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Gurinder S. Atwal, PhD
Assistant Professor of Quantitative Biology
Cold Spring Harbor Laboratory
Cold Spring Harbor, New York
EIF/Stand Up To Cancer
- 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 approaches that modify the tumor environment to improve prevention and treatment outcomes.
Tumors grow in a diverse environment comprised of a variety of cells types, which make up the tumor microenvironment – TME. This environment can either promote or suppress tumor growth, but often times, tumor cells co-opt normal cells to their advantage. The Stand Up to Cancer/BCRF project team utilizes a variety of technologies and research approaches to understand the interactions between tumor cells and normal cells to identify potential therapeutic and prevention strategies.
Full Research Summary
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.
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 breast cancer and develop therapeutic and imaging applications.
During the course of the BCRF-supported research, the SU2C team profiled stromal cells and epithelial cells from normal breast reduction samples. By comparing the profiles of normal cells from BRCA1 carriers to non-BRCA carriers, they found early changes in cell compositions as well as molecular alterations in the mammoplasty reduction tissues of BRCA1 carriers.
In the coming year, they will identify factors that promote the proliferation of mammary epithelial cells from BRCA1 carriers and test which pathways are critical for malignant growth.
These studies will help underscore players involved in the heterogeneity of BRCA1-associated breast cancer as well as the identification of potential targets for cancer intervention.
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.