522 First Avenue
New York, NY 10016
Our laboratory is focused on two major challenges facing children with acute lymphoblastic leukemia (ALL).
First, in spite of dramatic improvements in outcome one in four children will suffer a relapse and their prognosis is poor.
Second, the "cost" of therapy for those who are cured is high with short and long term side effects. Therefore our laboratory seeks to understand mechanisms of drug resistance and to identify pathways unique to the cancer cell that can serve as targets for more effective, less toxic therapeutic approaches.
In addition we are using genomic and proteomic approaches to predict prognosis better so that therapy can be tailored to the individual patient thereby maximizing chances for cure while minimizing side effects.
We have identified gene expression profiles that predict response to therapy and are validating these signatures in an independent cohort of children currently undergoing therapy for ALL.
In addition similar efforts using expression profiling to characterize blasts at relapse has led to the provisional identification of a number of drug resistance mechanisms in ALL.
We are now using siRNA approaches to validate the functional significance of these pathways and our long term goal is to use relevant pathways as targets for therapy.
Finally we have had a long term interest in defining cell death pathways that operate in vivo and have discovered that leukemic blasts use a variety of pathways to execute apoptosis.
We hypothesize that the route of cell death correlates with response to therapy and such pathways can be modulated to favor cancer cell death thereby maximizing the therapeutic potential of conventional agents.
Our laboratory encompasses the full spectrum of investigation involving basic "bench" research, highly translational efforts using samples from patients and clinical trials in children with ALL.
Intensified chemotherapy without SCT in infant ALL: Results from COG P9407 (Cohort 3)
Dreyer, ZoAnn E; Hilden, Joanne M; Jones, Tamekia L; Devidas, Meenakshi; Winick, Naomi J; Willman, Cheryl L; Harvey, Richard C; Chen, I-Ming; Behm, Fred G; Pullen, Jeanette; Wood, Brent L; Carroll, Andrew J; Heerema, Nyla A; Felix, Carolyn A; Robinson, Blaine; Reaman, Gregory H; Salzer, Wanda L; Hunger, Stephen P; Carroll, William L; Camitta, Bruce M
2015-03-06; 1545-5009,Pediatric blood & cancer - id: 1477622, year: 2015 Journal Article
Genome-wide analysis links NFATC2 with asparaginase hypersensitivity
Fernandez, Christian A; Smith, Colton; Yang, Wenjian; Mullighan, Charles G; Qu, Chunxu; Larsen, Eric; Bowman, W Paul; Liu, Chengcheng; Ramsey, Laura B; Chang, Tamara; Karol, Seth E; Loh, Mignon L; Raetz, Elizabeth A; Winick, Naomi J; Hunger, Stephen P; Carroll, William L; Jeha, Sima; Pui, Ching-Hon; Evans, William E; Devidas, Meenakshi; Relling, Mary V
2015-05-24; 1528-0020,Blood - id: 1590842, year: 2015 JOURNAL ARTICLE
Rise and fall of subclones from diagnosis to relapse in pediatric B-acute lymphoblastic leukaemia
Ma, Xiaotu; Edmonson, Michael; Yergeau, Donald; Muzny, Donna M; Hampton, Oliver A; Rusch, Michael; Song, Guangchun; Easton, John; Harvey, Richard C; Wheeler, David A; Ma, Jing; Doddapaneni, HarshaVardhan; Vadodaria, Bhavin; Wu, Gang; Nagahawatte, Panduka; Carroll, William L; Chen, I-Ming; Gastier-Foster, Julie M; Relling, Mary V; Smith, Malcolm A; Devidas, Meenakshi; Guidry Auvil, Jaime M; Downing, James R; Loh, Mignon L; Willman, Cheryl L; Gerhard, Daniela S; Mullighan, Charles G; Hunger, Stephen P; Zhang, Jinghui
2015-04-06; 2041-1723,Nature communications - id: 1520792, year: 2015 Journal Article
NALP3 inflammasome upregulation and CASP1 cleavage of the glucocorticoid receptor cause glucocorticoid resistance in leukemia cells
Paugh, Steven W; Bonten, Erik J; Savic, Daniel; Ramsey, Laura B; Thierfelder, William E; Gurung, Prajwal; Malireddi, R K Subbarao; Actis, Marcelo; Mayasundari, Anand; Min, Jaeki; Coss, David R; Laudermilk, Lucas T; Panetta, John C; McCorkle, J Robert; Fan, Yiping; Crews, Kristine R; Stocco, Gabriele; Wilkinson, Mark R; Ferreira, Antonio M; Cheng, Cheng; Yang, Wenjian; Karol, Seth E; Fernandez, Christian A; Diouf, Barthelemy; Smith, Colton; Hicks, J Kevin; Zanut, Alessandra; Giordanengo, Audrey; Crona, Daniel; Bianchi, Joy J; Holmfeldt, Linda; Mullighan, Charles G; den Boer, Monique L; Pieters, Rob; Jeha, Sima; Dunwell, Thomas L; Latif, Farida; Bhojwani, Deepa; Carroll, William L; Pui, Ching-Hon; Myers, Richard M; Guy, R Kiplin; Kanneganti, Thirumala-Devi; Relling, Mary V; Evans, William E
2015-05-11; 1546-1718,Nature genetics - id: 1569082, year: 2015 JOURNAL ARTICLE
Re-induction chemoimmunotherapy with epratuzumab in relapsed acute lymphoblastic leukemia (ALL): Phase II results from Children's Oncology Group (COG) study ADVL04P2
Raetz, Elizabeth A; Cairo, Mitchell S; Borowitz, Michael J; Lu, Xiaomin; Devidas, Meenakshi; Reid, Joel M; Goldenberg, David M; Wegener, William A; Zeng, Hui; Whitlock, James A; Adamson, Peter C; Hunger, Stephen P; Carroll, William L
2015-03-08; 1545-5009,Pediatric blood & cancer - id: 1480422, year: 2015 JOURNAL ARTICLE