Hello readers! Welcome to Week 2 of my science blog about my research experience. This week I get to talk about the science that my lab is exploring as well as my specific project. To start, I’ll begin with some background:
Lung cancer causes the most deaths per year out of all cancer types. Nearly 150,000 men and women are projected to die due to lung cancer in 2019 in America alone (American Cancer Society). Furthermore, lung to brain metastasis (the spreading of cancer from the lung to the brain) is a common occurrence and particularly poor prognosis for patient survival. My lab studies the mechanisms of brain metastases by exploring the signaling machinery that goes awry in cancer. We are focusing on a specific kinase (a protein that causes chemical shifts in other proteins, acting like a master signaler) and its role in metastasis. Jake and I are using a line of cancer cells that naturally metastasize to the brain for our research. Jake made this line earlier by injecting cancer cells into the hearts of mice, isolating tumors that spread to the brain, and repeating this process until the cancers reliably migrated to the brain. I think that’s a really elegant way to design a cancer line that is specific to our research.
As far as my research goes, I am dividing my work into two projects. For one of the projects, I am replicating a number of experiments that Jake completed earlier in a different cell line. His results were really promising, and it would help the story immensely if we could show the same effects in a lung cancer cell type with a different “driver” mutation (the major contributor to the tumorigenic phenotype). This project is fairly straightforward since the path has already been laid out, and the process is going smoothly so far.
My second project is much less structured, at least so far. Earlier, Jake compared RNA sequencing data between our metastasizing cancer line and the “parental” line (the same cancer line without the repeated intracardiac injections) to find a list of about 100 genes that appeared to be upregulated in the metastazing line compared to the parental line. Jake and previous students explored some of these genes, but most of them haven’t been analyzed yet. My project is to pick some of these unexplored, upregulated genes and perform tests to determine their levels of upregulation, impact on metastasis, and any interesting new pathways they may be involved in. I chose about 30 of the genes and designed PCR primers for all of them in order to perform an RT-qPCR experiment to quantify their levels in the metastasis line and parental line. The preliminary results were really interesting. In fact, one of the genes appears to be upregulated over 70 times in the metastasis line! Multiple other genes were also upregulated, usually on the order of 2-4 times. These results will need to be repeated to confirm their legitimacy, but my next step is to focus on these genes and figure out why they are upregulated. My plan is to look at the transcription factors linked to these genes and try to trace a path back to the kinase we are focusing on. That would make a cool story!
I am really excited about my work so far. While I have run into speed bumps in different experiments on different days, in general the projects are going smoothly. I really hope I can make a significant contribution to Jake’s work and the work of the other members of the lab. Even if the data I collect doesn’t show anything interesting, I am still learning so much about the daily life of a researcher and what it means to be exploring cancer. Next week I will interview the PI of my lab, Dr. Pendergast, and share that here. See ya next week!
-Brennan
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