Exploration of a Novel Differentiation Axis in Dormant Breast Cancer Cells




Professor of Cancer Biology

Project Summary

Summer Research Experience
Spending this past summer studying breast cancer in the lab of Dr. Lewis Chodosh has been absolutely phenomenal. Understanding how breast cancer cells that are refractory to initial treatment survive, proliferate and seed lethal recurrences is vital for developing a reliable cure to ensure the health and well-being of survivors. During my summer in the Chodosh lab, I dedicated my time to understanding tumor cell survival and entrance into a non-proliferative state, a state that typically precedes recurrent tumor outgrowth. 
Working with genetically engineered breast cancer cells, I was able to delve into the mechanisms of “dormancy” and study how the cells would survive if certain genes were removed using CRISPR/CAS9 technology. The genes I targeted were known for their role chondro/osteogenic differentiation (bone and cartilage development), as past research had surprisingly indicated thatthey may play a significant role in dormant cell survival. Therefore, I hoped that removing these genes would impair cellular differentiation and survival while in dormancy. 
In the lab, I worked with the cells and performed various assays to test their viability, growth, proliferation, and differentiation. This included determining cell number through fluorescence intensity, cell death through caspase activity, alkaline phosphatase levels to assess chondro/osteogenic differentiation, and staining the cells to observe colony formation throughout a 28-day dormancy time course. Of course, I had the opportunity to perform a Western Blot and qPCR to ensure proper deletion of my targeted transcription factors, as well as look at potential downstream targets. 
Alongside performing assays, I did significant scientific data analysis using excel (which I had zero previous experience with). I created graphs, performed statistics, and made a comprehensive power point presentation to depict the data – loads of data – compiled over the course of the summer.  We were able to conclude that not only did our targeted genes (SOX9, RUNX2, and VDR) have an impact on cellular viability, but a relationship between SOX9, VDR, and their downstream targets that is of interest for further studies. 
Working alongside Dr. Amulya Sreekumar, I was actively engaged in her research, learning how to efficiently perform assays and embrace the mentality of a scientist. I learned that doing research is more than asking questions and running tests; it’s about understanding and interpreting the data to figure out the next logical step and drawing the right conclusions to work towards discovery. My contribution this summer is just a morsel of the work that is done in the lab. However, I am elated that I could contribute to the study of breast cancer because of its impact, and the invaluable lessons I learned from my mentor and those in the lab who were exceedingly supportive. It was a wonderful experience that I am more than grateful to have had, and one that I sincerely hope others will.