BRI Cancer Research Center

Focus

Dr. Mark Johnson’s laboratory is focused on a particular class of tumors called gliomas. There are 50,000 new cases of gliomas in the United States each year. These tumors arise within the brain and, while they do not spread to other parts of the body, they tend to spread widely within the brain. High-grade malignant tumors have an especially short survival of just over one year. Low-grade tumors have median survivals between five and ten years, but also are not usually curable. Present treatments typically involve surgical resection followed by radiation and chemotherapy. Dr. Johnson’s research is focused on finding new and better ways to treat this important class of cancer.

Background

A native of Memphis, Tennessee, Dr. Johnson attended Phillips Exeter Academy. He attained an undergraduate degree at Amherst  College, followed by an M.D.-Ph.D. in neurobiology at Harvard Medical School. He completed his internship and residency in urological surgery at University of Washington, Seattle. Then after a postdoctoral fellowship in Seattle and further postdoctoral work at the Oregon Health and Sciences University, he returned to Boston and Brigham and Women’s Hospital, where he is a clinical neurosurgeon and the director of his own research laboratory.

Research

Dr. Johnson approaches gliomas from two different perspectives. He uses microarray platforms to discover changes in the structure and expression of glioma genes. He has developed new approaches to combine these genome-wide types of analysis with clinical data, including patient survival and outcome. These studies are used to determine what kind of treatments will be most effective. The second approach seeks to discover the basis for tumor development by focusing on the cellular origins of brain tumors.

Recent studies suggest that gliomas arise from a stem-cell -like population within the brain. Dr. Johnson and his colleagues are working to define and characterize the stem cell populations that give rise to various kinds of brain tumors. He feels that by understanding the cell of origin better we will come up with new ways to target this cell, which must be eliminated if gliomas are to be cured. Dr. Johnson and colleagues have identified the transcription factor beta-catenin, which participates in the Wnt signaling pathway, as being an important player in glioblastoma, albeit one with a complex role. Of note, the Wnt signaling pathway has been shown to be important in the renewal of normal and some other kinds of malignant stem cells, making it a promising candidate for involvement in the self-renewal of glioma stem cells. Dr. Johnson’s laboratory is also performing studies that seek to understand the basis for glioma resistance to radiation and chemotherapy, as well as the propensity of this tumor to spread widely from the primary tumor site into adjacent normal brain tissue.

Laboratory

Dr. Johnson’s laboratory currently has two postdoctoral fellows, a Master’s degree candidate, and a technician. Additionally, college and medical students are offered a limited number of internship positions.

Collaborations

Dr. Johnson works closely with the laboratory run by Dr. Peter Black, chief of the Division of Neurosurgery, and Dr. Black's associate, Rona Carroll.  Dr. Johnson also participates in banking tumor tissue in the extensive Brain Tumor Bank.  Additionally, he has widespread collaborations both within and outside of Boston.

Funding

Dr. Johnson’s laboratory is funded by a combination of Federal support from the National Institutes of Health, as well as private foundation support, including a distinguished scientist award.

Importance of Being at the Brigham

Brigham and Women’s Hospital is one of the premier institutions for the treatment of brain tumors. “For many years,” Dr. Johnson explains, “Dr. Peter Black, has led that effort. The large population of neurosurgical patients, our extensive in-house tumor bank, and the large number and wide variety of investigators in neuroscience, pathology, oncology, and epidemiology make the Brigham an ideal place for collaboration and conduct of neurosurgical research.”

Future

Dr. Johnson offers “If we are able to identify the factors that regulate tumor self-renewal and differentiation, I think this will usher in a period of new therapies and a fresh approach to treating these tumors. Our laboratory is also at the forefront of identifying pathways that control tumor cell migration. We have already found potential candidate molecules, which may affect migration of tumor cells. We look forward over the next few years to developing more molecules capable of taming these tumors cells. We also look forward to developing stem cell therapy for brain tumors in collaboration with Dr. Black’s laboratory.”

Selected References

Liu F, Park PJ, Lai W, Maher E, Chakravarti A, Durso L, Jiang X, Yu Y, Brosius A, Thomas M, Chin L, Brennan C, DePinho RA, Kohane I, Carroll RS, Black PM, Johnson MD. A genome-wide screen reveals functional gene clusters in the cancer genome and identifies EphA2 as a mitogen in glioblastoma. Cancer Res. 2006;66:10815-10823.

Yu Y, Jiang X, Schoch BS, Carroll RS, Black PM, Johnson MD. Aberrant splicing of cyclin-dependent kinase-associated protein phosphatase KAP increases proliferation and migration in glioblastoma. Cancer Res. 2007;67:130-138.

This page was last modified on 7/7/2007