CV Science

Nicolas Aznar Tumor microenvironment and cancer stem cells, PhD Molecular and Cellular Biology

Course and current status

• Current position (since January 2019) : CNRS researcher at Cancer Research Center of Lyon (CRCL), FRANCE (Dr. Renno's lab).

• (2017-2018): Postdoctoral training in Development, cancer and stem cells Laboratory at Cancer Research Center of Lyon (CRCL), FRANCE  (Dr Michelina Plateroti's Lab).

• (2011-2017) Postdoctoral training in Molecular and Cell Biology and Biochemistry Laboratory at University of California, San Diego, USA (Dr Pradipta Ghosh's Lab).

• (2006-2011) PhD student in Molecular, Cellular and Cancer Biology at University of Lyon, FRANCE (Dr Marc Billaud's Lab). 

Scientific summary

Colorectal cancer (CRC) is the third most commonly diagnosed cancer in both men and women worldwide. Although some colorectal cancers are effectively treated through the standard strategy of surgery, radiation and/or chemotherapy, some patients have a recurrence of their cancer and a spread to other parts of the body that threatens life. Despite decades of research, we are unable to predict which cancers will be effectively treated and which are likely to spread. Besides the deadly affliction that cancer is at individual level, there is an urgent need to find new or better treatment alternatives for colorectal cancers. 

Intestinal stem cell (ISC) biology (i. e. self-renewal and multipotency) relays in a complex crosstalk within the niche at the level of crypt cells between signaling pathways modulated by growth factors, nutrients, hormones, oxygen and mechanical stress. Moreover, dysregulation of the SC niche homeostasis has been extensively shown to play a crucial role in malignancies and tissue degeneration. In particular, studies on the human ISC niche have shown that dysregulated colonic crypt dynamics cause SC overpopulation and initiate colon cancer. In support of the well-documented resistance of Cancer SCs (CSCs) to conventional therapies, high SC signature scores statistically associate with a high risk of tumor relapse in patients. Targeting CSCs constitute a determinant medical issue and identify novel players of SC plasticity is a prerequisite to open novel therapeutic avenues. 

In this context, my group is investigating SCs interactions with their microenvironment or “niche” and how dysregulation of this interface could influence CSCs resistance to conventional therapies. Using a novel integrative approach that couple 3D spheroid cell lines, innovative ex vivo organoid/tumoroid cultures as well as next generation interactome mapping in 3D context, the outcomes of our work could have the potential of identifying new biomarkers and effective therapeutic strategies in a given patient defining a new avenue for stratified therapy in CRCs.

Group expertise:

1) biochemistry and cell biology.

2) modeling in-vitro physiopathology context: 2D and 3D culture in niche-like microenvironment (microfluidic associated to spheroids, organoids and tumoroids) from cell lines, genetically-modified mouse models and human samples.

3) Innovation and technology development: invention and development of the STEMNESS^TM technology : state of the art 3D culture system.

4) private-public collaborations and co-development.