The Neurosurgical Oncology Laboratory and the Brain Tumor Bank of the Department of Neurosurgery, Brigham and Women’s Hospital, work hand-in-hand to support the development of novel therapies for controlling brain tumor growth. Many of these tumors originate in the glial cells (cells that surround and protect the nerves), while others develop in the meninges (the membranes that surround the brain and spinal cord). “The prognosis for patients with glioblastoma,” for example, is very poor ranging “between 12 and 18 months from diagnosis,” according to Dr. Carroll, “even when patients are treated with adjuvant chemotherapy or radiotherapy.” A number of agents have been demonstrated to have a tumoricidal (cell killing) effect in laboratory cell cultures, but the problem lies in finding an optimal method for delivering the cytotoxic agent to the tumor site, where it will do the most good without harming the patient. The current thrust of the research Dr. Carroll oversees in her capacity as Associate Director of the Neurosurgical Oncology Laboratory and Director of the Brain Tumor Bank is the development of new and improved drug delivery systems.
Dr. Carroll is a graduate of Pitzer College, Claremont, CA. She received a Master’s degree and Ph.D. in neuroscience from the Massachusetts Institute of Technology. After completing her dissertation at MIT, she came to the Brigham and Women’s Hospital and fulfilled a two-year fellowship in endocrinology. In 1992 she switched disciplines and was named Associate Director of the Neurosurgical Oncology Laboratory under the direction of Dr. Peter Black, Chief of the Department of Neurosurgery. Dr. Carroll has been with the Neurosurgery Department ever since. In 2002, Dr. Carroll was promoted to Assistant Professor of Neurosurgery of the Harvard Medical School and Brigham and Women’s Hospital.
Dr. Carroll has dual responsibilities as Associate Director of the Neurosurgical Oncology Laboratory and as Director of the Brain Tumor Bank, which was established in 1986 by Dr. Black. The Neurosurgical Oncology Laboratory is conducting research in three principal areas: microparticle delivery systems; therapeutic stem cell research; and animal model development for meningioma research.
Microparticle delivery systems are placed into the patient’s surgical cavity at the time of tumor resection. These polymeric particles release antiangiogenic and antiproliferative agents at the tumor site. This research is currently being conducted in animal models.
The use of stem cells as a therapeutic delivery vehicle for the treatment of brain tumors is being explored. The Neurosurgical Oncology Laboratory has shown that neural stem cells have the ability to migrate to brain tumors including the microsatellites that migrate away from the main tumor mass. The goal of this research is to identify a source of stem cells that can be used safely in patients and then transduce these cells with an antitumor agent that is released when it reaches the tumor target. The laboratory is currently seeking funding for conducting stem cell studies in humans.
Research is also being conducted on meningiomas, a more benign tumor that nonetheless is capable of invading into the normal brain. This work was made possible through a large philanthropic grant made to the Department of Neurosurgery by the Brain Science Foundation. The emphasis of this research is to develop a good animal model for studying meningiomas, since none currently exists. The laboratory is also investigating the use of genomic techniques, such as SNP analysis, to better define the molecular mechanism responsible for the proliferation of these brain tumors. One of the genes thought to be responsible is called NF2. The current animal model only produces tumors in about 30 percent of animals and therefore a better model is needed.
Dr. Carroll’s laboratory is currently staffed with five postdoctoral fellows in addition to individuals providing technical support. Dr. Carroll is open to a wide range of applicants for positions in her laboratory. “It’s good to have a strong basic science background, but I think personality and motivation are critical.” The laboratory also recruits and trains physicians, including a number of neurosurgeons who have never done research before. “The most important thing is compatibility, someone you think you can work with. That’s critical.”
Among the laboratory’s many collaborations, Dr. Carroll highlights projects with the Harvard-Partners Genetic Core, which has been helpful in developing the SNP analysis; investigators from the Children’s Hospital Medical Center including Dr. Marcelle Maclluf a biomedical engineer at Technion Hospital in Haifa, Israel. Dr. Marco Giovannini, an expert on the NF2 gene mutation, is also working with Dr. Carroll’s group to develop new methods in SNP analysis to better delineate the NF2 gene.
Dr. Aster has indicated that there is a tremendous added value to being a member of a department with a very strong commitment to research that is located within an institution providing world-class care to patients. The department of pathology at Brigham and Women’s Hospital has always had a strong research focus, first fostered by Dr. Cotran and subsequently maintained by his successor, Dr. Michael Gimbrone. This, in turn, has attracted many outstanding residents and fellows with strong research interests of their own. Among the several talented trainees who have passed through Dr. Aster’s laboratory are Andrew Weng, M.D., Ph.D., (now at the British Columbia Cancer Agency) and Chris French, M.D. Both of these individuals made innovative and important contributions to cancer research during their time at Brigham and Women’s Hospital.
Long term, the hope of the Neurosurgical Oncology Laboratory is to be able treat patients with brain tumors using stem cells as a therapeutic delivery vehicle. In other words, at the time of the first tumor resection, a bone marrow sample would be isolated, frozen, and kept in the bone marrow bank. In the case of glioblastomas, for example, which mainly recur within 9 to 12 months, just before the second surgical resection, the stem cells would be thawed, cultured, analyzed for overexpressed growth factors, and transduced with the appropriate therapeutic gene.
The Neurosurgical Oncology Laboratory is funded from a variety of sources including private donations, a grant from the Harvard Stem Cell Institute. Binational Science Foundation, which is a US-Israeli grant that supports the micropolymer research, and the National Institutes of Health.
Menon LG, Pratt J. Yang HW, Black PM, Sorensen GA, Carroll RS. Imaging of Human Mesenchymal Stromal Cells: Homing to Human Brain Tumors. Journal of Neurooncology, . 2012 Apr;107(2):257-67. Epub 2011 Nov 12.
Yang HW, Kim TM, Song SS, Shrinath N, Park R, Kalamarides M, Park PJ, Black PM, Carroll RS, Johnson MD. Alternative splicing of CHEK2 and co-Deletion with NF2 promote chromosomal instability in meningioma. Neoplasia, 2012 Jan;14(1):20-8. PMID: 22355270
Thompson IR, Ciccone NA, Xu S, Zaytseva S, Carroll RS, Kaiser UB. GnRH pulse frequency-dependent stimulation of FSHβ transcription is mediated via activation of PKA and CREB. Mol Endocrinol. 2013 Apr;27 (4):606-18. doi:10.1210/me.2012-1281. Epub 2013 Feb 7. PubMed PMID: 23393127; PubMed Central PMCID: PMC3607701.