Research Seminar: “Global Epigenetic Regulation of Tumor Suppression and Targeted Treatment for Pediatric Leukemia”
Sinisa Dovat, MD, PhD
Professor, Department of Pediatrics, Biochemistry and Molecular Biology, and Pharmacology
Vice Chair for Basic Science Research, Department of Pediatrics
Four Diamonds Endowed Chair, Pediatric Hematology/Oncology
Pennsylvania State University, College of Medicine,
Milton S. Hershey Medical Center, Children’s Hospital
Ikaros (IKZF1) functions as a master regulator of hematopoiesis and a tumor suppressor. Impaired Ikaros function results in the development of high-risk leukemia. Ikaros directly regulates transcription of its target genes, as well as the global epigenetic landscape in leukemia. In vivo, Ikaros is a target for CK2, a pro-oncogenic kinase. CK2 directly phosphorylates Ikaros at multiple amino acids. Functional experiments showed that CK2-mediated phosphorylation of Ikaros regulates Ikaros' DNA binding affinity, and its tumor suppressor function. Inhibition of CK2 restores Ikaros function in epigenetic regulation of gene expression and results in therapeutic effect in pre-clinical leukemia models.
About the Speaker
Dr. Dovat completed his clinical training at Pennsylvania State University, and at UCLA-Children’s Hospital. He received his research training at Cornell University and at Howard Hughes Medical Institute at UCLA. Dr. Dovat is the recipient of The Young Investigator Award by The American Society of Pediatric Hematology/Oncology and has been included in the Best Doctors in America list. Dr. Dovat is the Four Diamond Endowed Chair and Director of Translational Research and Developmental Therapeutics in Pediatric Hematology/Oncology at Pennsylvania State University College of Medicine. Dr. Dovat’s research interests include epigenomic regulation of gene expression and developmental therapy for malignant diseases.
Gordana Raca, MD, PhD, FACMG
Director, Clinical Cytogenomics Laboratory
Center for Personalized Medicine (CPM)
Department of Pathology and Lab Medicine
Children’s Hospital Los Angeles
Associate Professor of Clinical Pathology
Keck School of Medicine of USC
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