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Daniel Savic, PhD
Daniel Savic, PhD


PhD – The University of Chicago, Chicago, Illinois (2012)

Research Interests

My primary research focus involves studying genome function and gene regulation in the context of pediatric leukemia in order to address a fundamental and critical question: how does the noncoding portion of the human genome impact chemotherapy response, chemotherapy resistance and relapse? The long-term goal of my research effort is to gain a better understanding of genome function, gene regulation and the underlying genetic factors impacting chemotherapeutic drug resistance and relapse in pediatric leukemia. Our laboratory is involved in three related areas of research:

  • Evaluating chromatin structure and the cis-regulatory landscape of acute lymphoblastic leukemia (ALL)
  • Mapping gene regulatory responses to chemotherapeutic drugs and alterations in response that impact drug resistance in ALL
  • Defining genetic and epigenetic alterations to cis-regulatory elements that impact chemotherapeutic drug resistance, treatment response and/or disease relapse in ALL

Selected Publications

Bhattarai KR, Mobley RJ, Barnett KR, Ferguson DC, Hansen BS, Diedrich JD, Bergeron BP, Yoshimura S, Yang W, Crews KR, Manring CS, Jabbour E, Paietta E, Litzow MR, Kornblau SM, Stock W, Inaba H, Jeha S, Pui CH, Cheng C, Pruett-Miller SM, Relling MV, Yang JJ, Evans WE and Savic D. Functional investigation of inherited noncoding variation impacting the pharmacogenomics of childhood acute lymphoblastic leukemia treatment. Nature Communications 2024;15(1):3681. Epub May 1, 2024. doi: 10.1038/s41467-024-48124-4. PubMed PMID: 38693155; PMCID: PMC11063049.

Barnett KR, Mobley, RJ, Diedrich JD, Bergeron BP, Bhattarai KR, Monovich AC, Narina S, Yang W, Crews KR, Manring CS, Jabbour E, Paietta E, Litzow MR, Kornblau SM, Stock W, Inaba H, Jeha S, Pui CH, Mullighan CG, Relling MV, Pruett-Miller SM, Ryan RJH, Yang JJ, Evans WE, Savic D. Epigenomic mapping reveals distinct B cell acute lymphoblastic leukemia chromatin architectures and regulators. Cell Genomics 2023.

Bergeron BP, Barnett KR, Mobley RJ, Hansen BS, Brown A, Kodali K, Jeha S, Pui CH, Peng J, Pruett-Miller SM and Savic D. Mutual antagonism between glucocorticoid and canonical Wnt signaling pathways in B-cell acute lymphoblastic leukemia. Blood Advances 2023. DOI: 10.1182/bloodadvances.2022009498. 

Zhao X, Wang P, Diedrich JD, Smart B, Reyes N, Yoshimura S, Zhang J, Yang W, Barnett K, Xu B, Li Z, Huang X, Yu J, Crews K, Yeoh AEJ, Konopleva M, Wei CL, Pui CH, Savic D, and Yang JJ. Epigenetic activation of the FLT3 gene by ZNF384 fusion confers a therapeutic susceptibility in acute lymphoblastic leukemia. Nature Communications. Sep 14, 2022;13(1):5401. doi:10.1038/s41467-022-33143-w.

Bergeron BP, Diedrich JD, Zhang Y, Barnett KR, Dong Q, Ferguson DC, Autry RJ, Yang W, Hansen BS, Smith C, Crews KR, Fan Y, Pui CH, Pruett-Miller SM, Relling MV, Yang JJ, Li C, Evans WE, Savic D. Epigenomic profiling of glucocorticoid responses identifies cis-regulatory disruptions impacting steroid resistance in childhood acute lymphoblastic leukemia. Leukemia 2022.

Zhao X, Qian M, Goodings C, Zhang Y, Yang W, Wang P, Beisi X, Tian C, Pui CH, Hunger SP, Raetz EA, Devidas M, Relling MV, Loh ML, Savic D, Li C, and Yang JJ. Molecular mechanisms of ARID5B-mediated susceptibility to acute lymphoblastic leukemia. J Natl Cancer Inst May 16:djac101, 2022. doi:10.1093/jnci/djac101. Epub ahead of print.

Ferguson DC, McCorkle JR, Barnett KR, Bonten EJ, Bergeron BP, Bhattarai KR, Yang W, Smith C, Hansen BS, Bajpai R, Dong Q, Autry RJ, Gocho Y, Diedrich JD, Crews KR, Qian M, Pruett-Miller SM, Roberts KG, Stock W, Mullighan CG, Inaba H, Jeha S, Pui CH, Yang JJ, Relling MV, Evans WE, Savic D. Amino acid stress response genes promote L-asparaginase resistance in pediatric acute lymphoblastic leukemia. Blood Advances. Jun 14, 2022;6(11):3386-3397. doi:10.1182/bloodadvances.2022006965

Diedrich JD, Dong Q, Ferguson DC, Bergeron BP, Autry RJ, Qian M, Yang W, Smith C, Papizan JB, Connelly JP, Hagiwara K, Crews KR, Pruett-Miller SM, Pui CH, Yang JJ, Relling MV, Evans WE and Savic D. Profiling chromatin accessibility in pediatric acute lymphoblastic leukemia identifies subtype-specific chromatin landscapes and gene regulatory networks. Leukemia 24 February, 2021.

Lee SH, Qian M, Yang W, Diedrich JD, Raetz E, Yang W, Dong Q, Devidas M, Pei D, Yeoh A, Cheng C, Pui CH, Evans WE, Mullighan CG, Hunger SP, Savic D, Relling MV, Loh M, Yang JJ. Genome-wide association study of susceptibility loci for TCF3-PBX1 acute lymphoblastic leukemia. J Natl Cancer Inst 3 Sept, 2020. doi:10.1093/jnci/djaa133

Partridge EC, Chhetri SB, Prokop JW, Ramaker RC, Jansen CS, Goh ST, Mackiewicz M, Newberry KM, Brandsmeier LA, Meadows SK, Messer CL,  Hardigan AA, Dean EC, Jian S, Savic D, Mortazavi A, Wold BJ, Myers RM, Mendenhall EM. Occupancy patterns of 208 chromatin-associated proteins in a single human cell type. Nature 583(7818):720-728, 2020.

ENCODE Project Consortium. Expanded encyclopedias of DNA elements in the human and mouse genomes. Nature 583(7818):699-710, 2020.

Autry RJ, Paugh SW, Carter R, Shi L, Liu J, Ferguson DC, Lau CE, Bonten EJ, Yang W, McCorkle JR, Beard JA, Panetta JC, Diedrich JD, Crews KR, Pei D, Coke CJ, Natarajan S, Khatamian A, Karol SE, Lopez-Lopez E, Diouf B, Smith C, Gocho Y, Hagiwara K, Roberts KG, Pounds S, Kornblau SM, Stock W, Paietta EM, Litzow MR, Inaba H, Mullighan CG, Jeha S, Pui CH, Cheng C, Savic D, Yu J, Gawad C, Relling MV, Yang JJ, Evans WE.  Integrative genomic analyses reveal mechanisms of glucocorticoid resistance in acute lymphoblastic leukemia. Nature Cancer 9(8):2918-2929, 2020. 

Slavish P, Chi L, Yun MK, Tsurkan L, Martinez N, Jonchere B, Chai S, Connelly M, Waddell B, Das S, Neale G, Li Z, Shadrick W, Olsen R, Freeman K, Low J, Price J, Young B, Bharatham N, Boyd V, Lee R, Morfouace M, Roussel M, Chen T, Savic D, Guy RK, White S, Shelat A, Potter P. Bromodomain-selective BETi are potent antitumor agents against MYC-driven pediatric cancer. Cancer Research canres.3934.2019. 10 Jul, 2020. doi:10.1158/0008-5472.CAN-19-3934

Ramaker RC*, Savic D*, Hardigan AA, Newberry K, Cooper GM, Myers RM, Cooper SJ.  A genome-wide interactome of DNA-associated proteins in the human liver. Genome Research Nov;27(11):1950-1960, 2017. *equal contributions

Agee JM, Varley KE, Gertz J, Savic D, Roberts BS, Bailey SK, Shevde LA, Ramaker R, Lasseigne BN, Kirby MK, Newberry K, Partridge EC, Oliver PG, Sexton KG, Grizzle WE, Forero A, Buchsbaum DJ, Myers RM.  Genomic regulation of invasion by STAT3 in triple negative breast cancer.  Oncotarget Jan 31;8(5):8226-8238, 2017. 

Savic D, Ramaker RC, Roberts BS, Burwell TC, Dean EC, Meadows SK, Cooper SJ, Garabedian MJ, Gertz J, Myers RM. Distinct gene regulatory programs define the inhibitory effects of liver X receptors and PPARG on cancer cell proliferation. Genome Medicine Jul 11;8(1):74, 2016.

Engel KL, Mackiewicz M, Hardigan AA, Myers RM, Savic D. Decoding transcriptional enhancers: Evolution from annotation to functional interpretation. Seminars in Cellular and Developmental Biology Sep;57:40-50, 2016.

Savic D, Roberts BS, Carleston JB, Partridge EC, White MA, Cohen BA, Cooper GM, Gertz J, Myers RM. Promoter-distal RNA polymerase II binding discriminates active from inactive CCAAT/enhancer-binding protein beta binding sites. Genome Research Dec;25(12):1791-800, 2015.

Savic D, Partridge EC, Newberry K, Smith S, Meadows S, Roberts BS, Mackiewicz M, Mendenhall E, Myers RM. CETCh-seq: CRISPR epitope tagging ChIP-seq of DNA-binding proteins. Genome Research Oct;25(10):1581-9,2015.

Paugh SW, Bonten EJ, Savic D, Ramsey LB, Thierfelder WE, Gurung P, Malireddi RKS, Actis M, Mayasundari A, Min J, Coss DR, Laudermilk LT, Panetta JC, McCorkle JR, Fan Y, Crews KR, Stocco G, Wilkinson MR, Ferreira AM, Cheng C, Yang W, Karol SE, Fernandez CA, Diouf B, Smith C, Hicks JK, Zanut A, Giordanengo A, Crona D, Bianchi JJ, Holmfeldt L, Mullighan CG, den Boer ML, Pieters R, Jeha S, Dunwell TL, Latif F, Bhojwani D, Carroll WL, Pui CH, Myers RM, Guy RK, Kanneganti TD, Relling MV, Evans WE. NALP3 inflammasome upregulation and CASP1 cleavage of the glucocorticoid receptor cause glucocorticoid resistance in leukemia cells. Nature Genetics Jun;47(6):607-14, 2015.

Savic D, Gertz J, Jain P, Copper GM, Myers RM. Mapping genome-wide transcription factor binding sites in frozen tissues. Epigenetics & Chromatin 6(1):30, 2013.

Gertz J, Savic D, Varley KE, Partridge EC, Safi A, Jain P, Cooper GM, Reddy TE, Crawford GE, Myers RM. Distinct properties of cell type-specific and shared transcription factor binding sites. Molecular Cell 52(1):25-36, 2013. Recommended by Faculty 1000.

Sakabe NJ**, Savic D**, Nobrega MA. Transcriptional enhancers in development and disease. Genome Biology 13(1):238, 2012. **equal contributions and corresponding authors

Last update: May 2024