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BCRF Investigator Since

2015

Area(s) of Focus

Gurinder S. Atwal, PhD

Assistant Professor of Quantitative Biology
Cold Spring Harbor Laboratory
Cold Spring Harbor, New York
EIF/Stand Up To Cancer

Current Research

  • Studies are aimed at improving the effectiveness of immunotherapy by studying the tumor ecosystem.

  • A Stand Up To Cancer Convergence team applies a multi-disciplinary approach to tumor biology.

  • This collaborative research will lead to novel treatment approaches that modify the tumor environment to improve anti-tumor immunity and response to immunotherapy drugs.

Tumors consist not only of cancer cells, but also stromal and immune cells that constitute the tumor microenvironment (TME). The TME is an ecosystem of multiple cell populations, and the extracellular matrix (ECM) that they produce, that interact in a complex fashion to yield tissue form and function. 

Cancer cells can take on dramatically different properties based on influences from the microenvironment. In many different cancer types, including breast cancer (BC), tumors with more stromal cells typically have worse clinical outcomes. In contrast, tumors infiltrated by a type of immune cell called CD8 T cells have better clinical outcomes. Hence, tumors behave differently based on the collective behavior of the microenvironment. 

The objective of the Stand Up 2 Cancer (SU2C) Convergence team consisting of Drs. Atwal, Irvine, Lee, Levine and Yu is to apply systems and ecological approaches to study the TME and determine whether it is an important determinant for the efficacy of cancer immunotherapy. 

The SU2C team brings together expertise in high dimensional histology, image analysis, culturing cells from primary human breast tumors, 3D spheroids, bioinformatics, ecology modeling, and nanotechnology to study the ecology of the TME in BC, and develop therapeutic and imaging applications.

In the first year of their award, the SU2C team showed that cancer-associated fibroblasts and other immune-derived cells interact with cancer cells to promote tumor progression and metastasis. They also found the addition of a commonly used drug to treat parasitic infection improved reponsed to anti PD-1/PD-L1 immunotherapy.

They are continuing these investigations to understand the relationship between the stromal cells and cancer cells and develop targeted approaches to improve response to treatments.

Bio

The biological landscape is made up of a vast and dizzying number of variables that interact in complex and often seemingly random ways. The Atwal lab at Cold Spring Harbor Laboratory is applying principles from physics and computational sciences to understand the tsunami of data generated from new DNA sequencing technologies in order to understand the evolutionary forces at play on the genome and to understand the genetics of some human diseases, including cancer, infertility and neuropsychiatric disorders. In the past, they have analysed the genomes of thousands of individuals and modeled the process by which genetic variants have evolved in the last 100,000 years of human history. This has led to the discovery of new mutations that increase the risk of breast and ovarian cancers and a surprising connection with female infertility. Recently, they have begun to focus efforts on understanding tumor heterogeneity and evolution by analysing whole genome sequences from single tumor cells.

Co-Investigators