Charles G. Mullighan, MBBS(Hons), MSc, MD

Charles G. Mullighan, MBBS(Hons), MSc, MD

Assistant Member, St. Jude Faculty

Departments

Pathology

Contact Information

Charles Mullighan, MBBS(Hons), MSc, MD
Pathology
MS 342, Room D-4047E
St. Jude Children's Research Hospital
262 Danny Thomas Place
Memphis, TN 38105-3678
Email: charles.mullighan@stjude.org
Phone: (901) 595-3387
FAX: (901) 595-5947

Education

MBBS(Hons) - University of Adelaide (1993)
MSc - University of London (1997)
MD - University of Adelaide (1998)
Fellowship of the Royal College of Pathologists of Australasia – 2004
Fellowship of the Royal Australasian College of Physicians - 2004

Research Interests

  • The use of high-resolution, genome-wide approaches to identify genomic aberrations contributing to leukemogenesis and influencing leukemia outcome. These include microarray-based analysis of DNA copy number abnormalities, loss-of-heterozygosity, epigenetic changes, gene expression analysis, and microRNA profiling
  • The use of in vitro and in vivo experimental approaches to model genomic abnormalities in leukemogenesis
  • Genetics of disease susceptibility and disease phenotype, most notably the genetic determinants of allogeneic hematopoietic stem cell transplant outcome.

Selected Publications

Gutierrez A, Dahlberg SE, Neuberg DS, Zhang J, Grebliunaite R, Sanda T, Protopopov A, Tosello V, Kutok J, Larson RS, Borowitz MJ, Loh ML, Ferrando AA, Winter SS, Mullighan CG, Silverman LB, Chin L, Hunger SP, Sallan SE, Look AT. Absence of biallelic TCR? deletion predicts early treatment failure in pediatric T-cell acute lymphoblastic leukemia. J Clin Oncol July 19, 2010.

Holmfeldt L, Mullighan CG. PHF6 mutations in T-lineage acute lymphoblastic leukemia. Pediatr Blood Cancer June 29, 2010.

Stow P, Key L, Chen X, Pan Q, Neale GA, Coustan-Smith E, Mullighan CG, Zhou Y, Pui CH, Campana D. Clinical significance of low levels of minimal residual disease at the end of remission induction therapy in childhood acute lymphoblastic leukemia. Blood 115(23):4657-4663, 2010.

Mullighan CG. Genetic variation and the risk of acute lymphoblastic leukemia. Leuk Res June 8, 2010.

Kang H, Chen IM, Wilson CS, Bedrick EJ, Harvey RC, Atlas SR, Devidas M, Mullighan CG, Wang X, Murphy M, Ar K, Wharton W, Borowitz MJ, Bowman WP, Bhojwani D, Carroll WL, Camitta BM, Reaman GH, Smith MA, Downing JR, Hunger SP, Willman CL. Gene expression classifiers for relapse-free survival and minimal residual disease improve risk classification and outcome prediction in pediatric B-precursor acute lymphoblastic leukemia. Blood 115(7):1394-1205, 2010.

Mullighan CG, Collins-Underwood JR, Phillips LAA, Loudin MG, Liu W, Zhang J, Ma J, Coustan-Smith E, Harvey RC, Willman CL, Mikhail FM, Meyer J, Carroll AJ, Williams RT, Cheng J, Heerema NA, Basso G, Pession A, Pui CH, Raimondi SC, Hunger SP, Downing JR, Carroll WL, Rabin KR. Rearrangement of CRLF2 in B-progenitor- and Down syndrome-associated acute lymphoblastic leukemia. Nat Genet 41(11):1243-1246, 2009.

Mullighan CG. Genomic analysis of acute leukemia. Int J Lab Hematol May 18, 2009. [Epub ahead of print]

Viswanathan SR, Powers JT, Einhorn W, Hoshida Y, Ng TL, Toffanin S, O'Sullivan M, Lu J, Phillips LA, Lockhart VL, Shah SP, Tanwar PS, Mermel CH, Beroukhim R, Azam M, Teixeira J, Meyerson M, Hughes TP, Llovet JM, Radich J, Mullighan CG, Golub TR, Sorensen PH, Daley GQ. Lin28 promotes transformation and is associated with advanced human malignancies. Nat Genet May 31, 2009. [Epub ahead of print]

Mullighan CG, Zhang J, Harvey RC, Collins-Underwood JR, Schulman BA, Phillips LAA, Tasian SK, Loh ML, Su X, Liu W, Devidas M, Atlas SR, Chen I-M, Clifford RJ, Gerhard DS, Carroll WL, Reaman GH, Smith M, Downing JR, Hunger SP and Willman CL. JAK mutations in high-risk childhood acute lymphoblastic leukemia. Proc Natl Acad Sci USA May 22, 2009 [Epub ahead of print]

Fujisaki H, Kakuda H, Imai C, Mullighan CG, Campana D. Replicative potential of human natural killer cells. Br J Haematol 145(5):606-613, 2009.

Worthley DG, Ruszkiewicz A, Davies R, Moore S, Nivison-Smith I, To LB, Browett P, Western R, Durrant S, So J, Young GP, Mullighan CG, Bardy PG, Michael MZ. Human gastrointestinal neoplasia-associated myofibroblasts can develop from bone marrow-derived cells following allogeneic stem cell transplantation. Stem Cells 12:1463, 2009.

Mullighan CG and Downing JR. Genome-wide profiling of genetic alterations in acute lymphoblastic leukemia - recent insights and future directions. Leukemia Feb 26, 2009. [Epub ahead of print]

Coustan-Smith E, Mullighan CG, Onciu M, Behm FG, Raimondi SC, Pei D, Cheng C, Su X, Rubnitz JE, Basso G, Biondi A, Pui CH, Downing JR, Campana D. Early T-cell precursor leukaemia: a subtype of very high-risk acute lymphoblastic leukaemia. Lancet Oncol Feb;10(2):147-56, 2009.

Worthley DL, Johnson DF, Eisen DP, Dean MM, Heatley SL, Tung J, Scott J, Padbury RT, Harley HA, Bardy PG, Angus PW, Mullighan CG. Donor mannose-binding lectin deficiency increases the likelihood of clinically significant infection after liver transplantation. Clin Infect Dis Jan 1, 2009. [Epub ahead of print]

Mullighan CG, Su X, Zhang J, Radtke I, Phillips LA, Miller CB, Ma J, Liu W, Cheng C, Schulman BA, Harvey RC, Chen I-M, Clifford RJ, Carroll WL, Reaman G, Bowman WP, Devidas M, Gerhard DS, Yang W, Relling MV, Shurtleff SA, Campana D, Borowitz M, Pui C-H, Smith M, Hunger SP, Willman C, Downing JR, and the Children's Oncology Group. Deletion of IKZF1 and prognosis in acute lymphoblastic leukemia. N Engl J Med 360:470-80, 2009.

Mullighan CG, Downing JR. Global genomic characterization of acute lymphoblastic leukemia. Semin Hematol 46:3-15, 2009.

Pounds S, Cheng C, Mullighan C, Raimondi SC, Shurtleff S, Downing JR. Reference alignment of SNP microarray signals for copy number analysis of tumors. Bioinformatics 25:315-21, 2009.

French D, Yang W, Cheng C, Raimondi S, Mullighan CG, Downing JR, Evans WE, Pui C-H, Relling MV. Acquired variation outweighs inherited variation in whole genome analysis of methotrexate accumulation in leukemia. Blood 113:4512-20, 2009.

Mullighan CG. TET2 mutations in myelodysplasia and myeloid malignancies. Nat Genet 44(7):766-767, 2009.

Mullighan CG, Phillips LA, Su X, Ma J, Miller CB, Shurtleff SA, Downing JR. Genomic analysis of the clonal origins of relapsed acute lymphoblastic leukemia. Science 322:1377-80, 2008.

Mullighan CG. JAK2 - a new player in acute lymphoblastic leukemia. Lancet 372:1448-50, 2008

Mullighan CG, Williams RT, Downing JR, Sherr CJ. Failure of CDKN2A/B (INK4A/B-ARF)-mediated tumor suppression and resistance to targeted therapy in acute lymphoblastic leukemia induced by BCR-ABL1. Genes Dev 22:1411-5, 2008.

Mullighan CG, Downing JR. Ikaros and acute leukemia [review article]. Leuk Lymphoma 49:849-9, 2008.

Mullighan CG, Heatley SL, Danner S, Dean M, Doherty K, Hahn U, Bradstock KF, Minchinton RM, Schwarer AP, Szer J, Bardy PG. Mannose-binding lectin status is associated with risk of major infection following myeloablative sibling allogeneic hematopoietic stem cell transplantation. Blood 112:2120-8, 2008.

Mullighan CG, Miller CB, Radtke I, Phillips LA, Dalton J, Ma J, White D, Hughes TP, Le Beau MM, Pui C.-H., Relling MV, Shurtleff, SA, Downing JR. BCR-ABL1 lymphoblastic leukaemia is characterized by the deletion of Ikaros. Nature 453:110-114, 2008.

See also: ALL-SNP2

Mullighan CG, Kennedy A, Zhou X, Radtke I, Phillips LA, Shurtleff SA, Downing JR. Pediatric acute myeloid leukemia with nucleophosmin mutations is characterized by a gene expression profile with dysregulated HOX gene expression distinct from MLL-rearranged leukemias. Leukemia 21:2000-9, 2007.

Flotho C, Steinemann D, Mullighan CG, Neale G, Mayer K, Kratz CP, Schlegelberger B, Downing JR, Niemeyer CM. Genome-wide single-nucleotide polymorphism analysis in juvenile myelomonocytic leukemia identifies uniparental disomy surrounding the NF1 locus in cases associated with neurofibromatosis but not in cases with mutant RAS or PTPN11. Oncogene 26:5816, 2007.

Worthley DL, Bardy PG, Gordon DL, Mullighan CG. Mannose-binding lectin and gastric cancer. Int J Cancer 120:2751, 2007.

Mullighan CG, Goorha S, Radtke I, Miller CB, Coustan-Smith E, Dalton JD, Girtman K, Mathew S, Ma J, Pounds SB, Su X, Pui C-H, Relling MV, Evans WE, Shurtleff SA, Downing JR. Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia. Nature 446:758-64, 2007*.

See also: ALL-SNP1

*See also commentary in:
Wang Y, Armstrong SA. Genome-wide SNP analysis in cancer: leukemia shows the way. Cancer Cell 11:308, 2007.
Golub TR. Genomics: global views of leukaemia. Nature 446:739, 2007.

Worthley DL*, Mullighan CG*, Dean MM, Gordon DL, Phillips P, Heatley SL, Young GP, Bardy PG. Mannose-binding lectin deficiency does not increase the prevalence of Helicobacter pylori seropositivity. Eur J Gastroenterol and Hepatol 19:147-152, 2007.

Mullighan CG, Bogdanos D-P, Vergani D, Bardy PG. Cytochrome P450 1A2 is a target antigen in hepatitic graft-versus-host disease. Bone Marrow Transplant 38:703-5, 2006.

Worthley DL, Bardy PG, Angus P, Harley H, Mullighan CG. Mannose-binding lectin polymorphisms and liver transplantation. Gastroenterology 129:1805-6, 2005.

Annells MF, Hart PH, Mullighan CG, Heatley SL, Robinson JS, McDonald HM. Polymorphisms in immunoregulatory genes and the risk of histologic chorioamnionitis in Caucasoid women: a case control study. BMC Pregnancy Childbirth 21:4, 2005.

Annells MF, Hart PH, Mullighan CG, Heatley SL, Robinson JS, Bardy P, McDonald HM. Interleukins-1, -4, -6, -10, tumor necrosis factor, transforming growth factor-beta, FAS, and mannose-binding protein C gene polymorphisms in Australian women: Risk of preterm birth. Am J Obstet Gynecol 191:2056-67, 2004.

Mullighan CG, Rischbieth A, Duncan EM, Lloyd JV. Acquired isolated factor VII deficiency associated with severe bleeding and successful treatment with recombinant FVIIa (NovoSeven). Blood Coagul Fibrinolysis 15:347-51, 2004.

Mullighan CG, Heatley S, Doherty K, Szabo F, Grigg A, Hughes T, Schwarer A, Szer J, Tait B, To B, Bardy P. Non-HLA immunogenetic polymorphisms and the risk of complications after allogeneic hemopoietic stem-cell transplantation. Transplantation 77:587-96, 2004.

Jannes J, Haemilton-Bruce MA, Pilotto L, Smith B, Mullighan CG, Bardy PG, Koblar SA. Tissue plasminogen activator .–7351C/T enhancer polymorphism is a risk factor for lacunar stroke. Stroke 35:1090-4, 2004.

Mullighan CG, Heatley S, Lester S, Rischmueller M, Gordon T, Bardy P. Fas gene promoter polymorphisms in primary Sjogren’s syndrome. Ann Rheum Dis 63:98-101, 2004.

Helbig KJ, Heatley SL, Harris RJ, Mullighan CG, Bardy PG, Marmion BP. Variation in immune response genes and chronic Q fever. Concepts: preliminary test with post-Q fever fatigue syndrome. Genes Immun 4:82-5, 2003.

Last updated: July 2010

 

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