Markus Muschen - Profile Photo

Markus Müschen, M.D., Ph.D.

  • Norman and Sadie Lee Foundation Endowed Professor in Pediatrics
  • Chair, Department of Systems Biology
  • Associate Director of Pediatric Oncology, Comprehensive Cancer Center
  • Howard Hughes Medical Institute Faculty Scholar

Markus Müschen, M.D., Ph.D.

Research Focus :
  • Pediatric Acute Lymphoblastic Leukemia (ALL)
  • Pediatric oncology
Other Languages Spoken
  • German
  • French

Markus Müschen, M.D., Ph.D., is the founding chair of the Department of Systems Biology within Beckman Research Institute, and holds the Norman and Sadie Lee Foundation Professorship in Pediatrics. Dr. Müschen is also the associate director of pediatric oncology of the comprehensive cancer center.

Dr. Müschen is a Howard Hughes Medical Institute Faculty Scholar and is supported by a National Cancer Institute Outstanding Investigator Award (R35). He received his medical degree from the Heinrich-Heine-Universität in Düsseldorf, Germany, where he graduated summa cum laude. He completed his medical training in hematology-oncology in Cologne, under Volker Diehl.

After scientific training at the Institute Pasteur in Paris, in Ralf Küppers’ and Klaus Rajewsky’s laboratory at the Institute of Genetics in Cologne and Janet Rowley’s laboratory at the University of Chicago, Dr. Müschen launched his laboratory in Cologne and moved with his entire group to the University of Southern California in 2005 as program leader, Hematological Malignancies Program, USC Norris Comprehensive Cancer Center and Children’s Hospital Los Angeles.

Dr. Müschen received a Scholar Award from the Leukemia & Lymphoma Society, a Stand Up to Cancer Innovation Award from the American Association for Cancer Research, a Senior Investigator Award from the Welcome Trust and held the 2012 Sir Alexander Haddow Professorship of the Institute of Cancer Research in London. From 2010 to 2017, Dr. Müschen was a tenured professor of Laboratory Medicine, Pathology and Medicine at the University of California San Francisco (UCSF) and served as program leader of the Hematological Malignancies Program of the UCSF Comprehensive Cancer Center.

Dr. Müschen and his colleagues have developed a comprehensive research program that will predict relapse of acute lymphoblastic leukemia (ALL) and a drug-discovery program that will help to prevent or overcome ALL relapse in children.

  • 2017 - present, Chair, Department of Systems Biology, Beckman Research Institute of City of Hope, Duarte, CA
  • 2017 - present, Norman and Sadie Lee Foundation Endowed Professor in Pediatrics, City of Hope, Duarte, CA
  • 2017 - present, Associate Director of Pediatric Oncology, Comprehensive Cancer Center, City of Hope, Duarte, CA
  • 2010 - 2017, Professor (ladder rank, with tenure), University of California, San Francisco, Department of Laboratory Medicine, and Department of Pathology, San Francisco, CA
  • 2012 - 2017, Program Leader, Hematological Malignancies Program, UCSF Comprehensive Cancer Center, San Francisco, CA
  • 2008 - 2010, Associate Professor with tenure, University of Southern California and Children’s Hospital Los Angeles, Los Angeles, CA
  • 2005 - 2008, Tenure-track Associate Professor (tenure-track), University of Southern California and Children’s Hospital Los Angeles, Los Angeles, CA.

Degrees

  • 1999, Heinrich-Heine-Universitat Dusseldorf, M.D., Helmut Sies
  • 2003, Institute for Genetics, University of Cologne, M.D., Ph.D., Ralf Kuppers, Klaus Rajewsky
  • Chan LN, Chen Z, Braas D, Lee JW, Xiao G, Geng H, Cosgun KN, Hurtz C, Shojaee S, Cazzaniga V, Schjerven H, Ernst T, Hochhaus A, Kornblau SM, Konopleva M, Pufall MA, Cazzaniga G, Liu GJ, Milne TA, Koeffler HP, Ross TS, Sánchez-García I, Borkhardt A, Yamamoto KR, Dickins RA, Graeber TG and Müschen M. Metabolic gatekeeper function of B-lymphoid transcription factors. Nature. 2017 Feb 23; 542 (7642):479-483.
  • Schjerven H, Ayongaba EF, Aghajanirefah A, McLaughlin J, Cheng D, Geng H, Boyd JR, Eggesbø LM, Lindeman I, Heath JL, Park E, Witte ON, Smale ST, Frietze S and Müschen M. Genetic analysis of Ikaros target genes and tumor suppressor function in BCR-ABL1+ pre-B ALL. J Exp Med. 2017 Mar 6; 214 (3):793-814.
  • Katerndahl CD, Heltemes-Harris LM, Willette MJ, Henzler CM, Frietze S, Yang R, Schjerven H, Silverstein KA, Ramsey LB, Hubbard G, Wells AD, Kuiper RP, Scheijen B, van Leeuwen FN, Müschen M, Kornblau SM and Farrar MA. Antagonism of B cell enhancer networks by STAT5 drives leukemia and poor patient survival. Nature Immunol. 2017 Apr 3. doi: 10.1038/ni.3716.
  • Xu L, Chen Y, Dutra-Clarke M, Mayakonda A, Hazawa M, Savinoff SE, Doan N, Said JW, Yong WH, Watkins A, Yang H, Ding LW, Jiang YY, Tyner JW, Ching J, Kovalik JP, Madan V, Chan SL, Müschen M, Breunig JJ, Lin DC and Koeffler HP. BCL6 promotes glioma and serves as a therapeutic target. Proc Natl Acad Sci U S A. 2017 Mar 29. pii: 201609758.
  • Graham NA, Minasyan A, Lomova A, Cass A, Balanis NG, Friedman M, Chan S, Zhao S, Delgado A, Go J, Beck L, Hurtz C, Ng C, Qiao R, Ten Hoeve J, Palaskas N, Wu H, Müschen M, Multani AS, Port E, Larson SM, Schultz N, Braas D, Christofk HR, Mellinghoff IK and Graeber TG. Recurrent patterns of DNA copy number alterations in tumors reflect metabolic selection pressures. Mol Syst Biol. 2017 Feb 15;13(2):914.
  • Boulianne B, Robinson ME, May PC, Castellano L, Blighe K, Thomas J, Reid A, Müschen M, Apperley JF, Stebbing J and Feldhahn N. Lineage-Specific Genes Are Prominent DNA Damage Hotspots during Leukemic Transformation of B Cell Precursors. Cell Rep. 2017 Feb 14;18(7):1687-1698
  • Kim E, Hurtz C, Koehrer S, Wang Z, Balasubramanian S, Chang BY, Müschen M, Davis RE and Burger JA. Ibrutinib inhibits pre-BCR+ B-cell acute lymphoblastic leukemia progression by targeting BTK and BLK. Blood. 2017 Mar 2;129 (9):1155-1165.
  • Townsend EC, Murakami MA, Christodoulou A, Christie AL, Köster J, DeSouza TA, Morgan EA, Kallgren SP, Liu H, Wu SC, Plana O, Montero J, Stevenson KE, Rao P, Vadhi R, Andreeff M, Armand P, Ballen KK, Barzaghi-Rinaudo P, Cahill S, Clark RA, Izraeli S, Jacobsen ED, Jacobson CA, Jeay S, Jeremias I, Kelliher MA, Koch R, Konopleva M, Kopp N, Kornblau SM, Kung AL, Kupper TS, LeBoeuf NR, LaCasce AS, Lees E, Li LS, Look AT, Murakami M, Müschen M, Neuberg D, Ng SY, Odejide OO, Orkin SH, Paquette RR, Place AE, Roderick JE, Ryan JA, Sallan SE, Shoji B, Silverman LB, Soiffer RJ, Steensma DP, Stegmaier K, Stone RM, Tamburini J, Thorner AR, van Hummelen P, Wadleigh M, Wiesmann M, Weng AP, Wuerthner JU, Williams DA, Wollison BM, Lane AA, Letai A, Bertagnolli MM, Ritz J, Brown M, Long H, Aster JC, Shipp MA, Griffin JD and Weinstock DM. The Public Repository of Xenografts Enables Discovery and Randomized Phase II-like Trials in Mice. Cancer Cell. 2016 Apr 11;29(4):574-86.
  • Shojaee S, Chan LN, Buchner M, Cazzaniga V, Cosgun KN, Geng H, Qiu YH, von Minden MD, Ernst T, Hochhaus A, Cazzaniga G, Melnick A, Kornblau SM, Graeber TG, Wu H, Jumaa H, and Müschen M. PTEN opposes negative selection and enables oncogenic transformation of pre-B cells. Nature Med. 2016 Apr;22(4):379-87.
  • Dasgupta Y, Koptyra M, Hoser G, Kantekure K, Roy D, Gornicka B, Nieborowska-Skorska M, Bolton-Gillespie E, Cerny-Reiterer S, Müschen M, Valent P, Wasik MA, Richardson C, Hantschel O, van der Kuip H, Stoklosa T and Skorski T. Normal ABL1 is a tumor suppressor and therapeutic target in human and mouse leukemias expressing oncogenic ABL1 kinases. Blood. 2016 Apr 28;127(17):2131-43.
  • Benito JM, Godfrey L, Kojima K, Hogdal L, Wunderlich M, Geng H, Marzo I, Harutyunyan KG, Golfman L, North P, Kerry J, Ballabio E, Chonghaile TN, Gonzalo O, Qiu Y, Jeremias I, Debose L, O'Brien E, Ma H, Zhou P, Jacamo R, Park E, Coombes KR, Zhang N, Thomas DA, O'Brien S, Kantarjian HM, Leverson JD, Kornblau SM, Andreeff M, Müschen M, Zweidler-McKay PA, Mulloy JC, Letai A, Milne TA and Konopleva M. MLL-Rearranged Acute Lymphoblastic Leukemias Activate BCL-2 through H3K79 Methylation and Are Sensitive to the BCL-2-Specific Antagonist ABT-199. Cell Rep. 2015 Dec 29;13(12):2715-27.
  • Greaves M and Müschen M. Infection and the Perils of B-cell Activation. Cancer Discov. 2015 Dec;5(12):1244-6.
  • Jones CL, Gearheart CM, Fosmire S, Delgado-Martin C, Evensen NA, Bride K, Waanders AJ, Pais F, Wang J, Bhatla T, Bitterman DS, de Rijk SR, Bourgeois W, Dandekar S, Park E, Burleson TM, Madhusoodhan PP, Teachey DT, Raetz EA, Hermiston ML, Müschen M, Loh ML, Hunger SP, Zhang J, Garabedian MJ, Porter CC and Carroll WL. MAPK signaling cascades mediate distinct glucocorticoid resistance mechanisms in pediatric leukemia. Blood. 2015 Nov 5;126(19):2202-12
  • Song C, Gowda C, Pan X, Ding Y, Tong Y, Tan BH, Wang H, Muthusami S, Ge Z, Sachdev M, Amin SG, Desai D, Gowda K, Gowda R, Robertson GP, Schjerven H, Muschen M, Payne KJ and Dovat S. Targeting casein kinase II restores Ikaros tumor suppressor activity and demonstrates therapeutic efficacy in high-risk leukemia. Blood. 2015 Oct 8;126(15):1813-22.
  • Shojaee S, Caeser R, Buchner M, Park E, Swaminathan S, Hurtz C, Geng H, Chan LN, Klemm L, Hofmann WK, Qiu YH, Zhang N, Coombes KR, Paietta E, Molkentin J, Koeffler HP, Willman CL, Hunger SP, Melnick A, Kornblau SM and Müschen M. Erk Negative Feedback Control Enables Pre-B Cell Transformation and Represents a Therapeutic Target in Acute Lymphoblastic Leukemia. Cancer Cell. 2015 Jul 13;28(1):114-28
  • Swaminathan S, Klemm L, Park E, Papaemmanuil E, Ford A, Kweon SM, Trageser D, Hasselfeld B, Henke N, Mooster J, Geng H, Schwarz K, Kogan SC, Casellas R, Schatz DG, Lieber MR, Greaves MF and Müschen M. Mechanisms of clonal evolution in childhood acute lymphoblastic leukemia. Nature Immunol. 2015; 16: 766-74.
  • Müschen M. Ph+ ALL: drawing strength from a benign past. Blood. 2015; 125: 2879-80.
  • Müschen M. Rationale for targeting the pre-B-cell receptor signaling pathway in acute lymphoblastic leukemia. Blood. 2015; 125: 3688-93
  • Chen Z, Shojaee S, Buchner M, Geng H, Lee JW, Klemm L, Titz B, Graeber TG, Park E, Tan YX, Satterthwaite A, Paietta E, Hunger SP, Willman CL, Melnick A, Loh ML, Jung JU, Coligan JE, Bolland S, Mak TW, Limnander A, Jumaa H, Reth M, Weiss A, Lowell CA and Müschen M. Signalling thresholds and negative B-cell selection in acute lymphoblastic leukaemia. Nature. 2015; 521: 357-61.
  • Geng H, Hurtz C, Lenz KB, Chen Z, Baumjohann D, Thompson S, Goloviznina NA, Chen WY, Huan J, LaTocha D, Ballabio E, Xiao G, Lee JW, Deucher A, Qi Z, Park E, Huang C, Nahar R, Kweon SM, Shojaee S, Chan LN, Yu J, Kornblau SM, Bijl JJ, Ye BH, Ansel KM, Paietta E, Melnick A, Hunger SP, Kurre P, Tyner JW, Loh ML, Roeder RG, Druker BJ, Burger JA, Milne TA, Chang BH and Müschen M. Self-enforcing feedback activation between BCL6 and pre-B cell receptor signaling defines a distinct subtype of acute lymphoblastic leukemia. Cancer Cell. 2015; 27: 409-25
  • Buchner M, Park E, Geng H, Klemm L, Flach J, Passegué E, Schjerven H, Melnick A, Paietta E, Kopanja D, Raychaudhuri P and Müschen M. Identification of FOXM1 as a therapeutic target in B-cell lineage acute lymphoblastic leukaemia. Nat Commun. 2015; 6: 6471.
  • Lu Z, Lieber MR, Tsai AG, Pardo CE, Müschen M, Kladde MP and Hsieh CL. Human lymphoid translocation fragile zones are hypomethylated and have accessible chromatin. Mol Cell Biol. 2015 Apr;35(7):1209-22
  • Buchner M, Swaminathan S, Chen Z and Müschen M. Mechanisms of pre-B-cell receptor checkpoint control and its oncogenic subversion in acute lymphoblastic leukemia. Immunol Rev. 2015 Jan;263(1):192-209.
  • Swaminathan S and Müschen M. Follicular lymphoma: too many reminders for a memory B cell. J Clin Invest. 2014; 124: 5095-8
  • Kharabi Masouleh B, Geng H, Hurtz C, Chan LN, Logan AC, Chang MS, Huang C, Swaminathan S, Sun H, Paietta E, Melnick AM, Koeffler P and Müschen M. Mechanistic rationale for targeting the unfolded protein response in pre-B acute lymphoblastic leukemia. Proc Natl Acad Sci U S A. 2015 May 27;111(21):E2219-28.
  • Papaemmanuil E, Rapado I, Li Y, Potter NE, Wedge DC, Tubio J, Alexandrov LB, Van Loo P, Cooke SL, Marshall J, Martincorena I, Hinton J, Gundem G, van Delft FW, Nik-Zainal S, Jones DR, Ramakrishna M, Titley I, Stebbings L, Leroy C, Menzies A, Gamble J, Robinson B, Mudie L, Raine K, O'Meara S, Teague JW, Butler AP, Cazzaniga G, Biondi A, Zuna J, Kempski H, Müschen M, Ford AM, Stratton MR, Greaves M and Campbell PJ. RAG-mediated recombination is the predominant driver of oncogenic rearrangement in ETV6-RUNX1 acute lymphoblastic leukemia. Nature Genet. 2014; 46: 116-25.
  • Swaminathan S, Huang C, Geng H, Chen Z, Harvey R, Kang H, Ng C, Titz B, Hurtz C, Sadiyah MF, Nowak D, Thoennissen GB, Rand V, Graeber TG, Koeffler HP, Carroll WL, Willman CL, Hall AG, Igarashi K, Melnick A and Müschen M. BACH2 mediates negative selection and p53-dependent tumor suppression at the pre-B cell receptor checkpoint. Nature Med. 2013; 19: 1014-22.
  • Duy C, Hurtz C, Shojaee S, Cerchietti L, Geng H, Swaminathan S, Klemm L, Kweon SM, Nahar R, Braig M, Park E, Kim YM, Hofmann WK, Herzog S, Jumaa H, Koeffler HP, Yu JJ, Heisterkamp N, Graeber TG, Wu H, Ye BH, Melnick A and Müschen M. BCL6 enables Ph+ acute lymphoblastic leukaemia cells to survive BCR-ABL1 kinase inhibition. Nature. 2012; 473: 384-8.
  • Hurtz C, Hatzi K, Cerchietti L, Braig M, Park E, Kim YM, Herzog S, Ramezani-Rad P, Jumaa H, Müller MC, Hofmann WK, Hochhaus A, Ye BH, Agarwal A, Druker BJ, Shah NP, Melnick AM and Müschen M. BCL6-mediated repression of p53 is critical for leukemia stem cell survival in chronic myeloid leukemia. J Exp Med. 2012; 208: 2163-74.
  • 1994 - 2004, German Society for Molecular Biology and Biochemistry
  • 2004 - present, German Society of Immunologists
  • 2007 - present, American Society of Hematology
  • 2009 - present, American Association for Cancer Research
  • 2016, HHMI Faculty Scholar Award, Howard Hughes Medical Institute
  • 2015, NCI Outstanding Investigator Award (R35CA197628), National Cancer Institute
  • 2014, Senior Investigator Award, Wellcome Trust, UK
  • 2012, Sir Alexander Haddow professorship, The Institute of Cancer Research (ICR) and University of London, London, UK
  • 2011, AACR Stand-up-to-Cancer Innovation Award, American Association of Cancer Research (AACR)
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