Pathology Faculty Member

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    Anatomic Pathology
    G167 EUH
    Atlanta, GA 30322
    404 712-1266 Phone

    For an expert Pathology consultation,
    or to send a specimen, call:

    1-404-712-5947


    Daniel J Brat, MD, PhD

    Cancer Biology
    Neuropathology

    Professor
    Pathology & Laboratory Medicine


    Pathology Faculty Photo

    Other Appointments/Positions

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

    Director, Cancer Tissue and Pathology Core, Winship Cancer Institute

    Neuropathology Attending, Emory Healthcare Hospitals

    Director, Neuropathology Division, Emory University School of Medicine

    Director, Neuropathology Fellowship, Emory University School of Medicine

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


    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 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. I also direct the Neuropathology Fellowship and co-direct the Pathology residency, with an emphasis on recruitment and career development.


    Honors / Awards:

    Board of Directors, Society for Neuro-oncology, 2014-

    Executive Council, American Association of Neuropathologists (AANP), 2013-

    Council on Scientific Affairs, College of American Pathologists (CAP), 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-

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

    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, Neurosurgery, Archives of Pathology and Laboratory Medicine, 2000-

    Pathology Committee, Radiation Therapy Oncology Group, 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

    Specialty Boards:

    1997 Diplomate, Anatomic Pathology, American Board of Pathology


    1999 Diplomate, Neuropathology, American Board of Pathology


    Selected Publications:

    Published and Accepted Research Articles -

    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.


    Brennan CW et al. TCGA Research Network (2013). The somatic genomic landscape of glioblastoma. Cell 155:462-477.


    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.


    Appin CL, Gao J, Chisolm C, Torian M, Alexis D, Vincentelli C, Schniederjan MJ, Hadjipanayis C, Olsen JJ, Hunter S, Hao C, Brat DJ (2013) Glioblastoma with oligodendroglial component (GBM-O): molecular genetic and clinical characteristics. Brain Pathol 23:454-61.


    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.


    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.


    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.


    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.


    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.


    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.


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


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


    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.


    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.


    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.


    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.


    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, 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, 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.


    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.


    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.


    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.


    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, 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.


    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 (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.