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Kathrin M. Bernt, MD
Attending Physician
As a physician-scientist, Dr. Bernt's goal is to further the understanding of the role of transcriptional regulation in pediatric hematopoietic stem cell biology and leukemia, and translate findings into novel therapies.
Bio
Dr. Bernt aims to enhace the understanding of the role of transcriptional regulation in pediatric hematopoietic stem cell biology and leukemia, and translate findings into novel therapies. There is a growing appreciation that many different genetic alterations funnel into common transcriptional outcomes. Transcriptional alterations of developmental programs play a critical role in leukemogenesis and govern biological processes associated with relapse and refractory disease.
Dr. Bernt is using a combination of genetic conditional loss of function models for transcription factors, epigenetic modifiers, murine leukemia models, primary patient material, genome-wide expression, and epigenetic profiling at a bulk and single cell level, and small molecule inhibitors to dissect mechanisms of leukemogenesis and response to therapy.
Her current projects specifically involve investigating aberrant epigenetic and transcriptional mechanism in leukemia using a genetic murine model. This line of research inquiry includes projects on mutant IDH, Gata2, Meningeoma 1, KMT2D and Menin. In addition, Dr. Bernt is leading collaborating in large multi-omic studies on primary patient samples. These include histone profiling, bulk and single cell RNA-Seq, chromatin accessibility, ChIP-Seq, WGS of normal and leukemia bone marrow.
Her previous research accomplishment and contributions include:
- Translational work that lead to clinical trials investigating inhibition of the histone methyltransferase DOT1L for KMT2A rearranged leukemias
- Defining major mechanisms of resistance to DOT1L inhibition
- Identifying increased cytokine/JAK/STAT signaling as a consequence of loss of PRC2 in early T-cell precursor leukemia, suggesting JAK/STAT signaling inhibitors as potential therapeutic modalities
Education and Training
MD, Humbolt University, Berlin, Germany, 1998
Fellowship, University of Washington (Medical Genetics), 2003
Fellowship, Boston Children's Hospital (Pediatric Hematology and Oncology), 2009
Titles and Academic Titles
Attending Physician
Assistant Professor of Pediatrics
Professional Awards
Travel Award, Society of Hematology, 2000
Excellency in Research Award, Society of Gene Therapy, 2002
Travel Award, Society of Gene Therapy, 2002
SIOP Award Translational Research, International Society of Paediatric Oncology, 2010
ASCI Council's 2013 Young Physician-Scientist Awards, 2013
Publication Highlights
PubMed:
Campbell CT, Haladyna JN, Drubin DA, Thomson TM, Maria MJ, Yamauchi T, Waters NJ, Olhava EJ, Pollock RM, Smith JJ, Copeland RA, Blakemore SJ, Bernt KM, Daigle SR. Mechanisms of pinometostat (EPZ5676) emergent resistance in MLL-rearranged leukemias. Mol Cancer Ther. 2017 Aug; 16(8):1669-1679. PMID: 28428443
Riedel SS, Haladyna J, Bezzant M, Stevens B, Pollyea DA, Sinha AU, Armstrong SA, Wei Q, Pollock RM, Daigle SR, Jordan CT, Ernst P, Neff T, and Bernt KM. MLL1 and DOT1L cooperate with meningioma-1 to induce acute myeloid leukemia. J Clin Invest. 2016 Apr; 126(4):1438-50. PMID: 26927674
Danis E, Yamauchi T, Echanique K, Zhang X, Haladyna J, Riedel SS, Zhu N, Xie H, Orkin SH, Armstrong SA, Bernt KM and Neff T. Ezh2 controls an early hematopoietic program and growth and survival signaling in early T-Cell precursor acute lymphoblastic leukemia. Cell Rep. 2016 Mar; 14(8):1953-65. PMID 26904942
Daigle SR, Olhava EJ, Therkelsen CA, Majer CR, Sneering CJ, Song J, Johnston D, Porter Scott M, Smith JJ, Xiao Y, Jin L, Kuntz KW, Chesworth R, Moyer MP, Bernt KM, Armstrong SA, Copeland RA, Richon VM, Pollock RM. Selective killing of mixed lineage leukemia cells by a potent small-molecule DOT1L inhibitor. Cancer Cell. 2011 Jul; 20(1):53-65. PMCID: PMC4046888
Bernt KM, Zhu N, Sinha AU, Vempati S, Faber J, Krivtsov AV, Feng Z, Punt N, Daigle A, Bullinger L, Pollock R, Richon V, Kung AL, Armstrong SA. MLL-rearranged leukemia is dependent on aberrant H3K79 methylation by Dot1l. Cancer Cell. 2011 Jul; 20(1):66-78. PMCID: PMC3329803
Active Grants/Contracts
The role of H3K79 Methylation in IDH-mutant leukemia. NIH/NCI, December 2015-December 2020.This project is aimed at establishing the histone methyltransferase Dot1l as a therapeutic target in AML with IDH mutations, and at discovering the demethylase for H3K79 methylation. Role: PI
The Role of MN1 in inv(16) AML. Hyundai Hope on Wheels, January 2018-Deecmber 2019. This project will investigate the roles of DOT1L and MN1 in inv(16) AML. Role: PI
A single cell atlas of Childhood hematopoietic development. Emmerson Collective, August 2018-July 2020. Development of a single cell transcriptomic map of hematopoietic development in normal children. Role: PI
TOP2 Poisons: Old Drugs, New Mechanisms and Rational MLL-R AML Epigenetic Targeting Combinations. Leukemia and Lymphoma Society, July 2018-June 2021.This project is dedicated to interrogate interactions between topoisomerase inhibitors and H3K79 methylation in the context of leukemogenesis as well as individual or combined therapeutic targeting in KMT2A-rearranged leukemias.