I have this little paragraph that I wrote in third grade in response to the question, What do you want to be when you grow up? I answered by saying, "When I grow up I want to be a scientist, live in the city, and ride my bicycle to my lab." By these standards, other than the fact that I walk to my lab instead of riding a bike, I have accomplished my dream.
Actually, to be precise, I wanted to be an astronomer because I thought the stars were so beautiful. But in high school I took physics and realized that this was the kind of science that I'd be studying in order to be an astronomer, not the hands-on things I enjoyed so much in my biology and chemistry classes. I went to Bates College in Maine for one semester, but the cold and distance from my family prompted me to transfer to St. Mary's College of Maryland, a small state school in southern Maryland, where my mom lives. St. Mary's had an honors program, which came with a full scholarship, and if I majored in biology I could graduate in four years, making up for the semester I lost in Maine.
Aversion to Jellyfish Stings Leads to Laboratory Science Work
St. Mary's is located in a beautiful part of Maryland, almost right at the convergence of the Potomac River and the Chesapeake Bay. Many of the biology students there took advantage of the unique estuarine environment and studied marine biology, but I didn't like getting stung by jellyfish. Although I ended up liking the molecular biology and biochemistry lab courses. By the end of my junior year, my biochemistry professor, David Cribbs, suggested that I participate in a summer program at the University of Maryland to get some real laboratory experience.
Taking his advice, I enrolled in the program and was placed in a neurobiology lab run by Dr. Moon Lee Shin. On the very first day of the program, with Dr. Shin away from the lab, one of the lab technicians asked me to help make mouse brain cultures. This was the starting point of my interest in the field of neurobiology. I found the experience so rewarding that I decided that I wanted to go to graduate school, the concept of which to me was wonderful -- you get paid (in those days, a little bit!) to study and learn how to use your hands and mind potentially to help cure people.
I wanted to find a graduate program in which I could focus on a combination of neuroscience and immunology. My number one choice was Yale, partly because of the work going on in the Shin lab on multiple sclerosis (MS) and partly because I spent some of my childhood in New Haven, where my father studied as a graduate student. I liked the environment, and they had an interdepartmental program that allowed me to do both neurobiology and immunology.
"Come Work for Me"
I started in the fall of 1991 and had a really hard time finding a thesis lab -- mainly because I loved every single lab I rotated through. Finally, I went to my neuroanatomy professor, Jeff Kocsis, and I said I didn't know what lab to choose. His answer was simple, "You can come work with me. We have some interesting molecular data about nerve injury and no one to follow up on it." I accepted his offer and never regretted it.
Dr. Kocsis not only encouraged me to be independent -- as an electrophysiologist with little background in molecular biology -- he forced me to be. He also strongly emphasized the wealth of the intellectual environment in the lab and at the rest of Yale and told me to make the most of it, which I eventually did, asking everyone in my lab and at neighboring labs for advice and reagents. This is something I try to stress to my own lab staff now -- share ideas and reagents with the people around us, since people sharing with me enabled me to get through grad school and postdoctoral training.
One of the things I liked best about the Kocsis lab was that much of the research being done was supported by the Paralyzed Veterans Association. On a regular basis, paralyzed vets would come through in wheelchairs -- the hallways of the labs were handicap-accessible -- and they would ask, "What are you doing and what does it have to do with my condition?" This was during the Persian Gulf War, and many of these people were near my age. It meant a lot to me that my work had some translational potential.
Signal Transduction in the Nervous System
As part of our research, we would injure rats' sciatic nerves -- the largest nerve in the body, running from the lower back to below the knee -- to better understand paralysis. When the injury is done to the nerve's periphery, the rats recovered. When the injury is done to the central nervous system (CNS), they didn't recover. This, of course, raised the question of what signals are different between the periphery and the CNS. I ended up finding signaling pathways that seemed to be important for nerve regrowth in the periphery. This solidified my interest in signal transduction in the nervous system.
I knew that I wanted to be a professor when I grew up, so it was obvious that I would go on to do a postdoctoral fellowship. In terms of where to do my postdoc, I knew I wanted to go to Boston, where I was born and where I still had some family and close friends. Because of my interest in signaling and how signaling transduction pathways affect outcomes that nerve cells experience, I looked at labs with signaling connections, particularly related to human disease. My motivation stemmed from how much I had enjoyed working with the veterans. I ended up in David Rowitch's developmental biology lab at the Dana-Farber Cancer Institute. David was working on a very interesting conundrum -- We know that children who have mutations that cause activity in a signaling pathway that is activated by a molecule called sonic hedgehog tend to get brain tumors, but we don't know how a sonic hedgehog molecule "talks" to the proliferation-regulating machinery inside cells.
My fellowship lasted almost seven years. After four years, I had a solid body of publications. I knew that I had a developmental biology program that I could develop on my own. David Rowitch and I agreed that if I stayed a little longer and managed to get a grant, I'd be able to expand my research program to include cancer. After being promoted to the instructor level, I applied for a grant from the Sontag Foundation, which supports young researchers doing brain tumor research. When I received the grant, I hired my own technician, Sarah Sjostrom, and, at the beginning of last year, I started looking at opportunities outside the Dana-Farber Cancer Institute.
I decided I wanted to work at a place where I could do good primary research and have an affiliation with a medical school or hospital that would allow me access to translational resources. My real expertise is in basic developmental neurobiology, but I wanted to make sure that I could apply my interests to medical research.
This Is the Place
In the fall of 2004, Eric Holland invited me to do a seminar here at Sloan-Kettering. I came down, did my talk, and went back home. They called me later and invited me to apply for a faculty position in the department of Cancer Biology and Genetics. I met with the members of the department and decided that, of all the places I'd visited, this was the place I wanted to go. Between Rockefeller University, Weill Cornell, and Memorial Sloan-Kettering, I have all the resources I could ever hope for. On my second visit, I was asked to meet with people on the clinical side at Memorial Hospital, and they were clearly interested in getting involved with research like mine. I knew then that I was in an environment where I'd have real collaborations with clinical and basic researchers, which to me is critical. As a result, my decision to accept their offer was not a difficult one.
When I arrived here, I was given everything that I needed to set up a good developmental biology research lab. I wanted to be able to follow my research wherever it took me, and it was clear that this was something I'd be encouraged to do here.
I staffed the lab quickly because I wanted people around to toss back and forth ideas and get moving on the projects I had in mind. I'm incrementally pushing the projects forward by making the tools and acquiring the necessary mice so that when someone comes in wanting to work on any particular project, they're ready to go.
So far it seems to have worked. My first fellow, Susana Parathath, found sufficient preliminary data and materials waiting for her so that she could get going easily on her work studying signaling in the developing brain. And another fellow will start this spring, studying a mouse model for medulloblastoma that I'm setting up here. We want to have medical fellows working in the lab, bringing their clinical perspectives. From almost the moment I started here, a number of people contacted me, from both the hospital and the research side. My hope is that the people in my lab will be motivated to succeed by the environment in the lab and by the availability of resources here. If this is the case, they will be able to generate results for the good of the lab, and, equally important, use their results as jumping-off points to develop their own ideas, which they can take away with them.
Research Goals
The goal of our laboratory is to use increased insight into neural precursor cell cycle regulation to better understand the etiology of brain tumors, develop mouse models for brain tumors, and identify novel targets for new treatment modalities, which may be tested using mouse models. The theme of our lab is modeling cell division in primary neural precursors in vitro and in mouse models for medulloblastoma in order to learn how cell cycle dysregulation contributes to human CNS disease, particularly cancer.
Medulloblastoma is the most common malignant solid childhood tumor. These tumors arise from precursor cells of the developing cerebellum, a brain region which undergoes rapid expansion after birth. Current treatments for these tumors include surgery, radiation, and chemotherapy, which cause lasting physical, cognitive, and psychological effects. Thus, development of more optimal treatments is of great importance. Links between neurodevelopmentally critical signaling pathways (such as those activated by sonic hedgehog, Notch, wnt, and insulin-like growth factor) and medulloblastoma formation or maintenance have been made. Our efforts include investigation of how such pathways interact with each other and with the cell cycle regulatory machinery; characterization of specific pathway targets; functional analysis of the pathways' effectors; and genetic manipulation of these pathways and their targets in mice to better understand brain development, cancer, and CNS pathologies.
I  NY
I love New York so much -- surprisingly, I don't miss Boston at all! Harvard and Boston have many great things going on, but I have yet to find anything missing here -- including terrific cycling and running routes. Living in New York is like an adventure every day, and that sense of excitement permeates every part of my life, including and especially my research. I have high hopes and plans for my work here and I feel confident that with the resources available, I will be able to achieve those goals.
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