A precise diagnosis would render decisions regarding surgical and medical treatment prompter and easier, and would prevent unnecessary physical and psychological stress for patients, families and health providers A deeper understanding of these conditions will have impact on the quality of life of the patients and their families, with clear benefit for the community.
My group is one of the very few in Switzerland enjoying national and international recognition in this field. We described two new clinical entities leading to DSD in patients, the WNT4 deficiency (the Biason-Lauber syndrome) and CBX2 defects. After the demonstration that WNT4 is one of the few known elements necessary for proper sexual development in women, we should now study a large series of carefully characterized patients-in relation to the development of Müllerian and Wolffian ducts, renal anomalies, ovarian morphology and androgen secretion. WNT4 should now be added to the list of genes such as SRY, SOX9, WT1, DAX1, SF1 and 3αHSD, whose study in isolated cases of sex reversal has contributed a number of pieces to the jigsaw puzzle of human sexual development. Indeed, perhaps it will be possible to dispense with the unfortunate truism that the female represents the default pathway in mammalian sexual development. On the other hand, given the role of WNT4 in ovarian androgen production, its gene is a good candidate in the pathophysiology of functional ovarian hyperandrogenic states, such as polycystic ovary syndrome, a condition affecting 5-8% of the reproductive aged women and it is the leading cause of anovulation and infertility. We could recently add CBX2 to the jigsaw puzzle of sex development. Besides the advantages of a precise DSD diagnosis, studies on the role of CBX2 will shed more light on testicular and, most interestingly, on ovarian development, a terrain still relatively unexplored. Clinically, if the similarity between mouse and human phenotype remains throughout life, unexplained sterility or premature ovarian insufficiency in women might be a unique sign of CBX2 abnormalities in the human population.
Also, our present SNF financed studies by identifying new pathways in hormone synthesis and action may provide new targets for pharmacological intervention for states of androgen excess, such as polycystic ovary syndrome and 21-hydroxylase deficiency, and for androgen-dependent hyperplasias and malignancies. We are confident to be able to identify new elements crucial for ovarian development and gain insight on ovarian physiology and disease, e.g. premature ovarian insufficiency.
► 2. Genetic Studies in Diabetes
The reward of the genetic studies will be two-fold: increased understanding of the causes of DM, facilitating the creation of preventive therapies, and possibility of predicting which patients are predisposed in order to target them for preventive therapies.
Recently, in collaboration with the group of Prof. Marc Donath (University of Basel) we took advantage of our expertise in the diagnosis of human genetic diseases to study a family with several cases of type 1 diabetes. Type 1 diabetes is typically diagnosed in lean, young individuals displaying hyperglycemia and markers of autoimmune-mediated β-cell destruction leading to insulin deficiency. The class III histone deacetylase SIRT1 has been shown to play an essential role in modulating many age-related diseases. We described a family carrying a mutation in the SIRT1 gene, in which all five affected members developed an autoimmune disorder: four type 1 diabetes and one ulcerative colitis. Direct and exome sequencing identified a mutation in SIRT1 leading to overproduction of nitric oxide, cytokines and chemokines in β-cells. These observations identify a novel role for SIRT1 in human autoimmunity and unveil a monogenic form of type 1 diabetes. With regard to research on child health, knowledge about specific genetic risk might help to clarify risk processes. On the other hand, the research has focused on behavioral changes that may protect some children from environmental insults, overlooking the potential protective role of genes. Genes are assumed to create vulnerability to disease, but from an evolutionary point of view they are equally likely to protect against environmental insults. Knowledge of protective genes will prevent the application of (psychologically and economically) costly unnecessary preventive measures.

  Keywords • Autoimmunity
• Diabetes
• Human Sex development
• Metabolic control
  Contact Email address anna.lauber [at] unifr.ch  
  Personal site http://www.unifr.ch/endocrinology   


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