What does your lab study?
TANTIN: The unifying theme is gene regulation by sequence-specific DNA binding transcription factors. We seek to understand how transcription factors receive signals, how they regulate their downstream targets, and the biological consequences. Because some of the transcription factors we are studying are multifaceted, we wind up studying an array of different biological systems and disease states, for example lymphocyte development and function, early embryonic development, stem cells, and cancer - both solid and hematological tumors.
Would you classify your lab research as basic or translational?
TANTIN: I would classify it as basic research. Even if an activity we are studying controls a disease state, for example the transcription factor Oct1 and the maintenance of a leukemia phenotype, our goal is to understand the basic molecular mechanisms that underlie control of that phenotype. As our research progresses and these projects reach a threshold of understanding, we start thinking about application and clinical translation. For example, we now know that Oct1 is overexpressed at the protein level (but not message level) in several forms of “cancer stem cells”. That information raises the question of whether or not Oct1 could be used as a prognostic marker in certain forms of malignancy.
Why is basic research still important and why do you conduct basic research?
TANTIN: This is an important question. As I said above, we only start thinking about translation when our basic projects have reached a certain advanced stage of maturity. Not doing so would result in a train wreck. Translation is inefficient enough. Conducting it without basic understanding makes the odds of return on that investment unfavorable. You can think of it like a pyramid with basic research as the base. You would never invest most of the resources in building the top of the pyramid without supporting the base. Doing so would result in an “upside-down pyramid” and any 4 year-old can tell you what happens to a structure like that. Now as far as your second question goes, I just enjoy the discovery component, by which I mean finding out how things work at a basic molecular level.
When did you first start your present line of experimentation?
TANTIN: That is a hard one to pin down. I began work on the family of transcription factors we still study in 1998, as a postdoc in Phil Sharp’s lab at MIT. Since then I have studied different members, but the focus on that transcription factor family is still there. In 2004 I discovered that loss of one the factors I mentioned before, Oct1, did not have the effects we were expecting. Cells grew normally, they looked normal in a light microscope, but they were sensitive to different forms of stress like ionizing radiation for example. I like to highlight that date as a point of departure, as well as 2009, when my lab showed that Oct1 did not really activate target genes very well, but instead was very good at insulating them from repression. Subsequently in 2011 we identified the mechanism. A lot of our current efforts are devoted to understanding the biological implications and whether other members of this family use similar mechanisms.