My name is David Quigley, I am an assistant adjunct Professor here at UCSF where I have been for more than a decade. I work on cancer genetics, primarily prostate cancer but I have worked in the past on skin and breast cancer quite extensively.

I sometimes describe myself as a translational geneticist. There’s two words there, and geneticist might make a little more sense to someone who’s not familiar with our way of describing ourselves, because that means that I’m interested in genetics, I’m interested in how changes in the DNA instructions inside of cells, create cells, and how they influence how cells behave. And particularly, since I’m interested in cancer biology, how when those information in the cell are changed or are broken in some way, what are the consequences of that. So that’s the genetics, being concerned fundamentally with how traits, how features of people or animals are passed from one generation to the next. Translational means that I’m very interested in trying to understand what would affect patients and patient care and people with disease.

So part of what we try to understand is whose going to benefit from drugs. Specifically, when it comes to my work and understanding the BRCA family of genes, the drugs we are most interested in are the so-called parp inhibitors. Drugs like Olaparib. We try to understand which cells will be sensitive to those drug, in an effort to extrapolate, then to say, if we identify patients whose cells behave like the ones that we understand in the dish, then we can hypothesize that they are also likely to benefit. We run a study where patients consent to have biopsy samples studied by scientists, what we can do then is take those biopsies and then extract out the DNA from the tumors and then ask: “What mutations were present in this tumor?” Once we see a pattern over and over again we can, on the one hand, correlate the sensitivity of somebody to a drug with the presence of a particular kind of mutation, and we can also look at the genome of the cells as well. One of the things we look at is, when tumor cells can’t do the kind of repair that the BRCA2 and BRCA1 genes are responsible for, it kind of leaves a trail of wreckage in the genome over time, because of the inability to repair the cell’s DNA, it leaves what we call a scar, a genomic scar. One of the things we’ve studied is, is that scar present in patients who have different kinds of mutations, because then instead of modeling the cells in a dish, what we can do is, use the tumor itself as a readout for whether that particular mutation resulted in the same kind of vulnerability that we’re looking for.

You never know with science whether the question youre posing has a clear answer or not. As I started out as a software engineer, that’s a really wonderful discipline, but it’s a fundamentally different kind of discipline because your building things entirely out of tools that you make yourself. We’re exploring territory that we didn’t design. So the sheer challenge of what we’re doing is always humbling but keeps things interesting.