Photo of Christopher A. French,  MD

Christopher A. French, MD

Brigham And Women's Hospital

Brigham And Women's Hospital
Phone: (617) 525-4415
Fax: (617) 525-4422


cfrench@partners.org

Christopher A. French, MD

Brigham And Women's Hospital

EDUCATIONAL TITLES

  • Associate Professor, Pathology, Harvard Medical School
  • Associate Professor, Pathology, Brigham And Women's Hospital

Research Abstract

Our focus is on the NUT midline carcinoma (NMC), an uncommon, but uniformly lethal disease defined by the presence of BRD-NUT fusion oncogene, either BRD4-NUT or BRD3-NUT. We have found that BRD-NUT blocks differentiation and maintains the growth of carcinoma cells in vitro and in vivo. What is not known is the mechanism by which this occurs. One goal of our lab is to identify the molecular mechanisms of BRD-NUT-induced oncogenesis. We are currently performing structure-function and protein-binding assays to map functional domains and identify proteins that interact with BRD-NUT. To this, we are using a differentiation assay in a BRD-NUT-expressing cell line that contains an interchangeable, isogenic, tetracycline-inducible transgene. The other goal of our lab is to identify molecules that interfere with the BRD-NUT pathway. We currently preparing to perform a drug screen on BRD-NUT carcinoma cells, using differentiation as the readout. The results of these studies should not only identify critical components of the BRD-NUT mechanism, but also provide potential novel targeted therapies to this disease.

Publications

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  • Dragoescu E, French C, Cassano A, Baker S, Chafe W. NUT midline carcinoma presenting with bilateral ovarian metastases: a case report. Int J Gynecol Pathol 2015; 34:136-42. PubMed
  • French CA, Rahman S, Walsh EM, Kuhnle S, Grayson AR, Lemieux ME, Grunfeld N, Rubin BP, Antonescu CR, Zhang S, Venkatramani R, Dal Cin P, Howley PM. NSD3-NUT Fusion Oncoprotein in NUT Midline Carcinoma: Implications for a Novel Oncogenic Mechanism. 2014. PubMed
  • Wang R, Liu W, Helfer CM, Bradner JE, Hornick JL, Janicki SM, French CA, You J. Activation of SOX2 expression by BRD4-NUT oncogenic fusion drives neoplastic transformation in NUT midline carcinoma. Cancer Res 2014. PubMed
  • Puliyel MM, Mascarenhas L, Zhou S, Sapra A, Dal Cin P, French CA, Venkatramani R. Nuclear Protein in Testis Midline Carcinoma Misdiagnosed As Adamantinoma. J Clin Oncol 2014. PubMed
  • Parikh SA, French CA, Costello BA, Marks RS, Dronca RS, Nerby CL, Roden AC, Peddareddigari VG, Hilton J, Shapiro GI, Molina JR. NUT midline carcinoma: an aggressive intrathoracic neoplasm. J Thorac Oncol 2014; 8:1335-8. PubMed
  • French CA. The importance of diagnosing NUT midline carcinoma. Head Neck Pathol 2013; 7:11-6. PubMed
  • Russell SM, Lechner MG, Mokashi A, Megiel C, Jang JK, Taylor CR, Looijenga LH, French CA, Epstein AL. Establishment and characterization of a new human extragonadal germ cell line, SEM-1, and its comparison with TCam-2 and JKT-1. Urology 2013; 81:464.e1-9. PubMed
  • Bauer DE, Mitchell CM, Strait KM, Lathan CS, Stelow EB, Lüer SC, Muhammed S, Evans AG, Sholl LM, Rosai J, Giraldi E, Oakley RP, Rodriguez-Galindo C, London WB, Sallan SE, Bradner JE, French CA. Clinicopathologic Features and Long-term Outcomes of NUT Midline Carcinoma. Clin Cancer Res 2012; 18:5773-5779. PubMed
  • Wartchow EP, Moore TS, French CA, Mierau GW. Ultrastructural features of NUT midline carcinoma. Ultrastruct Pathol 2012; 36:280-4. PubMed
  • Fang W, French CA, Cameron MJ, Han YD, Liu HG. [Utility of NUT gene expression and rearrangement in diagnosis of NUT midline carcinoma in upper respiratory tract]. Zhonghua Bing Li Xue Za Zhi 2012; 41:519-24. PubMed
  • Evans AG, French CA, Cameron MJ, Fletcher CD, Jackman DM, Lathan CS, Sholl LM. Pathologic characteristics of NUT midline carcinoma arising in the mediastinum. Am J Surg Pathol 2012; 36:1222-7. PubMed
  • Fang W, French CA, Cameron MJ, Han Y, Liu H. Clinicopathological Significance of NUT Rearrangements in Poorly Differentiated Malignant Tumors of the Upper-Respiratory Tract. Int J Surg Pathol 2012. PubMed
  • Schwartz BE, Hofer MD, Lemieux ME, Bauer DE, Cameron MJ, West NH, Agoston ES, Reynoird N, Khochbin S, Ince TA, Christie A, Janeway KA, Vargas SO, Perez-Atayde AR, Aster JC, Sallan SE, Kung AL, Bradner JE, French CA. Differentiation of NUT Midline Carcinoma by Epigenomic Reprogramming. Cancer Res 2011; 71:2686-96. PubMed
  • Teo M, Crotty P, O'Sullivan M, French CA, Walshe JM. NUT Midline Carcinoma in a Young Woman. J Clin Oncol 2011. PubMed
  • Filippakopoulos P, Qi J, Picaud S, Shen Y, Smith WB, Fedorov O, Morse EM, Keates T, Hickman TT, Felletar I, Philpott M, Munro S, McKeown MR, Wang Y, Christie AL, West N, Cameron MJ, Schwartz B, Heightman TD, La Thangue N, French CA, Wiest O, Kung AL, Knapp S, Bradner JE. Selective inhibition of BET bromodomains. Nature 2010; 468:1067-73. PubMed
  • Fujioka N, French CA, Cameron MJ, Kratzke RA. Long-term survival of a patient with squamous cell carcinoma harboring NUT gene rearrangement. J Thorac Oncol 2010; 5:1704-5. PubMed
  • Reynoird N, Schwartz BE, Delvecchio M, Sadoul K, Meyers D, Mukherjee C, Caron C, Kimura H, Rousseaux S, Cole PA, Panne D, French CA, Khochbin S. Oncogenesis by sequestration of CBP/p300 in transcriptionally inactive hyperacetylated chromatin domains. EMBO J 2010; 29:2943-52. PubMed
  • Nelson BA, Lee EY, French CA, Bauer DE, Vargas SO. BRD4-NUT Carcinoma of the Mediastinum in a Pediatric Patient: Multidetector Computed Tomography Imaging Findings. J Thorac Imaging 2010; 25:W93-6. PubMed
  • French CA. Demystified molecular pathology of NUT midline carcinomas. J Clin Pathol 2010; 63:492-6. PubMed
  • Bellizzi AM, Bruzzi C, French CA, Stelow EB. The cytologic features of NUT midline carcinoma. Cancer Cytopathol 2009; 117:508-15. PubMed
  • Hsieh MS, French CA, Liang CW, Hsiao CH. NUT Midline Carcinoma: Case Report and Review of the Literature. Int J Surg Pathol 2009. PubMed
  • den Bakker MA, Beverloo BH, van den Heuvel-Eibrink MM, Meeuwis CA, Tan LM, Johnson LA, French CA, van Leenders GJ. NUT midline carcinoma of the parotid gland with mesenchymal differentiation. Am J Surg Pathol 2009; 33:1253-8. PubMed
  • Haack H,Johnson LA,Fry CJ,Crosby K,Polakiewicz RD,Stelow EB,Hong SM,Schwartz BE,Cameron MJ,Rubin MA,Chang MC,Aster JC,French CA. Diagnosis of NUT Midline Carcinoma Using a NUT-specific Monoclonal Antibody. Am J Surg Pathol 2009; 33:984-91. PubMed
  • Stelow EB, French CA. Carcinomas of the upper aerodigestive tract with rearrangement of the nuclear protein of the testis (NUT) gene (NUT midline carcinomas). Adv Anat Pathol 2009; 16:92-6. PubMed
  • French CA,Fletcher JA,Cibas ES,Caulfield C,Allard P,Kroll TG. Molecular detection of PPAR gamma rearrangements and thyroid carcinoma in preoperative fine-needle aspiration biopsies. Endocr Pathol 2008; 19:166-74. PubMed
  • Benitez GL, Gandia-Herrero F, Graham S, Larson TR, McQueen-Mason SJ, French CE, Rylott EL, Bruce NC. Engineering a Catabolic Pathway in Plants for the Degradation of 1,2-Dichloroethane. Plant Physiol 2008; 147:1192-8. PubMed
  • French CT, Lao P, Loraine AE, Matthews BT, Yu H, Dybvig K. Large-Scale Transposon Mutagenesis of Mycoplasma pulmonis. Mol Microbiol 2008; 69:67-76. PubMed
  • Stelow EB, Bellizzi AM, Taneja K, Mills SE, Legallo RD, Kutok JL, Aster JC, French CA. NUT Rearrangement in Undifferentiated Carcinomas of the Upper Aerodigestive Tract. Am J Surg Pathol 2008; 32:828-34. PubMed
  • French CA, Ramirez CL, Kolmakova J, Hickman TT, Cameron MJ, Thyne ME, Kutok JL, Toretsky JA, Tadavarthy AK, Kees UR, Fletcher JA, Aster JC. BRD-NUT oncoproteins: a family of closely related nuclear proteins that block epithelial differentiation and maintain the growth of carcinoma cells. Oncogene 2008; 27:2237-42. PubMed
  • Groszer M, Keays DA, Deacon RM, de Bono JP, Prasad-Mulcare S, Gaub S, Baum MG, French CA, Nicod J, Coventry JA, Enard W, Fray M, Brown SD, Nolan PM, Paabo S, Channon KM, Costa RM, Eilers J, Ehret G, Rawlins JN, Fisher SE. Impaired synaptic plasticity and motor learning in mice with a point mutation implicated in human speech deficits. Curr Biol 2008; 18:354-62. PubMed
  • French CE, Bell JM, Ward FB. Diversity and distribution of hemerythrin-like proteins in prokaryotes. FEMS Microbiol Lett 2007; 279:131-45. PubMed
  • Thompson T, Keogh E, French CC, Davis R. Anxiety sensitivity and pain: generalisability across noxious stimuli. Pain 2007; 134:187-96. PubMed
  • Mertens F, Wiebe T, Adlercreutz C, Mandahl N, French CA. Successful treatment of a child with t(15;19)-positive tumor. Pediatr Blood Cancer 2006; 49:1015-7. PubMed
  • Gabriele ML, Shahmoradian SH, French CC, Henkel CK, McHaffie JG. Early segregation of layered projections from the lateral superior olivary nucleus to the central nucleus of the inferior colliculus in the neonatal cat. Brain Res 2007; 1173:66-77. PubMed
  • French CA, Kutok JL, Faquin WC, Toretsky JA, Antonescu CR, Griffin CA, Nose V, Vargas SO, Moschovi M, Tzortzatou-Stathopoulou F, Miyoshi I, Perez-Atayde AR, Aster JC, Fletcher JA. Midline carcinoma of children and young adults with NUT rearrangement. J Clin Oncol 2004; 22:4135-9. PubMed
  • French CA, Miyoshi I, Kubonishi I, Grier HE, Perez-Atayde AR, Fletcher JA. BRD4-NUT fusion oncogene: a novel mechanism in aggressive carcinoma. Cancer Res 2003; 63:304-7. PubMed
  • French CA, Miyoshi I, Aster JC, Kubonishi I, Kroll TG, Dal Cin P, Vargas SO, Perez-Atayde AR, Fletcher JA. BRD4 bromodomain gene rearrangement in aggressive carcinoma with translocation t(15;19). Am J Pathol 2001; 159:1987-92. PubMed
  • Shehata BM, Steelman CK, Abramowsky CR, Olson TA, French CA, Saxe DF, Ricketts RR, Katzenstein HM. NUT midline carcinoma in a newborn with multiorgan disseminated tumor and a 2-year-old with a pancreatic/hepatic primary. Pediatr Dev Pathol 2011; 13:481-5. PubMed
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