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Jean-Philippe Theurillat



Prof. Jean-Philippe Theurillat studied medicine at the University of Zurich, where he obtained in 1999 his federal diploma in human medicine. He specialized first in internal medicine and then in surgical pathology at the University Hospital in Zurich and at the CHUV in Lausanne followed by the board certificate in pathology in 2007. In 2008, he worked as a postdoctoral fellow in the group of Prof. Wihlem Krek at ETH: the researcher discovered the molecular mechanisms of a novel oncogene involved in ovarian and liver cancer that favours the survival of cancer cells and mediates resistance against current pharmacological therapies. In 2011, the researcher joined the group of Prof. Levi Garraway (Boston) to train in next-generation DNA technologies and translational oncology. He worked most notably on the functional characterization of new identified oncogenes and tumor suppressors in prostate cancer. In 2014 he received a professorship grant from the Swiss National Science Foundation, which enabled him to pursue his studies at IOR, where he continuous his work on a new genetically defined subtype of prostate cancer. His investigations aim to elucidate the biological function of new mutations in order to establish innovative therapeutic avenues. The researcher has published contributions in many leading scientific journals such as Nature Medicine, Science and Cancer Cell. His work has been recognized by various prizes, including the Pfizer Research Prize in Oncology in 2012 and the Astellas Award in 2017. From 2019 Prof. Theurillat also involved in student teaching as tenured professor at the new biomedical faculty of USI.


 Research Focus

Cancer is driven by cardinal genetic alterations that activate driver genes. Driver mutations are not only essential to initiate tumorigenesis but are also required for tumour growth and maintenance. This raises the possibility to target these mutations, opening more specific, therapeutic opportunities to treat cancer patients. The research group focuses on new drivers of prostate cancer. The team aims to explore the roles of these genes in tumorigenesis with the ultimate goal to develop new therapeutic avenues for patients suffering from prostate cancer. The group identified with TRIM24 a new transcriptional regulator involved in advanced, castration-resistant disease that sustains the activity of the androgen receptor – a key lineage-specific onco- gene in this setting. Currently, we are developing and testing small molecule-based degraders of TRIM24 in preclinical models of castration-resistant disease. In addition, we are dissecting the genetic basis of the vulnerability of prostate cancer cells to low and high levels of androgens to improve patient treatment in the clinic on the long term. We have recently published that pre-existing founder mutations in SPOP and ERG influence the response to low and high levels of androgens because these mutations require and trigger at different level of androgen receptor signaling for optimal growth. Moreover, we were able to validate our hypothesis using published clinical und molecular expression data sets. Our promising data could help to identify patients that could either respond preferentially to low or high levels of androgens. In recent years, the group discovered that highly recurrent driver mutations in SPOP are loss-of-function in prostate cancer while similar but not identical mutations in endometrial cancer exert gain-of-functions. In a follow-up work with the group of de Vries in the Netherland, we have now published that there are patients with corresponding de novo germline mutations in SPOP that develop distinct neurodevelopmental disorders depending as to whether the mutations are gain- or loss-of-function. Recently we assembled the thus far largest transcriptional atlas for prostate cancer which includes data sets of human primary and metastatic prostate cancer. Using this resource (pcaprofiler.com), we have more recently identified alternative pathways to disease progression with distinct molecular features including chromatin and DNA modifications that are targetable by small molecule inhibitors in the clinic. The work is currently under consideration for publication. Based on these insights, we are currently developing combination therapies aimed to prevent disease progression under androgen deprivation therapies in high-risk prostate cancer patients

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