Hey there! I’m Hassan Samiullah, a rising 12th Grader at Portola High School in Irvine, CA.
It took less than a day after the start of my internship at Cedars-Sinai through CIRM SPARK for me to be soaked in medical jargon. Indeed, my research under the mentorship of Dr. Katie Grausam of the Breunig Lab will focus on an intersection of neuroscience, cancer, stem cells, and molecular biology. While it is tempting to read over these words and dismiss them as being big words just for scientists (and/or nerds), I hope you can appreciate how they fit together like pieces of a puzzle.
Glioblastoma is a deadly type of cancer affecting glial cells—cells that support your brain’s neurons. Before testing any treatment against this cancer, scientists need tumor cells to work with. Enter GL261: a glioblastoma cell line originating from an experiment done over 80 years ago. In 1939, Dr. Arnold Seligman and Dr. M.J. Shear injected into mice a cariogenic substance called methylcholanthrene (try pronouncing that), sure enough causing brain tumors in 65% of the mice. Those tumor cells were preserved and have been used for research ever since. Cells from that very line glowed bright green on my laptop screen (as they were transfected by Dr. Grausam with mClover/GFP that inserted into the DNA) . I’ll get to see a mouse undergo brain surgery and be injected with those luminescent tumor cells (I’ll get the best seat in the house with Microsoft Teams), hopefully resulting in a tumor we can use for testing treatments. But just like all things in medicine (and in life), the mouse tumor model has limitations. Tumor cells from the GL261 line have mutations (changes in DNA that can lead to diseases like cancer) in the RAS and p53 genes. While p53 is a widely studied gene in cancer research, it turns out that RAS doesn’t commonly mutate in human glioblastomas: a study from 2013 found a mutation rate of just 1%.
Having mice tumor models that are like human tumors can make a study’s results more externally valid. Plus, it’s always good to have more data to work with. But is a different model possible? Enter plasmid DNA. It’s genetically engineered DNA that has mutations in genes similar to ones that can occur in human glioblastomas. I watched a laborious process of gene cloning to produce many of these plasmids, which are now being grown in bacteria, and which will hopefully be ready to give a mouse a tumor (this will involve electroporation: pretty much shocking cells so that plasmid DNA can pass through their membranes). I’m really excited to see how the two experiments will play out, namely how the GL261 tumor will compare with the plasmid DNA-induced tumor. Our overall goal is to see how the immune system interacts with tumors to affect not just the cancer itself, but also the environment around it, which can hopefully give us a better insight into how treatments can be more effective. Dr. Grausam has done a great job explaining her lab work and how it fits in to the bigger picture of fighting cancer, no matter how complicated the steps may be. I’m thankful for having her expertise, support, and feedback. I look forward to what we can learn and accomplish!
RMI CIRM SPARK 