Portal de Periódicos da CAPES

Jeannie T. Lee

2008; Elsevier BV; Volume: 18; Issue: 20 Linguagem: Inglês

10.1016/j.cub.2008.07.087

1879-0445

Jeannie T. Lee,

Nutrition, Genetics, and Disease

Jeannie T. Lee is an Investigator of the Howard Hughes Medical Institute and Professor of Genetics (and Pathology) at Harvard Medical School and the Massachusetts General Hospital. She was an undergraduate at Harvard University where she majored in Biochemistry and Molecular Biology, and worked with Nancy Kleckner on the control of Tn10 transposition by antisense RNA. She then obtained M.D.-Ph.D degrees from the University of Pennsylvania School of Medicine, where she became interested in epigenetic regulation of human disease while a dissertation student with Robert L. Nussbaum. Afterwards, she trained briefly in Clinical Pathology at the Massachusetts General Hospital, before joining Rudolf Jaenisch at the Whitehead Institute as a postdoctoral fellow. Since she became independent in 1997, her lab's interests have included X-inactivation, imprinting, the emerging link between noncoding RNA and chromatin control, and the evolutionary history of sex chromosomes and dosage compensation. She is also passionately interested in the interaction between environment and genome and imagines pursuing this during the next stage of her career. She has received the Basil O'Connor Scholar Award from the March of Dimes and the Pew Scholars Award from the Pew Foundation. Currently, she serves on NIH study section (grant review panel), is an Associate Editor for the Public Library of Science (Genetics), and is co-organizing the next Gordon Conference in Epigenetics. What turned you onto science? I was sure that I would become a physician, but then I took a major in physics and chemistry in college. In my sophomore year, I had an epiphany: after a lecture course by Mark Ptashe, Tom Maniatis, and Doug Melton, I realized I ought to be in molecular biology. After one semester in the Kleckner lab, however, Nancy told me I had to work harder and think better. I tried. A career in basic science was not an obvious substitute for medicine. But soon I learned that experimental discovery is one of the most rewarding experiences in life. Twenty years later, I am a basic scientist — still working on noncoding RNA — and still getting that high out of science. What attracted you to X-inactivation? It was easy to fall in love with this problem — everything about it is like a great detective story. In Bob Nussbaum's lab as a PhD student, I was already well aware of the mystery, but not until I heard the XIST story from Hunt Willard's group did I think seriously about working on it. XIST encodes an untranslated RNA that shows the reverse pattern of expression from all other X-linked genes in female mammals – The RNA is expressed only from the ‘inactive’ X and spreads all over that chromosome to form an RNA blanket. An RNA that sticks to a chromosome and regulates its gene expression was just too interesting to pass up! Rudolf's lab was a great place to test the ideas in mice, so that is where I got my start in X-inactivation. In Rudolf's lab, I transplanted a 450 kilobase region of the X-inactivation center to an autosome and found that it can serve as a silencing center at the ectopic location. This discovery gave me the start I needed to identify new regulatory elements in my own lab. The transgene analysis paved the way for the discovery of Tsix and Xite. If you could do it all over again, would you choose the same career path? This is the best job in the world. Sometimes (only sometimes) I think I might skip medical school next time around. I was not a natural medical student, but I learned many things that are put into daily practice in a non-obvious way. For example, mouse embryology is much easier when one has been taught human anatomy and physiology. Applying concepts in X-inactivation and epigenetics to human health also comes much more easily. Although my lab has focused exclusively on basic science up to this point, I have not abandoned plans for medicine at all. My plan is to link epigenetics to human disease during the next stage of my career. I have recently steered part of my lab in that direction with work on human embryonic stem cells which, as we have come to learn, show aberrant epigenetic regulation. There is a lot to learn from this much needed human model. What do you enjoy most about science? The challenge, the discovery, and the people. In this profession, one meets some of the brightest (and most eccentric) minds on Earth. Although I dislike airports and flying, I do enjoy the chance to see different cultures, experience science as it is done in other countries, and taste great food (I always enjoy myself once I am there). Through science, one has the chance to make a lasting positive contribution to our society and planet. Are there any disappointments in science? For me, one of the biggest attractions to science is that it is inherently value-free. There is one truth that cannot be changed by culture, history, and politics. But I no longer think that science is devoid of politics. Science itself is objective, but the practice of it is about people, personalities, and perceptions of what is important. We see this in the way grants are awarded, papers published, and policies established by the government. I see great ideas that are not given a chance at being tested because of diminishing resources; or great ideas not finding an appropriate place in the literature because of a general unwillingness to take risks on very imaginative thinking. Perhaps there is no way around this, especially with the current crisis in grant funding. Both junior and seasoned investigators spend a lot of time writing grants to keep their laboratories alive when their time would be more productively spent on experiments. Any career advice for someone just starting their own lab? Stay at the bench for as long as possible, because it is more rewarding to do experiments than to exercise your administrative skills in the office. Nowadays, I am more coach, cheerleader, and psychologist than experimentalist — sadly. The people you hire are your greatest assets — choose and treat them well. Hire people with complementary skills and always try to keep a balance of talent and personalities in the lab. Over the years, I have come to value talent, work ethic, honesty, and collaborative spirit equally. Are there gender differences in science? As someone who makes a living out of studying male and female differences, you might think that I am hardwired to think so! But I am not a big proponent of the idea that men and women inherently do science differently. Whatever difference there is, I am certain that there are many more differences among individuals and cultures than between the sexes. This I see in practice everyday. From what I can see in my own lab, there is not a significant ‘delta’ in work hours, talent, and commitment. What emerging problems interest you most? There are so many problems I would work on now. If I were a student thinking about science, I might focus on environmental issues, energy, neurobiology, or cognitive science. I also think that the areas of genome–environment interactions and environmental toxicology (branches of epigenetics) will blossom in the coming years. What would you like to see solved in the next 10 years? An end to global warming and pollution. I would also like to see better land stewardship and conservation. Do you think I'm unrealistic? What advice would you give a student thinking about a career in academic science? You must love it — everything about it, from writing and speaking to thinking and doing. As with anything else in life, it is easier to love something when you are good at it. So find a problem that suits your talent and personal goals. Expect no immediate rewards (money, fame, prizes). If you are passionate about science, you will survive grant writing, paper rejections, and the long road to tenure. A life in science is one of the best there is.