Other Appointments/Positions

Vice Chair, Translational Programs, Department of Pathology and Laboratory Medicine

Director, Cancer Tissue and Pathology Core, Winship Cancer Institute

Co-Director, Pathology Residency Training Program, Emory University School of Medicine

Director, Neuropathology Division, Emory University School of Medicine

Director, Neuropathology Fellowship, Emory University School of Medicine

Neuropathology Attending, Emory Healthcare Hospitals

Neuropathology Attending, Children's Healthcare of Atlanta Hospitals

Pathology Division(s):
Anatomic Pathology
Experimental Pathology

Email Address:
dbrat@emory.edu

Education:

MD   Mayo Medical School, Rochester MN, 1987 - 1994

PhD   Mayo Graduate School, Rochester MN, 1987 - 1994

Residency   Anatomic Pathology, Johns Hopkins Hospital, Baltimore, MD, 1994 - 1997

Fellowship   Neuropathology, Johns Hopkins Hospital, Baltimore, MD, 1997 - 1999

Research Interests:

- Mechanisms Underlying Glioblastoma Progression
We investigate mechanisms of progression to glioblastoma (GBM), the highest grade astrocytoma, including genetics, hypoxia, and angiogenesis. Progression is characterized by tumor necrosis, severe hypoxia and microvascular hyperplasia, a type of angiogenesis. We propose that vaso-occlusion and intravascular thrombosis within a high grade glioma results in hypoxia, necrosis and hypoxia-induced microvascular hyperplasia in the tumor periphery, leading to neoplastic expansion outward. Since the pro-thrombotic protein tissue factor is upregulated in gliomas, we investigate mechanisms of increased expression and pro-coagulant effects.

- In Silico Brain Tumor Research
We initiated an In Silico Center for Brain Tumor Research to investigate the molecular correlates of pathologic, radiologic and clinical features of gliomas using pre-existing databases, including as TCGA and Rembrandt. Using datasets and image analysis algorithms, we study whether elements of the tumor micro-environment, such as tumor necrosis, angiogenesis, inflammatory infiltrates and thrombosis, may correlate with gene expression subtypes in TCGA gliomas. We also have demonstrated the clinical relevance of TCGA subclasses within the lower grade gliomas using the Rembrandt dataset.

- Regulators of Asymmetric Cellular Division in Glioblastoma Stem Cells
We study mechanisms that confer specialized biologic properties to glioma stem cells (GSC) in GBM. The Drosophila brain tumor (brat) gene normally regulates asymmetric cellular division and neural progenitor differentiation in the CNS of flies and, when mutated, leads to a massive brain containing only neuroblastic cells with tumor-like properties. We study the human homolog of Drosophila brat, Trim3, for its role in regulating asymmetric cell division and stem-like properties in GSCs. Trim3 may elicit its effects is through repression of c-Myc.

Clinical Focus:

My clinical interest is diagnostic neuropathologist with a focus on brain tumors. Together with my colleagues in the Neuropathology Division, I am responsible for the pathlogic diagnosis of brain lesions from patients seen at Emory Healthcare Hospitals and Children's Healthcare of Atlanta Hospitals. I also direct the Neuropathology Fellowship and co-direct the Pathology residency, with an emphasis on recruitment and career development.

Honors / Awards:

Woodruff Health Sciences Center Leadership Academy, 2010

Scientific Advisory Board, Southeastern Brain Tumor Foundation, 2009-

Georgia Cancer Coalition Distinguished Cancer Scholar, 2009

Lower Grade Gliomas (Chair) and Glioblastoma Working Groups, The Cancer Genome Atlas (TCGA) Project, National Cancer Institute (NCI), 2008-

Scientific Advisory Committee, Goldhirsh Foundation, 2008-

Neuropathology Committee (Chair), College of American Pathologists, 2006-present

Advisory Committee, World Health Organization Classification of Brain Tumors, 2006

Lucien J. Rubinstein Award, American Association of Neuropathologists, 2004

Pathology Committee, Radiation Therapy Oncology Group, 2000-present

Editorial Boards: Neuro-oncology, Journal of Neuropathology and Experimental Neurology, Brain Pathology, Neurosurgery, Archives of Pathology and Laboratory Medicine, Neurosurgery, American Journal of Clinical Pathology, 2000-present

Benjamin Castleman Award, United States and Canadian Academy of Pathology, 2000

Matthew T. Moore Award, American Association of Neuropathologists, 1997

Alpha Omega Alpha, 1996

Phi Beta Kappa, 1987

Specialty Boards:

1997 Diplomate, Anatomic Pathology, American Board of Pathology

1999 Diplomate, Neuropathology, American Board of Pathology

Selected Publications:

Published and Accepted Research Articles -

Cooper LA, Gutman DA, Chisolm C, Appin C, Kong J, Rong Y, Kurc T, Van Meir EG, Saltz JH, Moreno CS, Brat DJ. (2012) The tumor microenvironment strongly impacts master transcriptional regulators and gene expression class of glioblastoma Am J Pathol 180:2108-19.

Munson JM, Fried L, Rowson SA, Bonner MY, Karumbaiah L, Diaz D, Courtneidge SA, Knaus U, Brat DJ, Arbiser JL, Bellamkonda RV. (2012). Anti-invasive adjuvant therapy with imipramine blue enhances chemotherapeutic efficacy against glioma. Sci Trans Med 4:127ra36.

Zerrouqi A, Pyrzynska B, Febbraio M, Brat DJ, Van Meir EG. (2012) P14ARF inhibits human glioblastoma-induced angiogenesis by the upregulating the expression of TIMP3. J Clin Invest 122:1283-95.

Atif F, Sayeed I, Yousuf S, Ishrat T, Hua F, Wang J, Brat DJ, Stein DG. (2011) Progesterone inhibits the growth of human neuroblastoma: in vitro and in vivo evidence. Mol. Med. 17:1084-94.

Castellino R, Barwick B, Schniederjan M , Buss M, Becher O, Hambardzumyan D, McDonald T, Brat DJ, Durden D.(2010) Heterozygosity for Pten promotes tumorigenesis in a mouse model of medulloblastoma. PloS ONE 5(5):e10849.

Cooper L, Gutman D, Long Q, Johnson BA, Cholleti SR, Kurc T, Saltz JH, Brat DJ, Moreno CS. (2010) The proneural molecular signature is enriched in oligodendrogliomas and predicts improved survival among diffuse gliomas. PloS ONE 5: e12548.

Pieper AA, Xie S, Capota E, Estill SJ, Zhong J, Long JM, Becker GL, Huntington P, Goldman SE, Shen C-H, Capota M, Britt JK, Kotti T, Brat DJ, Williams NS, MacMillan KS, Naidoo J, Melito L, Hsieh J, De Brabander J, Ready JM, McKnight SL (2010) Discovery of a pro-neurogenic, neuroprotective chemical. Cell 142:39-51.

Rong Y, Belozerov V, Chen G, Tucker-Burden C, Durden DL, Van Meir EG, Mackman N, Brat DJ. (2009) EGFR and PTEN modulate tissue factor expression in glioblastoma through JunD/AP-1 transcriptional activity. Cancer Res 69:2450-49.

The Cancer Genome Atlas Network. (2008) Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 455:1061-1068.

Brat DJ, Prayson RA, Ryken TC, Olson JJ. (2008) Diagnosis of malignant glioma: role of neuropathology. J. Neuro-onc. 89:287-311

Tehrani M, Friedman TM, Olson JJ, Brat DJ. (2008) Intravascular thrombosis in central nervous system malignancies: A potential role in astrocytoma progression to glioblastoma. Brain Pathol 18:164-171.

Brat DJ, Parisi JE, Kleinschmidt-DeMasters BK, Yachnis AT, Montine TJ, Boyer PJ, Suzanne Z.-E. Powell SZE, Prayson RA, McLendon RE. (2008) Surgical Neuropathology Update: A Review of Changes Introduced by the World Health Organization (WHO) Classification of Tumors of the Central Nervous System, 4th Edition. Arch Pathol Lab Med 132:993-1007.

Tang X, Jang SW, Wang X, Liu Z, Bahr SM, Sun SY, Brat DJ, Gutmann DH, Ye K. (2007) Akt phosphorylation regulates the tumour-suppressor merlin through ubiquitination and degradation. Nat. Cell Biol 9:1199-207.

Brat DJ, Scheithauer BW, Fuller G, Tihan T. (2007) Newly codified glial neoplasms in the WHO classification of tumours of the central nervous system 2007: angiocentric glioma, pilomyxoid astrocytoma and pituicytoma. Brain Pathol. 17:319-24.

Brat DJ, Shehata BM. Castellano-Sanchez AA, Hawkins C, Yost RB, Greco C, Mazewski, C, Janss A, Ohgaki H, Perry A. (2007) Congenital glioblastoma: a clinico-pathologic and genetic analysis. Brain Pathol.17: 276-81.

Rong Y, Durden DL, Van Meir EG, Brat DJ (2006). "Pseudopalisading" necrosis in glioblastoma: a familiar morphologic finding that links vascular pathology, hypoxia, and angiogenesis. J. Neuropathol. Exp. Neurol. 65:529-39.

Khwaja FW, Nolen JDL, Mendrinos S, Lewis MM, Olson, JJ, Van Meir EG, Ritchie JC, Brat DJ. (2006). Proteomic analysis of cerebrospinal fluid discriminates malignant and non-malignant CNS disease and identifies specific protein markers. Proteomics 6:6277-87.

Rong Y, Hu F, Huang RP, Mackman N, Horowitz JM, Jensen RL, Durden DL, Van Meir EG, Brat DJ. (2006) Egr-1 regulates hypoxia-induced expression of tissue factor in glioblastoma through HIF-1 independent mechanisms. Cancer Res 66: 7067-74.

Brat DJ, Bellail AC, Van Meir EG. (2005) The role of interleukin-8 and its receptors in gliomagenesis and tumoral angiogenesis. Neuro-oncol. 7:122-133.

Rong Y, Post DE, Pieper RO, Durden DL, Van Meir EG, Brat DJ (2005) PTEN and hypoxia regulate tissue factor expression and plasma coagulation by glioblastoma. Cancer Res. 65:1406-13.

Pieper AA, Wu X, Han TW, Estill SJ, Wu L, Dang Q, Reece-Fincanon S, Dudley CA, Richardson J, Brat DJ, McKnight SL. (2005) The neuronal PAS domain protein 3 transcription factor controls FGF-mediated adult hippocampal neurogenesis in mice. Proc. Natl. Acad. Sci. U.S.A. 102:14052-7.

Brat DJ, Van Meir EG. (2004) Vaso-occlusive and pro-thrombotic mechanisms of tumor hypoxia, necrosis, and accelerated growth in glioblastoma. Lab Invest 84:397-405.

Brat DJ, Castellano-Sanchez A, Hunter SB, Pecot MJ, Cohen C, Hammond EH, Kaur B, Van Meir EG (2004). Pseudopalisading cells in glioblastoma are hypoxic, express extracellular matrix proteases, and are formed by a rapidly migrating population. Cancer Res. 64:920-7.

Brat, DJ, Seiferheld W, Perry A, Hammond E, Murray KJ, Schulsinger A, Mehta M, Curran W (2004). Analysis of 1p, 19q, 9p, and 10q as prognostic markers for high grade astrocytomas using fluorescence in situ hybridization on tissue micro-arrays from RTOG trials. Neuro-oncology 6:96-103.

Castellano-Sanchez AA, Li S, Qian J, Lagoo A, Weir E, Brat DJ. (2004) Central nervous system post-transplant lymphoproliferative disorders. Am. J. Clin. Pathol. 121:246-253.

Brat DJ, Mapstone TB. (2003) Malignant glioma physiology: cellular response to hypoxia and its role in tumor progression. Ann Intern Med 138:659-668.

Castellano-Sanchez AA, Ohgaki H, Yokoo H, Scheithauer BW, Burger PC, Hamilton RL Finkelstein SD, Brat DJ. (2003) Granular cell astrocytomas show a high frequency of allelic loss but are not a genetically defined subset. Brain Pathol 13:185-194.

Brat DJ, Castellano-Sanchez A, Kaur B, Van Meir EG. (2002) Genetic and biologic progression in astrocytomas and their relation to angiogenic dysregulation. Adv. Anat. Pathol. 9:24-36.

Brat DJ, Scheithauer BW, Medina-Florez R, Rosenblum MK, Burger PC. (2002) Infiltrative astrocytomas with granular cell features (granular cell astrocytomas): a study of morphology, grading, and outcome. Am J Surg Pathol 26:750-757.

Brat DJ, Van Meir EG. (2001) Glomeruloid microvascular proliferation orchestrated by VPF/VEGF: a new world of angiogenesis research. Am. J. Pathol. 158: 789-796.

Brat DJ, Scheithauer BW, Eberhart CG, Burger PC. (2001) Extra-ventricular neurocytomas: pathologic features and clinical outcome. Am. J. Surg. Pathol. 25:1252-1260.

Brat DJ, Scheithauer BW, Staugaitis SM, Holtzman RN, Morgello S, Burger PC. (2000) Pituicytoma: a distinctive low grade glioma of the neurohypophysis. Am. J. Surg. Pathol. 24:362-368.

Brat, D.J., Hirose, Y., Cohen, K.J., Feuerstein, B.G., Burger, P.C. (2000) Astroblastoma: clinicopathologic features and chromosomal abnormalities defined by comparative genomic hybridization. Brain Pathol. 10:342-352.

Brat DJ, James CD, Jedlicka AE, Connolly DC, Chang E, Castellani RJ, Schmid M, Schiller, M, Carson DA, Burger PC. (1999). Molecular genetic alterations in radiation-induced astrocytomas. Am. J. Pathol. 154:1431-1438.

Brat DJ, Giannini C, Scheithauer BW, Burger PC. (1999). Primary melanocytic neoplasms of the central nervous system. Am. J. Surg. Pathol. 23: 745-754.

Brat DJ, Scheithauer BW, Staugaitis SM, Cortez SC, Brecher K, Burger PC. (1998). Third ventricular "chordoid glioma": a distinct clinicopathologic entity. J. Neuropathol. Exp. Neurol. 57:283-290.

Book Chapters -

Louis DN, Reifenberger G, Brat DJ, Ellison DW. (2008) Tumours: Introduction and Neuroepithelial Tumours. In Love, S, Louis, DN and Ellison, D, eds. Greenfield's Neuropathology, 8th Edition, London: Hodder Arnold.

Wesseling P, Brat DJ, Fuller GN. (2007) Pituicytoma. In Louis DN, Ohgaki H, Weistler OD, and Cavenee WK, eds WHO Classification of Tumours of the Central Nervous System. 4th ed. Lyon: Intl. Agency for Research.

Brat DJ, VandenBerg SR, Figarella-Branger D, Taratuto AL. (2007) Desmoplastic infantile astrocytoma and ganglioglioma. In Louis DN, Ohgaki H, Weistler OD, and Cavenee WK, eds WHO Classification of Tumours of the Central Nervous System. 4th ed. Lyon: Intl. Agency for Research.

Kleihues P, Burger PC, Aldape K, Brat DJ, Biernat W, Bigner, DD, Nakazato Y, Plate KH , Giangaspero F, vonDeimling A, Ohgaki H, Cavenee WK. (2007) Glioblastoma. In Louis DN, Ohgaki H, Weistler OD, and Cavenee WK, eds. WHO Classification of Tumours of the Central Nervous System. 4th ed. Lyon: Intl. Agency for Research.

Brat DJ, Perry A. (2007) Melanocytic lesions. In Louis DN, Ohgaki H, Weistler OD, and Cavenee WK, eds WHO Classification of Tumours of the Central Nervous System. 4th ed. Lyon: Intl. Agency for Research.

Brat DJ, Scheithauer BW. (2007) Chordoid glioma of the third ventricle. In Louis DN, Ohgaki H, Weistler OD, and Cavenee WK, eds. WHO Classification of Tumours of the Central Nervous System. 4th ed. Lyon: Intl. Agency for Research.

Brat DJ (2006) Meningeal Melanocytoma, Neurocutaneous Melanosis, and Primary Meningeal Melanoma. In McLendon, RE, Bigner, DD, Rosenblum M and Bruner JM, eds. Russell and Rubinstein's Pathology of Tumors of the Nervous System, 7th Edition. London: Edward Arnold.

Brat DJ (2006) Chordoid Glioma of the Third Ventricle. In McLendon, RE, Bigner, DD, Rosenblum M and Bruner JM, eds. Russell and Rubinstein's Pathology of Tumors of the Nervous System, 7th Edition. London: Edward Arnold.

Brat DJ (2005) Overview of Anatomy and Histology of the Central Nervous System. In Prayson RA, ed. Foundations in Diagnostic Pathology, Neuropathology. Philadelphia: Churchill Livingstone.

Books Edited and Written -

Schneiderjan M, Brat DJ (2011) Biopsy Interpretation of Central Nervous System. Baltimore: Lippincott Williams & Wilkins.

Perry A, Brat DJ, eds. (2010) Practical Surgical Neuropathology: A Diagnostic Approach. Philadelphia: Churchill-Livingstone.