Mohit K Jolly's Talk

Apr 07, 2016 - 17:00

Apr 07, 2016 - 18:00

Room 118 Department of Chemical Engineering

Seminars

Mohit K Jolly RICE University USA

Abstract: Metastasis spread of cancer cells from one organ to another claims 90% of all cancer-related deaths and remains clinically insuperable. To leave the primary tumor cancer cells lose cell-cell adhesion and gain migration and invasion to enter the bloodstream – a process called Epithelial to Mesenchymal Transition (EMT). Upon reaching a distant organ they regain cell-cell adhesion and lose migration – a process called Mesenchymal to Epithelial Transition (MET). I will present an integrated theoretical and experimental approach that elucidates how cancer cells undergo EMT and MET and how these transitions affect the ability of cancer cells to initiate new tumors at a distant organ. By mathematically modeling the core genetic circuit that regulates EMT/MET we predicted that in addition to being epithelial (no migration high adhesion) and mesenchymal (high migration no adhesion) cancer cells can stably adopt a hybrid epithelial/mesenchymal (E/M) state (both migration and adhesion) too that enables them to migrate collectively. We also identified how cancer cells maintain their hybrid E/M state; these predictions were later validated in experiments on H1975 lung cancer cells. Finally by modeling the EMT/MET circuit with that responsible for tumor-initiation ability we predicted that cells in a hybrid E/M state can form much more tumors as compared to mesenchymal cells a prediction that is corroborated by recent experimental and clinical data in many cancers. Our integrated experimental-theoretical approach identifies multiple advantages that a hybrid E/M state offers during cancer metastasis and tumor initiation and proposes novel potential targets that can disturb collective migration of cancer cells and push them out of this hybrid E/M state thereby halting metastatic progression. Layman’s abstract: 90% of all cancer related deaths happen because cancer spreads to different organs of the body. Cancer cells spread by leaving the primary tumor individually or collectively entering the blood circulation to travel throughout the body and exiting at distant organs to seed new tumors there. How do cancer cells leave the tumor? When they leave what prepares them to survive in a distant ‘foreign’ organ and start new tumors there? I will present how wet-bench experiments can be integrated with mathematical models of genetic networks regulating cancer cell migration to foster a new understanding of these clinically relevant questions. We show that how can cells move collectively stably and how can their collective migration be disturbed. We also indicate that cells moving collectively are more likely to start a new tumor a prediction that is supported by recent experimental and clinical data. Our results offer a predictive quantitative framework to understand cancer cell migration and propose potential targets to curb metastasis.About the speaker: Mohit is a graduate student in Department of Bioengineering at Rice University with research interests in cancer systems biology - integrating mathematical models of cellular behavior with wet-bench experiments to elucidate the principles of cancer progression. He graduated with a B. Tech. (2010) and M. Tech. (2012) in Biological Sciences and Bioengineering from IIT Kanpur. https://scholar.google.co.in/citations?user=6fK8E-gAAAAJ&hl=en