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

Riedel SS, Lu CC, Xie HM, Nestler K, Lenard A, Vermunt MW, Bennet L., Speck NA, Hanamura I, Lessard J, Blobel GA, Garcia BA and Bernt KM: Intrinsically disordered Meningioma-1 stabilizes the BAF complex to cause AML. Mol Cell . 3(S1097-2765(21)): 00319-1, May 2021 Notes: DOI: 10.1016/j.molcel.2021.04.014.

Libbrecht C, Xie H, Kingsley MC, Haladyna J, Riedel SS, Alikarami F, Lenard A, McGeehan G, Ernst P, and Bernt KM: Menin is necessary for long term maintenance of meningioma-1 driven leukemia. Leukemia 35(5): 1405-1417, May 2021.

Diorio C, Henrickson SE, Vella LA, McNerney KO, Chase JM, Burudpakdee C, Lee JH, Jasen C, Balamuth F, Barrett DM, Banwell B, Bernt KM, Blatz AM, Chiotos K, Fisher BT, Fitzgerald JC, Gerber JS, Gollomp K, Gray C, Grupp SA, Harris RM, Kilbaugh TJ, Odom John AR, Lambert MP, Liebling EJ, Paessler M, Petrosa W, Phillips CA, Reilly AF, Romberg N, Seif AE, Sesok-Pizzini D, Sullivan K, Vardaro J, Behrens EM, Teachey DT, Bassiri H: Multisystem inflammatory syndrome in children and COVID-19 are distinct presentations of SARS-CoV-2. J Clin Invest 130(11): 5967-5975, November 2020 Notes: DOI: 10.1172/JCI140970.

Kingsley MC, Xie HM, Riedel SS, Pastuer T, Shank T, Bollig M, Stabler S, Libbrecht C, Deshpande A, Intlekofer A, Bernt KM: Specific patterns of H3K79 methylation influence genetic interaction of oncogenes in AML. Blood Advances 4(13): 3109–3122, July 2020 Notes: doi: 10.1182/bloodadvances.2020001922.

Lenard A, Xie HM, Riedel S, Yuan ZF, Zhu N, Neff T, Bernt KM: Epigenetic regulation of protein translation in KMT2A-rearranged AML. Exp Hematology 85: 57-69, May 2020 Notes: DOI: 10.1016/j.exphem.2020.04.007.

Rozenblatt-Rosen O, Regev A, Oberdoerffer P, Williams EH; Human Tumor Atlas Network (extended author list: Bernt K). : The Human Tumor Atlas Network: Charting Tumor Transitions across Space and Time at Single-Cell Resolution. Cell 181(2): 236-249, April 2020 Notes: DOI: 10.1016/j.cell.2020.03.053.

Chen C, Yu W, Alikarami F, Qiu Q, Chen C, Flournoy J, Gao P, Uzun Y, Fang L, Hu Y, Zhu Q, Wang K, Libbrecht C, Felmeister A, Rosich I, Ding Y, Hunger SP, Wu H, Brown P, Guest E, Barrett D, Bernt KM, Tan K: Single-cell multi-omics reveals elevated plasticity and stem-cell-like blasts relevant to the poor prognosis of KMT2A-rearranged leukemia. BioRx 2020 Notes: https://doi.org/10.1101/2020.12.06.413930.

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 12(9): e53930, February 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.

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.

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Last updated: 05/17/2021
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