Christian KranjecUniversity of Cambridge, Department of Pathology, Cambridge, England
Biography
Christian Kranjec was born in Trieste, Italy. He conducted his University studies at the University of Trieste and subsequently at the University Paris 7 Denis Diderot in Paris. He joined the PhD program at the International Centre for Genetic Engineering and Biotechnology(ICGEB)in Trieste where he worked with Dr.Lawrence Banks on the molecular biology of cervical cancer associated with human papillomavirus(HPV)infection. This also gave him the opportunity to fully experience and appreciate working in an international context. After completion of his PhD studies, he moved to Cambridge, United Kingdom, where he joined the laboratory of Prof. John Doorbar. His current research focuses are the
investigation of mechanisms of HPV-Â?induced neoplasia in stratified
epithelia and the understanding of the molecular basis behind the
susceptibility to neoplastic transformation of the cervical epithelium. In its free time he enjoys hiking,travelling to destinations allowing contact with local nature, winter sports and a glass of good wine.
Research Interest
Novel breakthroughs in the field of epithelial cell biology shed light on the regulation of stratified epithelia. The phenomenon of cell differentiation at these sites can be seen as an extraordinary
evolutionary adaptation of keratinocytes against the accumulation of mutation within the tissue. In this complex system, the numbers of cells generated by proliferation and lost by differentiation are
balanced, therefore ensuring the maintenance of the tissue homeostasis. If a mutation reduces the fitness of a cell compared to their wild type counterparts, this will be induced to differentiate, shed from the tissue and ultimately replaced with a ?new? cell generated by the cell proliferation ongoing in the deepest layers of the epithelium. In this scenario, the induction of neoplasia can then also be considered under a Darwinian evolution point of view. That is, if a cell accumulates mutations
affecting the function of key ?driver? genes, for instance implicated in the regulation of cell proliferation and/or differentiation, this can confer a competitive advantage to mutant cells promoting their long-term maintenance and clonal expansion in the tissue; ultimately increasing the risk of accumulation of oncogenic mutations. In our lab we try to integrate the increasing knowledge about the regulation of squamous epithelia homeostasis with events characterizing early stages of the HPV life cycle as well as HPV-driven neoplasia. Compelling evidence suggest that HPV types infecting mucosal tissues, such as HPV-16, evolved the ability to inactivate driver gene products, such as p53 and Notch1, as a strategy to modulate the differentiation of infected keratinocytes and promote their persistence within the epithelium.
An additional area of increasing interest in my research is the investigation of abortive sites of HPV infection (i.e. those sites particularly susceptible to viral life cycle deregulation and cancer development), with a particular focus on the uterine cervix. The cervix, along with other anatomical sites in the human body, presents a transformation zone in which two different types of epithelia (i.e. squamous and columnar) join forming a distinct microenvironment. Indeed these sites are believed to sustain the existence of stem cells, possibly giving rise to both squamous and columnar epithelial cell lineages. The identity of these progenitor cells is still elusive, however previous studies suggested that the expression of particular patterns of keratins as well as of the transcription factor p63 identifies them. In addition, these progenitor cells are also believed to be sites for abortive HPV infection. Our aim is to define the molecular signature of this cell population, in order to understand its susceptibility to HPV-mediated transformation. To this goal we are
developing approaches involving the use of animal models, 3D-tissue culture systems as well as the analysis of human clinical samples.