Dr. David Louis, Pathologist-in-Chief at Massachusetts General Hospital (MGH) and Benjamin Castleman Professor of Pathology at Harvard Medical School, is an internationally recognized expert in brain tumor pathology and molecular genetics. With over 20 years of experience in the application of molecular diagnostics to glioma classification, he along with Dr. Gregory Cairncross (University of Calgary), were the first to demonstrate the clinical significance of 1p/19q loss in oligodendrogliomas. He has been collaborating with Dr. Bradley Bernstein in glioblastoma epigenetics for the past two years. In addition to this prestigious work, Dr. Louis was recently named one of the two (initial) grant recipients for the National Brain Tumor Society Oligodendroglioma Research Fund, and will be named as the 2013 Feldman Founders award recipient at our upcoming Annual Meeting.
In anticipation of accepting this award, Dr. Louis graciously agreed to answer a few questions about his contributions to the field of brain tumor research, including updates on his current oligodendroglioma research and its ability to leverage his earlier discoveries in glioblastoma multiforme (GBM):
Can you explain what role a Pathologist plays in the research and treatment spectrum? Pathologists guide clinical care by providing laboratory-based information to the treating doctors. When a treating doctor takes a biopsy, blood sample, or throat swab, a pathologist analyzes the samples and those results are then used to guide treatment. For a brain tumor patient, pathologists provide the diagnosis of the particular type of tumor, perform any molecular evaluations on the tumor, and then do all of the blood tests during the course of treatment.
In research, pathologists play many roles. Many of us are scientists who run our own research laboratories, while others provide support services to scientists. For example, if a scientist is studying a particular type of tumor, a pathologist must analyze the tumor to let the scientist know if it is the intended tumor type.
Why did you choose to focus on brain tumors in you personal studies? I was always interested in the brain and initially intended to be a neurologist. But, it must be partly genetic, since my father and brother are neurologists! In my last year of medical school, I spent two months at Memorial Sloan-Kettering Cancer Center and that experience made me particularly interested in the oncological aspects of neurology. Once I switched to training in neuropathology, I began working in brain tumor research at a molecular level.
One of your earliest grants came from the (former) Brain Tumor Society*, how did this grant help jumpstart your career? The grant that I had received from the Brain Tumor Society enabled me to focus on a particular area (i.e. oligodendrogliomas), which helped provide the data that led to the important findings related to chromosome 1p and 19qdeficiencies, and provided a significant impact on the management of oligodendroglioma patients. These assessments are now a routine part of clinical care of oligodendroglioma patients around the world.
How has the field changed since then? Our ability to interrogate the genetic basis of human tumors has expanded tremendously over the past 10 years and we can do analyses today to an extent that was almost unimaginable in the 1990s.
Can you discuss how your earlier findings in glioblastoma multiforme (GBM) have informed your current work in oligodendrogliomas? I have worked with Drs. Mario Suva and Brad Bernstein to study GBM at the “epigenetic” level (i.e., the level at which genes are controlled). Through these studies, Dr. Suva has clarified a set of control factors (transcription factors) that seem to be responsible for making a GBM stem cell have its particularly aggressive features. We are now using epigenetics to study oligodendrogliomas.
What is your hope for your current oligodendroglioma work**? How do you see it moving the field forward toward better solutions for patients? The eventual behavior of tumor cells relates to how their proteins act. Protein activity is increased when genes are activated. Epigenetics is a field that studies how genes are activated and inactivated. Therefore, the study of the epigenetic landscape of oligodendrogliomas will give us knowledge about what changes control the molecules which make cells cancerous. From a treatment point of view, it is exciting that epigenetic changes may be more straightforward to manipulate for therapeutic ends than are genetic mutations.
* The Brain Tumor Society was one of the two legacy organizations that later merged to become the National Brain Tumor Society
**Dr. Louis’ current project for the National Brain Tumor Society’s Oligodendroglioma Research Fund:
Mapping the Epigenomic Landscape of Oligodendroglioma to Elucidate Tumor Growth and Chemosensitivity
Dr. Louis and his team will seek to identify the elements that drive the growth of oligodendrogliomas by applying next-generation sequencing tools and experiments. Dr. Louis’ work is designed to lead to discoveries of specific molecular targets, which subsequent studies would examine for potential therapeutic approaches.