Kathrin M. Bernt, MD

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Assistant Professor of Pediatrics
Department: Pediatrics
Graduate Group Affiliations

Contact information
3501 Civic Center Boulevard
CTRB Room 3064
Philadelphia, PA 19104
Office: 617-990-4925
MD (Pediatric Hematology/Oncology; MD thesis: summa cum laude. Thesis Advisor: Dr. W. Reutter)
Humboldt University Berlin/Free University Berlin, Germany, 1998.
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Description of Clinical Expertise

Care of patients with Pediatric Hematologic Malignancies at the Children's Hospital of Philadelphia (CHOP).

Description of Research Expertise

The goal: Understand the “molecular makeup” of leukemia to develop targeted therapies.Focus on epigenetics and transcription.

The Bernt lab is researching molecular mechanisms in leukemia, utilizing a wide range of models, including
- Genetically engineered murine models for common leukemogenic drivers (gain of function and loss of function): Inv(16), FLT3-ITD, mIDH2, CDKN2A-, EZH2-, EED1, GATA2-
- Retroviral murine models: MLL-AF9, MLL-AF6, MLL-ENL, AML-ETO, MN1, oncogenic NRAS, mIDH1, mIDH2
- Cell lines
- Patient samples and patient derived xenografts.

We study epigenetic and transcriptional regulation in leukemia with the goal of uncovering molecular mechanisms and developing new therapies and combinations.

Examples of projects:
- IDH mutations occur in 15% of adult AML. These mutations are mutually exclusive with inactivating mutations of the TET2 enzyme, which convers DNA methylcytosin to hydroxymethylcytosin. The canonical mechanism of mutant IDH induced leukemogenesis involved the production of massively increased levels of the “oncometabolite” 2HG which inhibits TET2 enzymatic function. However, 2HG also inhibits a number of histone demethylases. Data from our lab suggests that this chromatin pathway may be functionally relevant. We use retroviral and knock-in murine models with different co-drivers and patient samples to investigate the role of aberrant histone methylation in IDH-mutant AML. Funded by the NCI (R01)
- Meningioma-1 (MN1) is a poorly characterized transcriptional co-activator that serves as a fusion partner in MN1-TEL and MN1-FLI1 fusions in AML. It is also commonly overexpressed in AML. MN1 fusions as well as wild type MN1 are strongly oncogenic, however, the mechanism of leukemogenesis is poorly understood. We are using a broad approach involving syngeneic murine models, cell lines and patient samples as well as genomic/epigenomic/transcriptomic and proteomic approaches to uncover the molecular mechanism by which fusions and wild type MN1 cause leukemia, with the hope of identifying targeted therapeutic agents. Supported by the Doris Duke Charitable Foundation
- Inv(16) are found fairly frequently in children and adults with AML. Although considered a “good risk subtype”, almost 30% of children and 50% of adults still relapse, suggesting a need for improved therapeutic approaches. 100% of inv(16) AML overexpress MN1. We are studying the role of MN1, as well as additional epigenetic abnormalities in inv(16) AML using a genetic knock-in mouse model, cell lines and patient samples. Supported by Hyundai Hope on Wheels.
- Several ongoing smaller projects involving the oncogenes/pathways listed above.

Current Lab Members:
Simone Riedel, PhD, Senior Post-Doc
Clara Libbrecht, MD, Post-doctoral Fellow
Zhuo-Fei Yuan, PhD, Bioinformatics Scientist
Molly Kingsley, BS, Molecular Biology Graduate Student (UC Denver)
Taylor Pastuer, BA, lab manager/technician

Selected Publications

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 (EPZ-5676) Treatment-Emergent Resistance in MLL-Rearranged Leukemia. Mol Cancer Ther. Apr 2017 Notes: doi:10.1158/1535-7163.MCT-16-0693.

Bernt KM.: Bridging the Gaps: iPSC-Based Models from CHIP to MDS to AML. Cell Stem Cell. Mar 2017 Notes: doi: 10.1016/j.stem.2017.02.011.

Winters, Amanda C., Bernt, Kathrin M.: MLL-Rearranged Leukemias—An Update on Science and Clinical Approaches. Frontiers in Pediatrics 5: 4, 2017.

Haladyna Jessica N, Pastuer Taylor, Riedel Simone S, Perraud Anne-Laure, Bernt Kathrin M: Transient potential receptor melastatin-2 (Trpm2) does not influence murine MLL-AF9-driven AML leukemogenesis or in vitro response to chemotherapy. Experimental hematology 44(7): 596-602.e3, Jul 2016.

Bernt Kathrin M, Hunger Stephen P, Neff Tobias: The Functional Role of PRC2 in Early T-cell Precursor Acute Lymphoblastic Leukemia (ETP-ALL) - Mechanisms and Opportunities. Frontiers in pediatrics 4: 49, May 2016.

Bernt Kathrin M, Hunger Stephen P, Neff Tobias: The Functional Role of PRC2 in Early T-cell Precursor Acute Lymphoblastic Leukemia (ETP-ALL) - Mechanisms and Opportunities. Frontiers in pediatrics Frontiers in pediatrics 4(49), May 2016.

Riedel Simone S, Haladyna Jessica N, Bezzant Matthew, Stevens Brett, Pollyea Daniel A, Sinha Amit U, Armstrong Scott A, Wei Qi, Pollock Roy M, Daigle Scott R, Jordan Craig T, Ernst Patricia, Neff Tobias, Bernt Kathrin M: MLL1 and DOT1L cooperate with meningioma-1 to induce acute myeloid leukemia. The Journal of clinical investigation 126(4): 1438-50, Apr 2016 Notes: Highlight article in the print issue.

2.Bernt KM and Neff T: The role of Polycomb Repressive Complex 2 in Early T-Cell Precursor Acute Lymphoblastic Leukemia – Author’s View. Accepted at: Molecular & Cellular Oncology April 2016.

Danis Etienne, Yamauchi Taylor, Echanique Kristen, Zhang Xi, Haladyna Jessica N, Riedel Simone S, Zhu Nan, Xie Huafeng, Orkin Stuart H, Armstrong Scott A, Bernt Kathrin M, Neff Tobias: Ezh2 Controls an Early Hematopoietic Program and Growth and Survival Signaling in Early T Cell Precursor Acute Lymphoblastic Leukemia. Cell reports 14(8): 1953-65, Mar 2016.

Wolfe Schneider, K., Wei, Qi, Kuldanek, S., Bernt, KM.: Case example involving germline genetic counseling needs for 47,XXX, familial leukemia, and Noonan syndrome following somatic genetic testing. American Society of Pediatric Hematology Oncology (ASPHO) annual meeting, Minneapolis, MN - Poster Presentation 2016 Notes: Poster presentation.

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Last updated: 07/31/2018
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