Grants

GRANTS FUNDED

NIH (NCI) R01: 1R01CA209829
“Targeting CRLF2 and Ikaros Alterations to Reduce Health Disparities in Childhood Leukemia”
$600,000 (PSU)
Dovat (MPI), 15% effort
07/2016-06/2021

NIH (NCI) R01: 1R01CA213912
“Targeting CK2 oncogenic pathway to overcome drug resistance in high- risk leukemia”
$1,250,063
Dovat (PI), 15% effort
07/2017-06//2022

Hyundai Hope on Wheels Scholar Grant
“Novel Targeted Combination Therapy for High-Risk Acute Lymphoblastic Leukemia”
$250,000
Dovat (PI), 10% effort
07/2016-12/2018

Alex’s Lemonade Stand
“Targeted Combination Therapy to Sensitize High-Risk Acute Lymphoblastic Leukemia to Methotrexate via Restoration of Ikaros Tumor Suppression”
$250,000
Dovat (PI), 10% effort
09/2016-8/2018

Bear Necessities Pediatric Cancer Foundation
“Accelerated Anti-Cancer Drug Discovery for the High-Risk Childhood Leukemia”
$200,000
Dovat (PI), 10%
07/2016-8/2018

Major International (Regional) Joint Research Project, National Science Foundation of China
“Epigenetic regulation and restoring Ikaros functions in anti-oncogenesis of high-risk leukemia”
$10,000 (PSU)
Role: Co-Primary Investigator
07/2017-6/2018

NIH 5R01HL095120
“The Role of Zinc Finger Genes in Leukomogenesis”
Role: PI
07/2009-06/2015

Hyundai Hope on Wheels Scholar Grant Award
“Regulation of Tumor Suppression in Childhood Leukemia”
Role: PI
09/01/2012-07/2014

St. Baldrick’s Foundation
“Summer Fellowship Award”
Role: Mentor
06/2013-08/2013

St. Baldrick’s Foundation
“St Baldrick’s Fellowship Award (Steffans)”
Role: Mentor
5/2014-4/2015

St. Baldrick’s Foundation
“Summer Fellowship Award”
Role: Mentor
05/2015-04/2016

St. Baldrick’s Foundation
“Summer Fellowship Award”
Role: Mentor
05/2016-04/2017

CURRENT RESEARCH

Dr. Sinisa Dovat became Director of Translational Research in the Pediatric Experimental Therapeutics Program in 2010. The long-term goal of Dr. Dovat’s work is to understand how the loss of normal gene regulation leads to cancer in humans.

The most important difference between cancer cells compared to normal cells is in the way they divide and multiply. Cancer cells are immortal; they divide rapidly and they divide indefinitely.

The focus of Dr. Dovat’s internationally-recognized laboratory is to discover how abnormities in certain genes result in cancer, and is focused on several research projects. One of the projects he studies involves a gene called Ikaros, which is important in leukemia because it controls a number of other genes. When it is absent in patients’ cells, high-risk childhood leukemia can develop, which has a poor outcome.

Dr. Dovat’s lab wants to understand how Ikaros controls the growth of leukemia cells in order to design new drugs targeted to Ikaros to treat leukemia. Thus, research in the Dovat lab is translational, with an emphasis on understanding basic mechanisms of pediatric cancer in order to design of more effective therapeutic strategies and agents.

SELECTED PUBLICATIONS

The following are publications of Dr. Dovat’s lab sine 2012:

Nicolae CM, O’Connor MJ, Schleicher EM, Song C, Gowda R, Robertson G, Dovat S, Moldovan GL. PARI (PARPBP) suppresses replication stress-induced myeloid differentiation in leukemia cells. Oncogene. 2019 Apr 9. doi: 10.1038/s41388-019-0810-x. [Epub ahead of print] PMID: 30967629

Ge Z, Han Q, Gu Y, Ge Q, Ma J, Sloane J, Gao G, Payne KJ, Szekely L, Song C, Dovat S. Aberrant ARID5B expression and its association with Ikaros dysfunction in acute lymphoblastic leukemia. Oncogenesis. 2018 Nov 12;7(11):84. doi: 10.1038/s41389-018-0095-x. PMID:30420689

Tong YQ, Zhao ZJ, Liu B, Bao AY, Zheng HY, Gu J, Xia Y, McGrath M, Dovat S, Song CH, Li Y. New rapid method to detect BCR-ABL fusion genes with multiplex qRT-PCR in one-tube at a time. Leuk Res. 2018 Jun;69:47-53. doi: 10.1016/j.leukres.2018.04.001. Epub 2018 Apr 4. PMID: 29655153

Ge Z, Gu Y, Han Q, Sloane J, Ge Q, Gao G, Ma J, Song H, Hu J, Chen B, Dovat S, Song C. Plant homeodomain finger protein 2 as a novel IKAROS target in acute lymphoblastic leukemia. Epigenomics. Epigenomics. 2018 Jan;10(1):59-69. doi: 10.2217/epi-2017-0092. PMID: 28994305

Pandey MK, Gowda K, Sung SS, Abraham T, Budak-Alpdogan T, Talamo G, Dovat S, Amin S. A novel dual inhibitor of microtubule and Bruton’s tyrosine kinase inhibits survival of multiple myeloma and osteoclastogenesis. Exp Hematol. 2017 Jun 22. pii: S0301-472X(17)30233-3. doi: 10.1016/j.exphem.2017.06.003. [Epub ahead of print] PMID:28647392

Gowda C, Soliman M, Kapadia M, Ding Y, Payne K, Dovat S. Casein Kinase II (CK2), Glycogen Synthase Kinase-3 (GSK-3) and Ikaros mediated regulation of leukemia. Adv Biol Regul. 2017 Jun 13. pii: S2212-4926(17)30090-8. doi: 10.1016/j.jbior.2017.06.001. [Epub ahead of print] PMID:28623166

Dovat S, Payne KJ. STAT5 alters the state of transcriptional networks, driving aggressive leukemia. Nat Immunol. 2017 May 18;18(6):597-598. doi: 10.1038/ni.3747 PMID:28518152

Yoshida N, Sakaguchi H, Muramatsu H, Okuno Y, Song C, Dovat S, Shimada A, Ozeki M, Ohnishi H, Teramoto T, Fukao T, Kondo N, Takahashi Y, Matsumoto K, Kato K, Kojima S. Germline IKAROS mutation associated with primary immunodeficiency that progressed to T-cell acute lymphoblastic leukemia. Leukemia, 2017 Feb 3. doi: 10.1038/leu.2017.25. [Epub ahead of print] PMID:28096536

Ge Z, Zhou X, Gu Y, Han Q, Li J, Chen B, Ge Q, Dovat E, Payne JL, Sun T, Song C, Dovat S. Ikaros regulation of the BCL6/BACH2 axis and its clinical relevance in acute lymphoblastic leukemia. Oncotarget. 2017 Jan 31;8(5):8022-8034. doi: 10.18632/oncotarget.14038. PMID: 28030830

Ge Z, Gu Y, Han Q, Zhao G, Li M, Li J, Chen B, Sun T, Dovat S, Gale RP, Song C. Targeting high Dynamin-2 (DNM2) expression by restoring Ikaros function in acute lymphoblastic leukemia. Sci Rep. 2016 Nov 25;6:38004. doi: 10.1038/srep38004. PMID:27885263

Gowda C, Sachdev M, Muthisami S, Kapadia M, Petrovic-Dovat L, Hartman M, Ding Y, Song C, Payne JL, Tan BH, Dovat S. Casein Kinase II (CK2) as a therapeutic target for hematological malignancies. Curr Pharm Des. 2016 Oct 6. [Epub ahead of print]. PMID:27719640

Ge Z, Li M, Zhao G, Xiao L, Gu Y, Zhou X, Yu MD, Li J, Dovat S, Song C. Novel Dynamin 2 mutations in adult T-cell acute lymphoblastic leukemia. Oncol Lett. 2016 Oct;12(4):2746-2751. PMID: 27698851

Bao L, Chen SJ, Conrad K, Keefer K, Abraham T, Lee JP, Wang J, Zhang XQ, Hirschler-Laszkiewicz I, Wang HG, Dovat S, Gans B, Madesh M, Cheung JY, Miller BA. Depletion of the human ion channel TRPM2 in Neuroblastoma demonstrates its key role in cell survival through modulation of mitochondrial reactive oxygen species and bioenergetics. J Biol Chem. 2016 Nov 18;291(47):24449-24464. PMID: 27694440

Gowda C, Song C, Kapadia M, Payne JL, Hu T, Ding Y, Dovat S. Regulation of cellular proliferation in acute lymphoblastic leukemia by Casein Kinase II (CK2) and Ikaros. Adv Biol Regul. 2016 Sep 18. pii: S2212-4926(16)30039-2. doi: 10.1016/j.jbior.2016.09.003. [Epub ahead of print]. PMID: 27666503

Ge Z, Gu Y, Zhao G, Li J, Chen B, Han Q, Guo X, Liu J, Li H, Yu MD, Olson J, Steffens S, Payne KJ, Song C, Dovat S. High CRLF2 expression associates with IKZF1 dysfunction in adult acute lymphoblastic leukemia without CRLF2 rearrangement. Oncotarget. 2016 Aug 2;7(31):49722-49732. doi: 10.18632/oncotarget.10437. PMID: 27391346

Milford TM, Su RJ, Francis OL, Baez I, Martinez SR, Coats JS, Weldon AJ, Calderon MN, Nwosu MC, Botimer AR, Suterwala BT, Zhang XB, Morris CL, Weldon DJ, Dovat S, Payne KJ. TSLP or IL-7 provide an IL-7Rα signal that is critical for human B lymphopoiesis. Eur J Immunol. 2016 Sep;46(9):2155-61. doi: 10.1002/eji.201646307. PMID: 27325567

Ge Z, Gu Y, Xiao L, Han Q, Li J, Chen B, Yu J, Kawasawa YI, Payne KJ, Dovat S*, Song C*. Co-existence of IL7R high and SH2B3 low expression distinguishes a novel high-risk acute lymphoblastic leukemia with Ikaros dysfunction. Oncotarget. 2016 Jul 19;7(29):46014-46027. doi: 10.18632/oncotarget.10014. PMID: 27322554 *Corresponding authors

Ge Z, Song EJ, Kawasawa YI, Li J, Dovat S*, and Song C*. WDR5 high expression and its effect on tumorigenesis in Leukemia. Oncotarget. 2016 Jun 21;7(25):37740-37754. doi: 10.18632/oncotarget.9312. *Corresponding authors

Xiang M, Su H, Shu G, Wan D, He F, Loaec M, Ding Y, Li J, Dovat S, Yang G, Song C. Amplexicaule A exerts anti-tumor effects by inducing apoptosis in human breast cancer. Oncotarget. 2016 Apr 5;7(14):18521-30. doi: 10.18632/oncotarget.7848. PMID: 26943775

Gowda CS, Song C, Ding Y, Kapadia M, Dovat S. Protein signaling and regulation of gene transcription in leukemia: role of Casein Kinase II-Ikaros axis. J Investig Med. 2016 Mar;64(3):735-9. doi: 10.1136/jim-2016-000075. Epub 2016 Feb 9. PMID: 26912004

Wang H, Song C, Ding Y, Pan X, Ge Z, Tan BH, Gowda C, Sachdev M, Muthusami S, Ouyang H, Lai L, Francis OL, Morris CL, Abdel-Azim H, Dorsam G, Xiang M, Payne KJ, Dovat S. Transcriptional regulation of JARID1B/KDM5B histone demethylase by Ikaros, Histone deacetylase 1 (HDAC1) and Casein kinase 2 (CK2) in B cell acute lymphoblastic leukemia. J Biol Chem. 2016 Feb 19;291(8):4004-18. doi: 10.1074/jbc.M115.679332. Epub 2015 Dec 10. PMID: 26655717

Song C, Pan X, Ge Z, Gowda C, Ding Y, Li H, Li Z, Yochum G, Muschen M, Li Q, Payne KJ, Dovat S. Epigenetic regulation of gene expression by Ikaros, HDAC1 and Casein Kinase II (CK2) in leukemia. Leukemia 2016. 30, 1436–1440; doi:10.1038/leu.2015.331

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, 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. doi: 10.1182/blood-2015-06-651505. PMID: 26219304
Editorial highlight in Inside Blood: Blood 2015 126: 1735-1736. doi:10.1182/blood-2015-08-662544

Ge Z, Guo X, Li J, Hartman M, Kawasawa YI, Dovat S.* and Song C.* Clinical Significance of high c-MYC and low MYCBP2 expression and their association with Ikaros dysfunction in adult acute lymphoblastic leukemia. Oncotarget. 2015 Dec 8;6(39):42300-11. doi: 10.18632/oncotarget.5982. [Epub ahead of print] PMID: 26517351 *Corresponding authors.

Francis OL, Milford TM, Martinez SR, Baez I, Coats JS, Mayagoitia K, Concepcion KR, Ginelli E, Beldiman C, Benitez A, Weldon AJ, Arogyaswamy K, Shiraz P, Fisher R, Morris CL, Zhang XB, Filippov V, Van Handel B, Ge Z, Song C, Dovat S, Su RJ, Payne KJ. A novel xenograft model to study the role of TSLP-induced CRLF2 signals in normal and malignant human B lymphopoiesis. Haematologica. 2015 Nov 26. pii: haematol.2015.125336. [Epub ahead of print]. PMID: 26611474

Payne KJ, Benitez A, Dovat S. Translating Basic Science Discoveries to clinical practice-Let us not repeat the naivete of the pre-omics era. Ann Transl Med. 2015 Mar;3(4):46. doi: 10.3978/j.issn.2305-5839.2015.01.39. PMID: 25861601

Hu RM, Tan BH, Tester DJ, Song C, He Y, Dovat S, Peterson BZ, Ackerman MJ, Makielski JC. Arrhythmogenic biophysical phenotype for SCN5A mutation S1787N depends upon splice variant background and intracellular acidosis. PLoS One. 2015 Apr 29;10(4):e0124921. doi: 10.1371/journal.pone.0124921. eCollection 2015. PMID: 25923670

Guo X, Zhang R, Liu J, Li M, Song C, Dovat S, Li J, Ge Z. Characterization of LEF1 high expression and Novel mutations in adult acute lymphoblastic leukemia. PLoS One. May 5;10(5):e0125429, 2015. doi: 10.1371/journal.pone.0125429. eCollection 2015. PMID:25942645

Wang H, Song C, Gurel Z, Song N, Ma J, Ouyang H, Lai L, Payne KJ, Dovat S. Protein Phosphatase 1 (PP1) and Casein Kinase II (CK2) regulate Ikaros-mediated repression of TdT in thymocytes and T-cell leukemia. Pediatr Blood Cancer. 11, 2014. doi: 10.1002/pbc.25221.

Pandey, Manoj K., Vijay P. Kale, Chunhua Song, Shen-shu Sung, Arun K. Sharma, Giampaolo Talamo, Sinisa Dovat, and Shantu G. Amin. “Gambogic acid inhibits multiple myeloma mediated osteoclastogenesis through suppression of chemokine receptor CXCR4 signaling pathways”. Experimental Hematology 42, 10: 883-896, 2014. doi:10.1016/j.exphem.2014.07.261

Iempridee T, Reusch JA, Riching A, Johannsen EC, Dovat S, Kenney SC, Mertz JE. Epstein-Barr Virus Utilized Ikaros in regulating its latent-lytic switch in B cells. J Virol.88(9):4811-27, 2014. PMID: 24522918

Wang H, Ouyang H, Lai L, Petrovic-Dovat L, Stankov K, Bogdanovic G, Dovat S. Pathogenesis and regulation of cellular proliferation in acute lymphoblastic leukemia – the role of Ikaros. J BUON. 19(1):22-8, 2014. PMID: 24659638

Gowda C, Dovat S. Genetic targets in pediatric acute lymphoblastic leukemia. Adv Exp Med Biol. 779:327-40, 2013. doi: 10.1007/978-1-4614-6176-0_15. PMID:23288647

Yang D, Song J, Wu L, Ma Y, Song C, Dovat S, Nishizaki T, Liu J. Induction of senescence by adenosine suppressing the growth of lung cancer cells. Biochem Biophys Res Commun. 11;440(1):62-7, 2013.doi: 10.1016/j.bbrc.2013.09.030. PMID: 24051088

Dovat S. Ikaros: The enhancer makes the difference. Blood. 122(18):3091-2, 2013. doi: 10.1182/blood-2013-09-526343. PMID:24178958.

Payne KJ, Dovat S. G0S2-A new player in leukemia. Leuk Res. 38 (2): 147, 2013, i:S0145-2126(13)00412-8.doi: 10.1016/j.leukres.2013.11.011. PMID:24332429

Savic A., Cemerikic-Martinovic V., Dovat S., Rajic N., Urosevic I., Sekulic B., Kvrgic V., Popovic S. Angiogenesis and Survival in Patients with Myelodysplastic Syndrome. Pathol Oncol Res, 18(3):681-90, 2012.

Li Z., Song C., Ouyang H., Lai L., Payne K., Dovat S. Cell Cycle-Specific Function of Ikaros in Human Leukemia. Pediatr Blood Cancer, 59(1):69-76, 2012.

Uckun FM, Ma H, Zhang J, Ozer Z, Dovat S, Mao C, Ishkhanian R, Goodman P, Qazi S. Serine phosphorylation by SYK is critical for nuclear localization and transcription factor function of Ikaros. Proc Natl Acad Sci U S A. 109(44):18072-7, 2012.

Sinisa Dovat, M.D., Ph.D.