Atlanta, GA 30322
404 712-1266 Phone
Vice Chair, Translational Programs, Department of Pathology and Laboratory Medicine
Co-Director, Pathology Residency Program, Emory University School of Medicine
Director, Cancer Tissue and Pathology Shared Resource, Winship Cancer Institute
Director, Neuropathology Fellowship, Emory University School of Medicine
Director, Neuropathology Division, Emory University School of Medicine
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
- 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 and Notch1.
My clinical interest is diagnostic neuropathology 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. This involves histopathologic assessment as well as the use of advance molecular diagnostic techniques. I also direct the Neuropathology Fellowship and co-direct the Pathology Residency Program, with an emphasis on recruitment and career development.
American Board of Pathology, Neuropathology Test Development and Advisory Committee, 2016-
Education Committee, United States and Canadian Academy of Pathology, 2016-
Lifetime Achievement Award for Meritorious Service, College of American Pathologists (CAP), 2016
Expert Panel, American Joint Commission on Cancer (AJCC) Cancer Staging Manual, 8th Edition, 2015-
Mentor of the Year, Post-doctoral Education, Emory University School of Medicine, 2015
American Society for Clinical Investigation (ASCI), 2014-
Board of Directors, Society for Neuro-oncology, 2014-
Council on Scientific Affairs, College of American Pathologists (CAP), 2013-16
Executive Council, American Association of Neuropathologists (AANP), 2013-
Woodruff Health Sciences Center Leadership Academy, 2010
Georgia Research Alliance Distinguished Cancer Scientist, 2009
Lower Grade Gliomas (Chair) and Glioblastoma Working Groups, The Cancer Genome Atlas (TCGA) Project, National Cancer Institute (NCI), 2008-2015
Neuropathology Committee (Chair), College of American Pathologists, 2006-2016
Advisory Committee, World Health Organization Classification of Brain Tumors, 2006
Lucien J. Rubinstein Award, American Association of Neuropathologists, 2004
Editorial Boards: Journal of Neuropathology and Experimental Neurology, Brain Pathology, Archives of Pathology and Laboratory Medicine, 2000-
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
1997 Diplomate, Anatomic Pathology, American Board of Pathology
1999 Diplomate, Neuropathology, American Board of Pathology
Ceccarelli M, Barthel FP, Malta TM, Sabedot TS, Pagnotta SM, Murray BA, Radenbaugh A, Morozova O, Newton Y, Anjum S,, Wang J, Manyam G, Brat DJ, Zoppoli P, Akbani R, Ling S, Cherniack AD, Zhang H, Poisson L, Rao A, Mikkelsen T, Yung WKA, Huse J, Rao G, Lau CC, Rao A, Grifford M, Wrensch M, Beroukhim R, Cooper L, Rabadan R, Aldape KD, Laird PW, Gutmann DH, Salama SR, Noushmehr H, Iavarone A, Verhaak RGW, TCGA Research Network (2016) Integrated characterization of genomic, epigenomic and transcriptomic activities reveals novel relationships between histological subtypes and molecular signatures in diffuse low- and high-grade glioma. Cell 164:550-63.
Selagea L, Mishra A, Anand M, Ross J, Tucker-Burden C, Kong J, Brat DJ. (2016) EGFR and C/EBP-ß oncogenic signaling is bidirectional in human glioma and varies with C/EBP-ß isoform. FASEB J. 12:4098-4108.
Mukherjee S, Tucker-Burden C, Zhang C, Moberg K, Read R, Costas G. Hadjipanayis CG, Brat, DJ. (2016) Drosophila Brat and human ortholog TRIM3 maintain stem cell equilibrium and suppress brain tumorigenesis by attenuating Notch nuclear transport. Cancer Res 76:2443-52.
Brat DJ, Verhaak RGW, Aldape KD, Yung WKA, et al. The Cancer Genome Research Network (2015). Comprehensive and Integrative Genomic Characterization of Diffuse Lower Grade Gliomas. N Eng J Med 372:2481-98.
Brat DJ, Cagle P, Dillon D, Hattab E, McLendon RE, Miller MA, Buckner JC. (2015) Template for reporting results of biomarker testing of specimens from patients with tumors of the central nervous system. Arch Pathol Lab Med 139:1087-93.
Mukherjee S, Kong J, Brat DJ. (2015). Cancer stem cell division: when the rules of asymmetry are broken. Stem Cells Dev 24:405-16.
Appin CL, Brat DJ (2015) Biomarker-Driven Diagnosis of Diffuse Gliomas. Mol Aspects Med. 3:2 doi:10.1016/j.mam.2015.05.002
Chen G, Kong J, Tucker-Burden C, Anand M, Rong Y, Rahman F, Moreno CS, Van Meir EG, Hadjipanayis CG, Brat DJ. (2014) Human Brat ortholog TRIM3 is a tumor suppressor that regulates asymmetric cell division in glioblastoma. Cancer Res. 74:4536-48.
He K, Qi Qi, Chan C-B, Xiao G, Liu X,Tucker-Burden C, Wang L, Mao H, Tao H, Sun S-Y, Lu X, McDonald FE, Luo H, Fan Q, Sun, S-Y, Weiss WA, Brat DJ, Ye K. (2013) Blockade of glioma proliferation via allosteric inhibition of JAK2. Sci. Signal. 6, ra55.
Kong J, Cooper LAD, Wang F, Gao J, Teodoro G, Schniederjan MJ, Scarpace L, Mikkelsen T, Moreno CS, Saltz JH, Brat DJ. (2013) Machine-based morphologic analysis of glioblastoma using whole-slide pathology images uncovers clinically relevant molecular correlates. PloS ONE 8(11):e81049.
Brennan CW et al. TCGA Research Network (2013). The somatic genomic landscape of glioblastoma. Cell 155:462-477.
Rutledge WC, Kong J, Gao J, Gutman DA, Cooper LAD, Appin C, Park Y, Scarpace L, Mikkelsen T, Cohen M, Aldape K, McLendon R, Lehman N, Miller R, Schniederjan MJ, Brennan C, Saltz JH, Moreno CS, Brat DJ (2013) Tumor-infiltrating lymphocytes in glioblastoma are associated with specific genomic alterations and are related to transcriptional class. Clin Can Res 19:4951-60.
Singh D, Chan JM, Zoppoli P, Niola F, Sullivan R, Castano A, Liu EM, Reichel J, Porrati P, Pellegatta S, Qiu K, Gao Z, Ceccarelli M, Riccardi R, Brat DJ, Guha A, Aldape K, Golfinos JG, Zagzag D, Mikkelsen T, Finocchiaro G, Lasorella A, Rabadan R, Iavarone A.(2012) Transforming fusions of FGFR and TACC genes in human glioblastoma. Science 337:1231-1235.
Gutman DA, Cooper LAD, Hwang SN, Gao D, Holder CA, Aurora TD, Dunn Jr. W , Wintermark M, Scarpace L, Huang E, Jilwan M, Mikkelsen T, Jain R, Clifford RJ, Raghavan P, Hammoud D, Mongkolwat P, Freymann J, Moreno C, Kirby J, Krishnan A, Jaffe C, Dehkharghani S, Colom R, Saltz JH, Flanders A, Brat DJ. (2012) Magnetic resonance imaging predictors of molecular profile and survival: a multi-institutional study of the TCGA glioblastoma data set. Radiology 267:560-569.
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.
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.
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.
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.
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, Prayson RA, Ryken TC, Olson JJ. (2008) Diagnosis of malignant glioma: role of neuropathology. J. Neuro-onc. 89:287-311
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.
The Cancer Genome Atlas Network. (2008) Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 455:1061-1068.
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.
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.
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.
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.
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.
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.
Brat DJ, Mapstone TB. (2003) Malignant glioma physiology: cellular response to hypoxia and its role in tumor progression. Ann Intern Med 138:659-668.
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, Scheithauer BW, Eberhart CG, Burger PC. (2001) Extra-ventricular neurocytomas: pathologic features and clinical outcome. Am. J. Surg. Pathol. 25:1252-1260.
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, 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, 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 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, 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, 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.
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.