Kun Zhu, Ph.D.

faculty photo
Research Associate of Medicine (Endocrinology, Diabetes and Metabolism)
Research Associate, University of Pennsylvania
Department: Medicine

Contact information
3400 Civic Center Blvd
SCTR building 12-192
Philadelphia, PA 19104
Office: 3018755363
Education:
B.S.
Wuhan University, 2010.
Ph.D.
Wuhan University, 2015.
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Description of Research Expertise

I am a Research Associate in Mitchell Lazar’s lab in the Department of Medicine at the University of Pennsylvania, with more than 10 years of experience studying how genetic and environmental factors interact to drive metabolic disease. My primary expertise lies in understanding how epigenetic and 3D genome–mediated mechanisms control circadian rhythms and metabolic homeostasis. I have extensive experience utilizing in vivo rodent models and high-throughput genomic and epigenomic approaches to investigate how epigenetic modifiers regulate transcription in response to different signaling pathways (Zhu et al., Nucleic Acids Res. 2017; Wang and Zhu et al., J Cell Sci. 2012) and how nuclear receptor PPAR influences fatty liver disease (Zhu et al., PLoS Biol. 2018). Recently, my research on hepatic nuclear receptors and clock components has deepened our understanding of the role of circadian rhythms and 3D genome-mediated transcription in liver physiology, advancing this field into new dimensions (Zhu et al., Mol Cell. 2023).

My developing research program integrates cutting-edge functional genomics, AAV-based genetic perturbation, and neural circuit tracing to elucidate how circadian clocks and nuclear receptors regulate circadian food intake. I previously pioneered in vivo manipulation of hepatic genes and circadian rhythms using AAV-delivered CRISPR/Cas9 and shRNA systems (Zhu et al., Mol Cell. 2023). Building on this foundation, I have expanded this AAV-based CRISPR perturbation platform (“AAV-Perturb”) to multiple metabolic tissues, enabling large-scale loss-of-function genetic studies in vivo.

Selected Publications

Tackenberg MC, Heliodoro KM, Melink LC, Liu Y, Zhu K, Lazar MA.: Normal circadian period length requires repression of Npas2 by REV-ERB nuclear receptors. Cell Rep Oct 2025.

Zhou D, Chen Y, Liu P, Zhu K, Holder-Haynes J, Lloyd SJ, La CM, Astapova II, Choa S, Xiong Y, Bae H, Aguilar M, Yang H, An YA, Sun Z, Herman MA, Gao X, Pei L, Jang C, Rabinowitz JD, Mattar SG, Zhang Y, Guan D.: Genetics-nutrition interactions control diurnal enhancer-promoter dynamics and liver lipid metabolism. Cell Metab Oct 2025.

Hauck AK, Mehmood R, Carpenter BJ, Frankfurter MT, Tackenberg MC, Inoue SI, Krieg MK, Cassim Bawa FN, Midha MK, Zundell DM, Batmanov K, Lazar MA.: Nuclear Receptor Corepressors Non-Canonically Drive Glucocorticoid Receptor-Dependent Activation of Hepatic Gluconeogenesis. Nat Metab May 2024.

Zhu K, Celwyn IJ, Guan D, Xiao Y, Wang X, Hu W, Jiang C, Cheng L, Casellas R, Lazar MA.: An intrinsically disordered region controlling condensation of a circadian clock component and rhythmic transcription in the liver. Mol Cell 83: 3457-3469, Oct 2023.

Guan D, Bae H, Zhou D, Chen Y, Jiang C, La CM, Xiao Y, Zhu K, Hu W, Trinh TM, Liu P, Xiong Y, Cai B, Jang C, Lazar MA.: Hepatocyte SREBP signaling mediates clock communication within the liver. J Clin Invest 133: e163018, Apr 2023.

Xiao Y, Batmanov K, Hu W, Zhu K, Tom AY, Guan D, Jiang C, Cheng L, McCright SJ, Yang EC, Lanza MR, Liu Y, Hill DA, Lazar MA.: Hepatocytes demarcated by EphB2 contribute to the progression of nonalcoholic steatohepatitis. Sci Transl Med 15: eadc9653, Feb 2023.

Chen Y, Chen S, Lei EP.: DiffChIPL: a differential peak analysis method for high-throughput sequencing data with biological replicates based on limma. Bioinformatics Sep 2022.

Hu W, Jiang C, Kim M, Xiao Y, Richter HJ, Guan D, Zhu K, Krusen BM, Roberts AN, Miller J, Steger DJ, Lazar MA.: Isoform-specific functions of PPARγ in gene regulation and metabolism. Genes Dev 36: 300-312, Mar 2022.

Dierickx P, Zhu K, Carpenter BJ, Jiang C, Vermunt MW, Xiao Y, Luongo TS, Yamamoto T, Martí-Pàmies Í, Mia S, Latimer M, Diwan A, Zhao J, Hauck AK, Krusen B, Nguyen HCB, Blobel GA, Kelly DP, Pei L, Baur JA, Young ME, Lazar MA.: Circadian REV-ERBs repress E4bp4 to activate NAMPT-dependent NAD(+) biosynthesis and sustain cardiac function. Nat Cardiovasc Res Jan 2022.

Hu W, Jiang C, Kim M, Yang W, Zhu K, Guan D, Lv W, Xiao Y, Wilson JR, Rader DJ, Pui CH, Relling MV, Lazar MA.: Individual-specific functional epigenomics reveals genetic determinants of adverse metabolic effects of glucocorticoids. Cell Metab 33: 1592-1609, Aug 2021.

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Last updated: 12/08/2025
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