FEATURED INVESTIGATOR
MARK JOHNSON, MD, PHD

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 directs the Molecular and Cellular Brain Tumor Laboratory in the Department of Neurosurgery at Brigham and Women’s Hospital and Harvard Medical School.  Dr. Johnson’s laboratory is focused primarily on the genomics and cellular biology of glioblastoma (GBM) and meningioma.  These studies have included analyses of genome-scale mRNA, microRNA, array CGH, SNP and high throughput deep sequencing data sets. Once genes of interest are identified, they investigate their roles in brain tumor biology using human brain tumor cell lines, primary tumor cells from surgical specimens, in vitro assays, in vivo mouse models and clinical data set analyses. Dr. Johnson and his colleagues have focused on mechanisms of tumor growth, invasion, differentiation, progression and resistance, and are working to identify new therapeutic agents and treatment approaches.

 

In general, The Johnson Laboratory uses genomics and clinical annotations as a starting point for discovery and subsequent molecular and cellular investigations. In collaboration with a bioinformaticist, Dr. Peter Park, they have analyzed a variety of genome-scale platforms, developed new analytical methods, and integrated multiple genomic data sets to gain new insights into the biology of glioblastoma, meningioma and brain metastases.

 

Dr. Johnson’s laboratory is also using genome-scale approaches to discover new invasion-related molecular pathways in glioblastoma, and they are working to identify new drugs to block glioblastoma cell invasion. In addition, Dr. Johnson is investigating the role that microRNAs play in glioblastoma aggressiveness. Dr. Johnson and his colleagues recently used microRNA expression profiles from The Cancer Genome Atlas (TCGA) to identify five clinically and genetically distinct subclasses of glioblastoma (including a novel subclass), each of which relates to a different neural precursor cell type (Kim TM et al, 2011). They showed that a subset of microRNAs contributes to glioblastoma subclass identity by regulating glioblastoma cancer stem cell differentiation. They have also identified several microRNAs that promote glioblastoma aggressiveness.

 

In addition to the glioblastoma studies described above, Dr. Johnson and his colleagues are using genomics to investigate mechanisms of tumor progression in meningioma, the most common type of primary intracranial brain tumor. As part of this effort, they recently identified a molecular mechanism that helps to explain the genomic instability observed in meningiomas with loss chromosome 22q. They are also working to understand why meningiomas are resistant to most types of chemotherapy.

 

Dr. Johnson’s laboratory also has a primary interest in normal pressure hydrocephalus, a disorder that usually presents during adulthood and is characterized by dementia, incontinence and gait difficulty. The laboratory uses genomic and molecular approaches to try to understand the causes and develop better treatments for this disorder.

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.

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.

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.

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
  • Kim TM, Xi R, Luquette LJ, Park RW, Johnson MD, Park PJ. Functional genomic analysis of chromosomal aberrations in a compendium of 8000 cancer genomes.  Genome Res. 2013 Feb;23(2):217-27. doi: 10.1101/gr.140301.112. Epub 2012 Nov 6. PMID:23132910

 

  • Jiang X, Xing H, Kim TM, Jung Y, Huang W, Yang HW, Song S, Park PJ, Carroll RS, Johnson MD.  Numb regulates glioma stem cell fate and growth by altering epidermal growth factor receptor and Skp1-Cullin-F-box ubiquitin ligase activity.  Stem Cells. 2012 Jul;30(7):1313-26. doi: 10.1002/stem.1120. PMID:22553175

 

  • 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 codeletion with NF2 promote chromosomal instability in meningioma. Neoplasia. 2012 Jan;14(1):20-8. PMID:22355270
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