Northwestern Events Calendar

Oct
22
2018

"Understanding Breast Cancer Initiation in Single Cell Resolution"

When: Monday, October 22, 2018
4:00 PM - 5:00 PM CT

Where: Ward Building, 5-230, 303 E. Chicago Avenue, Chicago, IL 60611 map it

Audience: Faculty/Staff - Student - Public - Post Docs/Docs - Graduate Students

Contact: Liz Barrera Murphy   (312) 503-4892

Group: Department of Pharmacology Seminars

Category: Lectures & Meetings

Description:

The Department of Pharmacology Seminar Series welcomes our guest speaker:

Kai Kessenbrock, Ph.D
Assistant Professor
Department of Biological Chemistry
University of California, Irvine School of Medicine

Abstract:
The tissue microenvironment dictates adult stem cell behavior during normal homeostasis and cancer. Women with germline mutations in the breast cancer susceptibility gene BRCA1 (BRCA1mut) have high risk of developing the most aggressive, triple negative basal-type of breast cancer. Intriguingly, prophylactic mastectomy samples from BRCA1mut women show an expansion of progenitor cells at the pre-cancerous stage before loss of heterozygosity, indicating that pre-neoplastic changes and progenitor cell imbalances occur even before pathological conditions can be detected. Therefore, prophylactic mastectomy samples from BRCA1mut individuals provide an invaluable resource to identify alterations within the tissue microenvironment that contribute to increased cancer susceptibility and tumor initiation in humans. To this end, we utilized single cell RNAseq to sequence the transcriptomes of ~80,000 primary human breast tissue cells harvested from three control and three BRCA1mut carriers. This dataset enabled us to identify several previously unrealized molecular mechanisms mediating the communication between the cancer-susceptible breast epithelium and its surrounding microenvironment of stromal cells. We established an in vitro surrogate co-culture assay that allows us to functionally interrogate these interactions, manipulate specific pathways (e.g. using CRISPR/Cas9), and to measure and image pre-cancerous outcomes in epithelial cells. Understanding these microenvironmental control mechanisms and delineating previously unrealized pro-tumorigenic tissue constellations bear tremendous potential to develop accurate methods for cancer early detection and potential primary cancer prevention strategies.

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