BS – Biology, University of Washington, Seattle, Washington (1995)
BS – Biochemistry, University of Washington, Seattle, Washington (1995)
PhD – Immunology, University of Southern California, Los Angeles, California (2001)
MD – Medicine, University of Southern California, Los Angeles, California (2003)
Research in my laboratory focuses on high risk leukemia including MLL-rearranged (MLLr) disease as well as acute megakaryoblastic leukemia (AMKL). We utilize comprehensive next generation sequencing approaches such as whole genome, exome, transcriptome and chromatin immunoprecipiation sequencing to characterize these malignancies at the genetic and epigenetic level. These efforts have led to the identification of CBFA2T3-GLIS2, a novel fusion gene that confers a poor prognosis in pediatric AMKL and a detailed view of the genomic landscape in MLLr leukemia. To understand the contribution of identified genomic lesions to transformation and progression of disease, we have established multiple leukemia mouse models that include conditional knock-ins, gene-modified syngeneic bone marrow transplants, as well as primary patient sample xenografts for mechanistic studies. The overall goal of our lab is to translate these findings into the clinic. To accomplish this, we collaborate with the department of chemical biology and therapeutics to screen large numbers of compounds in an unbiased manner and test them in our model systems, as well as to evaluate targeted drugs that are predicted to be effective based on the mutational landscape of a given leukemia. Using this approach, we have identified bortezomib and vorinostat as active agents in MLLr leukemia with a novel mechanism of action. These data formed the preclinical basis for a multi-institutional pilot clinical trial in newly diagnosed patients with infant acute lymphoblastic leukemia (TINI: Total therapy for infants with acute lymphoblastic leukemia).
Dang J, Nance S, Ma J, Cheng J, Walsh MP, Vogel P, Easton J, Song G, Rusch M, Gedman AL, Koss C, Downing JR, Gruber TA. AMKL chimeric transcription factors are potent inducers of leukemia. Leukemia Feb 8, 2017. doi: 10.1038/leu.2017.51. [Epub ahead of print].
de Rooij J, Branstetter C, Ma J, Li Y, Walsh MP, Cheng J, Obulkasim A, Easton J, Verboon LJ, Mulder HL, Rusch M, Lim J, Zimmermann M, Reinhardt K, Song G, Yeoh AEJ, Shih L-Y, Liang D-C, Halene S, Krause DS, Zhang J, Downing JR, Locatelli F, Reinhardt D, Van den Heuvel-Eibrink M, Zwaan CM, Fornerod M, Gruber TA. Pediatric non-Down Syndrome Acute Megakaryoblastic Leukemia is Characterized by Distinct Genomic Subsets with Varying Outcomes. Nat Genet 49:451-456, 2017.
Diamond EL, Durham BH, Haroche J, Yao Z, Ma J, Choi J, Kim E, Cohen-Aubart F, Lee S, Gao Y, Micol J-B, Campbell P, Walsh MP, Sylvester B, Dolgalev I, Aminova O, Heguy A, Zappile P, Nakitandwe J, Dalton JD, Ellison DW, Estrada-Veras J, Lacouture M, Chung YR, Rampal R, Pichardo J, Briggs S, Héritier S, Donadieu J, Solit DB, Hyman D, Baselga J, Janku F, Taylor BS, Park CY, Amoura Z, Dogan A, Emile J-F, Rosen N, Gruber TA, Abdel-Wahab O. Diverse and Targetable Kinase Alterations Drive Histiocytic Neoplasms. Cancer Discov 6:154-65, 2016.
Zhang J, Walsh MF, Wu G, Edmonson MN, Gruber TA, Easton J, Hedges D, Ma X, Zhou X, Yergeau DA, Wilkinson M, Vadodaria B, Chen X, McGee RB, Hines-Dowell S, Nuccio R, Quinn E, Shurtleff SA, Rusch M, Patel A, Becksfort JB, Weaver MS, Ding L, Mardis ER, Wilson RK, Pui C-H, Gajjar A, Ellison DW, Pappo AS, Nichols KE, Downing JR. Germline Mutations in Predisposition Genes in Pediatric Cancer. N Engl J Med 373:2336-46, 2015.
Andersson AK*, Ma J, Wang J, Chen X, Gedman AL, Dang J, Nakitandwe J, Holmfeldt L, Parker M, Easton J, Huether R, Kriwacki R, Rusch M, Wu G, Li Y, Mulder H, Raimondi S, Pounds S, Kang G, Shi L, Becksfort J, Gupta P, Payne-Turner D, Vadodaria B, Boggs K, Yergeau D, Manne J, Song G, Edmonson M, Nagahawatte P, Wei L, Cheng C, Pei D, Sutton R, Venn NC, Chetcuti A, Rush A, Catchpoole D, Heldrup J, Fioretos T, Lu C, Ding L, Pui C-H, Shurtleff S, Mullighan CG, Mardis ER, Wilson RK, Gruber TA*, Zhang J, Downing JR*. The landscape of somatic mutations in infant MLL rearranged acute lymphoblastic leukemias. Nat Genet 47:330-337, 2015. *co-corresponding authors
Huether R, Dong L, Easton J, Chen X, Wu G, Parker M, Wei L, Ma J, Edmonson MN, Hedlund EK, Rusch MC, Shurtleff SA, Vadordaria B, Yergeau D, Mulder HL, Song G, Becksfort J, Cheng J, Cai Z, Dang J, Walsh M, Gedman AL, Faber Z, Gruber TA, Kriwacki RW, Partridge JF, Ding L, Wilson RK, Mardis ER, Mullighan CG, Gilbertson RJ, Baker SJ, Zambetti G, Ellison DW, Zhang J, Downing JR. The landscape of somatic mutations in epigenetic regulators across 1000 pediatric cancer genomes. Nat Commun 5:3630, 2014.
Gruber TA, Gedman AL, Zhang J, Koss CS, Marada S, Ta H, Chen S-C, Su X, Ogden SK, Dang J, Gupta V, Andersson A, Pounds S, Shi L, Easton J, Barbato MI, Mulder HL, Manne J, Wang J, Rusch M, Ganti R, Ma J, Radtke I, Ding L, Cazzaniga G, Biondi A, Kornblau S, Ravandi-Kashani F, Kantarjian H, Nimer SD, Doehner K, Doehner H, Ley TJ, Ballerini P, Shurtleff S, Tomizawa D, Adachi S, Hayashi Y, Tawa A, Shih L-Y, Liang D-C, Rubnitz J, Pui C-H, Mardis ER, Wilson RK, Downing JR. An Inv(16)(p13.3q24.3)-encoded CBFA2T3-GLIS2 fusion protein defines an aggressive subtype of pediatric acute megakaryoblastic leukemia. Cancer Cell 22:683-697, 2012.
Last update: June 2017