Research Project

Modeling tumor-stroma crosstalk in lung cancer to identify targets for therapy

Overview

Program Title

Modeling tumor-stroma crosstalk in lung cancer to identify targets for therapy

Principal Investigators

Stephen T.C. Wong, PhD
Vivek Mittal, PhD

Lab Websites

http://www.methodisthealth.com/SMB
http://www.mittallab.org/

Project Description

Our research is aimed at finding molecularly targeted therapies for the treatment of non-small cell lung cancer (NSCLC). Taking into account the emerging paradigm that the reprogrammed intratumoral stromal cells contribute to carcinogenesis, we are employing integrated experimental and computational approaches to identify tumor-stromal crosstalk pathways that drive NSCLC progression in mice and humans. We are developing a multicellular crosstalk signaling network modeling and visualization tool, which is being applied to multicellular RNAseq data to identify tumor-stroma crosstalk pathways. Genes involved in these signaling mechanisms constitute potential candidates, which are being validated in rapid in vitro coculture assays, and their mechanistic and therapeutic potential is being assessed in genetically engineered NSCLC models. This study explores the relatively understudied tumor-stroma crosstalk pathways as a largely untapped source of drug targets. It has tremendous potential for the development of novel therapeutic strategies that will target tumor-stroma interactions and may complement existing treatments that target cancer cells.

To date, we have developed a computational model, P2GWAS, to identify both autocrine and paracrine pathways. We have made significant progress in refining our crosstalk discovery algorithms and developing a graphic interactive interface for crosstalk signaling network discovery. Early results have indicated roles for the HGF-MET pathway and the OPN pathway, for which we have made significant progress in experimentally assessing their tumor-stroma crosstalk contributions both in vitro and in vivo.

Investigators

Principal Investigators

Dr. Stephen Wong

Dr. Stephen Wong is the founding Chair of the Department of Systems Medicine and Bioengineering at Houston Methodist Research Institute, Director of Translational Research at Houston Methodist Cancer Center, and Professor at Weill Cornell Medicine. He has three decades of research experience in informatics, imaging, artificial intelligence, and systems biology. His research has led to a number of clinical trials for drug repositioning and image-guided intervention in cancer, he developed a digital Picture Archiving Communication System (PACS) for hospitals, and he has published over 500 peer-reviewed papers. He holds eight patents in informatics, imaging, and drug discovery.

Dr. Vivek Mittal

Dr. Vivek Mittal is the Professor and Director of the Neuberger Berman Lung Cancer Laboratory at Weill Cornell Medicine. His research is focused on understanding the cooperative heterotypic reciprocal signaling between the stromal elements of the microenvironment and tumor epithelial compartments. His research has produced several patents and has been published in top peer-reviewed journals, including Science, Nature, and PNAS.