Faculty

Kathrin M. Bernt, MD

faculty photo
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
Education:
MD (Pediatric Hematology/Oncology)
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

Lee S, Liu H, Hong X, Liu X, Crawford F, Zhang Q, Kingsley M, Chen Z, Lengeling A, Bernt K, Marrack P, Kappler J, Hansen K, Zhou Q, Li QY, Zhang G.: JMJD6 cleaves MePCE to Release pTEFb. eLife 2020; 9:e53930 PMID: 32048991 2020.

Taylor DM, Aronow BJ, Tan K, Bernt K, Salomonis N, Greene CS, Frolova A, Henrickson SE, Wells A, Pei L, Jaiswal JK, Whitsett J, Hamilton KE, MacParland SA, Kelsen J, Heuckeroth RO, Potter SS, Vella LA, Terry NA, Ghanem LR, Kennedy BC, Helbig I, Sullivan KE, Castelo-Soccio L, Kreigstein A, Herse F, Nawijn MC, Koppelman GH, Haendel M, Harris NL, Rokita JL, Zhang Y, Regev A, Rozenblatt-Rosen O, Rood JE, Tickle TL, Vento-Tormo R, Alimohamed S, Lek M, Mar JC, Loomes KM, Barrett DM, Uapinyoying P, Beggs AH, Agrawal PB, Chen YW, Muir AB, Garmire LX, Snapper SB, Nazarian J, Seeholzer SH, Fazelinia H, Singh LN, Faryabi RB, Raman P, Dawany N, Xie HM, Devkota B, Diskin SJ, Anderson SA, Rappaport EF, Peranteau W, Wikenheiser-Brokamp KA, Teichmann S, Wallace D, Peng T, Ding YY, Kim MS, Xing Y, Kong SW, Bönnemann CG, Mandl KD, White PS.: The Pediatric Cell Atlas: Defining the Growth Phase of Human Development at Single-Cell Resolution. Dev Cell 49(1): 10-29, Apr 2019.

Epigenetic regulation of protein translation in KMT2A-rearranged AML.: Lenard A, Xie HM, Riedel S, Yuan ZF, Zhu N, Neff T, Bernt KM. BioRxiv 2019 DOI: 10.1101/790287, http://biorxiv.org/cgi/content/short/790287v1 2019.

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 5(5): e1166309, May 2018.

Kingsley BS, Riedel SS, Xie HM, Stable SP, Pastuer T, Bernt KM: Tight regulation of H3K79 Methylation levels in KMT2A rearranged AML. American Society of Hematology (ASH) annual meeting, San Diego, CA 2018 Notes: poster presentation. Abstract achievement award.

Bernt Kathrin M, Neff Tobias: The role of polycomb repressive complex 2 in early T-cell precursor acute lymphoblastic leukemia. Molecular & cellular oncology 5(5): e1166309, 2018.

Libbrecht, C, Riedel SS, Haladyna BA, Bernt KM. H: Menin is a therapeutic target in MN1 high leukemia. American Society of Hematology (ASH) annual meeting, San Diego, CA 2018 Notes: oral presentation. Abstract achievement award.

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. 16(8): 1669-1679, Aug 2017.

Bernt KM.: Bridging the Gaps: iPSC-Based Models from CHIP to MDS to AML. Cell Stem Cell. 20(3): 298-299, March 2017.

Winters, Amanda C., Bernt, Kathrin M.: MLL-Rearranged Leukemias—An Update on Science and Clinical Approaches. Frontiers in Pediatrics 5(1): 4, February 2017.

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Last updated: 04/24/2020
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