This is the first in a series of blog posts written by some of the UVM College of Medicine 2016 Summer Research Fellows.
After three years of working in research laboratories after graduating from college, first as a research technician at MIT studying targeted therapies for lung cancer, and then working at a small biotech company in New Hampshire producing monoclonal antibody therapeutics, I had gotten used to pipetting all day, running PCRs and western blots and spending hours at a tissue culture hood plating cells. And I loved it! In both jobs, it was fascinating to work with the mechanisms behind disease, manipulating mutations and signaling pathways to combat disease in the laboratory setting. But curing cancer in a petri dish is very different from curing cancer in a patient. While I loved the lab work, there was something missing. Pipetting all day and analyzing rarely heard of proteins, it was easy to lose sight of the ultimate goal: to make a drug that cures people of disease. I decided to come to medical school because I didn’t want to be behind the scenes anymore. I wanted to be at the bedside, in the exam room, talking with patients, witnessing first-hand the ultimate goal of scientific research.
The summer between your first and second years is the only summer you have off in medical school. I missed conducting research, so I took the opportunity to get back to it. There is such a variety of groundbreaking research occurring here at the University of Vermont that it was relatively easy to track down a lab working on what I was interested in, lung cancer. I soon met and wrote a research proposal for a summer research fellowship with Dr. Jos van der Velden, who is currently studying non-small cell lung cancer. However, this time around, I wasn’t just going to sit at the bench all day. I was going to see the whole picture of translational research, working both at the lab bench and in the clinic. Dr. van der Velden is collaborating with a critical care and pulmonology doctor, Dr. Matt Kinsey, who is leading a study to obtain additional biopsies from lung cancer patients who have provided consent to have additional tumor tissue collected, which will then be studied in the research laboratory.
The whole process begins by meeting the patient in the weekly lung multidisciplinary clinic, where patients with suspected lung cancer are sent. Most of these patients have had a suspicious lung mass spotted on a CT or PET scan and now need a biopsy to identify if the mass is cancer and if it is, to stage the cancer. The biopsy procedure is discussed, and a procedure date set. The tissue is obtained through endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA). A bronchoscope is inserted down the airway and samples from suspicious looking lymph nodes and masses are collected. Cytopathologists are in the room, looking at the samples collected from each suspicious area and giving Dr. Kinsey real time information on whether the sample contains cancer cells, inflammatory cells or normal tissue.
If a sample is obtained that is believed to be cancer, and the patient provided consent to be part of the study, an additional sample is collected to be brought back to lab. Although cancer cells have no problem proliferating in the human body, culturing them up in lab can be a bit more challenging. They can be contaminated with bacteria, which can take over the culture. They can grow incredibly slowly. And if only a small amount of cancer cells were collected compared to non-cancerous tissue, the non-cancerous cells can take over. To make sure what we are growing is cancer, we look at tumorigenic properties, such as migration, proliferation and invasion by growing the cells in various media, agars and gels. We then move to looking at targeted therapeutics. The lab I am working in is interested in redox biology, and I am specifically working with a drug that inhibits a catalyst of Protein S-glutathionylation, basically inhibiting the addition of the small antioxidant glutathione to protein. We are analyzing RNA and protein from cells treated with this drug, and looking at its impacts on tumorigenic properties, such as migration.
In the world of research, a seven-week summer project is no time at all. You come in with lofty goals only to realize that every day a new hurdle is thrown at you. Patients don’t consent; the tumor cells don’t grow; your experiment to measure specific protein levels didn’t work and you have no explanation for why it didn’t. You learn that research is a slow process and there is nothing that can be done to make your cells grow faster or make that 48 hour time point come any sooner. But the most important lesson I learned this summer is that this whole project takes an immense amount of teamwork. From teams of nurses, oncologists, pulmonologists, pathologists and research coordinators working with the patients, to research technicians, graduate students and principle investigators working in the lab, the number of people involved in just obtaining and working with one sample is enormous. Cancer will not be cured by one person. It takes a team.