Marina ShkreliInstitut de recherche sur le cancer et le veillissement de Nice (IRCAN) - CNRS / Inserm / Université Côte d’Azur
Mes recherches
After completing my PhD training in December 2006 (INRA Nouzilly, France), I joined Stanford University School of Medicine as a postdoctoral scholar in January 2007 (California, USA). During my postdoctoral training, I studied the role of telomerase in adult stem cell regulation in the laboratory of Steven Artandi. I have then been awarded with an ATIP-Avenir grant in 2012 that allowed me to set up and lead my own research group since January 2013 at the Institute for Research on Cancer and Aging of Nice (IRCAN). In 2014, I obtained a tenured position (CR1) at the Inserm.
The projects developed in my team aim to understand telomerase functions in regeneration, and in cancer and to understand how aging modulates telomerase activities. In particular, we found that telomerase activates a latent regenerative program in the adult mammalian kidney. The objectives of my team are (1) to characterize the progenitor cells that support this regenerative program and to determine how aging restrains pro-regenerative functions of telomerase, (2) to characterize the molecular events targeted by telomerase in cancer initiation and progression, and (3) to understand how telomerase functions are modulated at the molecular level. To answer those questions, we use sophisticated genetic approaches in vivo combined with original in vitro approaches. The long-term goals of our effort are to understand how pro-regenerative functions of telomerase can be fostered to restore organ function following injury, and to determine how non-canonical functions of telomerase can be modulated to restrain cancer development.
Mon projet ATIP-Avenir
Understanding the role of telomerase in tissue homeostasis, repair and in cancer development
Telomerase serves two independent and critical roles in normal stem cells and in cancer. As a reverse transcriptase that synthesizes telomere repeats, telomerase maintains telomere length and stability to prevent the severe adverse consequences of telomere dysfunction.
In addition to this well documented telomerase activity, several studies demonstrated that the telomerase protein component TERT possess a non-canonical activity, that facilitates proliferation of quiescent epidermal stem cells. Moreover, TERT causes a dramatic effect on kidney epithelium, resulting in reversible cell cycle entry. These observations have led me to hypothesize that kidney epithelium in fact possess significant regenerative capacity, a potential revealed by activation of a telomerase signaling pathway. In this project, I proposed to investigate the cellular mechanism involved in TERT-induced kidney regeneration.
Cancer cells possess the same properties as stem cells and cancers are increasingly regarded as a pathological aspect of stem cell biology. The results indicating that TERT regulates stem cells proliferation therefore motivated my desire to study the impact of this newly identified function of TERT on cancer cells. In this aim, I proposed to determine if and how non-canonical activity of TERT impacts tumorigenesis