Associate Professor Francis Szele
Group Leader in Developmental Biology
When did you first get interested in the brain?
I took an abnormal psychology class as an undergraduate in 1983 that explained the dopamine hypothesis of schizophrenia. I thought it was fascinating that a single molecule could have such a profound and devastating effect. It also made me realise that the brain is the nexus of the human condition and if you are interested in humans the brain is a pretty good place to start. I also did my first stint during my college years - actually in Montpellier France, weirdly enough in the Privat lab which was studying a neurogenic zone which at the time was called the Subependymal layer, I guess it was my destiny to study this layer of stem cells.
Who has inspired you during your career?
Marie-Francoise Chesselet and Connie Cepko. Marie-Francoise was my PhD adviser at the University of Pennsylvania. I heard her give a talk on the chemical neuroanatomy of the basal ganglia and decided then and there to be her student. She has a great passion for science and excellence and is very broad in her thinking. MFC gave me lots of freedom to bring adult subventricular zone (SVZ) neurogenesis into her lab. Connie was my postdoc adviser at Harvard and is one of the smartest people I know. She was the youngest woman to get tenure at Harvard Medical School and had the courage and foresight to use tools from virology in developmental neurobiology. She is one of the most creative scientists I have met having invented DNA barcoded lineage analysis which now has been co-opted in many sub disciplines.
What has been the most important paper in your area in the last 12 months?
Jonas Frisen has published a series of articles over the past several years using radioactive carbon (from nuclear bomb tests) for retrospective human cell birthdating. He has claimed that the human subventricular zone contains proliferative cells and that striatal calretinin+ CR+ interneurons are generated throughout life. If this is true, it will re-write the adult neurogenesis field as in all other mammals, neurons made in the SVZ migrate to the olfactory bulbs. In humans the striatum is far more functionally important than the OB and a good target for regenerative medicine via stimulation of endogenous SVZ stem cells, an idea my group is working on with the new company OxStem Neuro. It is also important because we recently published that the number of CR+ neurons is diminished in autism.
What is the next exciting breakthrough in your field going to be?
I have become very interested in what keeps the SVZ from generating even more cancers than already occurs. There are strong homeostatic mechanisms that promote and that limit SVZ-derived gliomagenesis. Ian Tomlinson's group and we have published a paper describing the knock-in of a human Idh1R132H mutation into the SVZ, generating the first in vivo and in vitro model of this common brain cancer. One of my hopes is to use this new mouse to understand what mechanisms limit cancer stem cells.
What do you do outside the lab?
Have conversations with my wife Jane, and with friends and work in the garden and ride horses in the beautiful countryside near our village of Stonesfield.
What’s your favourite music?
As far as I am concerned there is no modern music before and since Jack White. I love everything he has done. If you have never heard his work, you could start with this: