Worden Laboratory
Structural Biology of Epigenetic Complexes
Approximately 45% of the human genome consists of repetitive DNA sequences derived from endogenous retrotransposons. While formerly derided as “junk” DNA, these ancient mobile DNA elements have played a major role in shaping our genome and continue to pose serious risks to genome integrity and human health. Because of the acute danger of retrotransposon expression, the cell has evolved intricate epigenetic mechanisms to repress retrotransposon expression using both histone and DNA modifications. Our lab leverages cryo-electron microscopy (cryo-EM) to decipher the structural and biochemical mechanisms that regulate the chromatin-modifying complexes that regulate the expression of retrotransposons, which are important for the formation of cancer and are attractive targets for anti-cancer treatments.
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Worden Laboratory
Evan Worden, Ph.D.
Assistant Professor, Department of Structural Biology
Areas of Expertise
Biography
Dr. Evan Worden leverages breakthrough technologies such as cryo-EM to investigate the epigenetic mechanisms underpinning cancer, with a focus on posttranslational histone modifications. He earned his Ph.D. in molecular and cell biology from University of California, Berkeley, under the mentorship of Dr. Andreas Martin. Dr. Worden’s graduate work explored protein degradation by the 26S proteasome and answered long-standing questions about the mechanisms that link ubiquitin removal and protein degradation. From there, he joined the lab of Dr. Cynthia Wolberger at Johns Hopkins University as a postdoctoral fellow. Using cryo-EM and biochemical approaches, he elucidated novel functions of Dot1L and COMPASS, two histone lysine methyltransferases that play key roles in gene transcription. In 2021, Dr. Worden joined Van Andel Institute’s Department of Structural Biology as an assistant professor.
He has earned numerous prestigious awards for his research, including a Damon Runyon Cancer Research Foundation Postdoctoral Fellowship, the Paul Ehrlich Award for Postdoctoral Research from Johns Hopkins, and the Nicholas Cozzarelli Prize for best Ph.D. thesis from University of California, Berkeley. In 2020, he was a finalist for the Damon Runyon Dale Frey Award.
Worden Laboratory
SELECTED PUBLICATIONS
Yan Y, Zhou XE, Thomas SL, Liu M, Lai GQ, Worden EJ, Jones PA, Xu TH. 2025. Mechanisms of DNMT3A-3L-mediated de novo DNA methylation on chromatin. Nat Struct Mol Biol 33:171–183.
*Featured on the cover
Panwar HS, Vos TJ, Xie X, Jang HJ, Lee H, Sheldon RD, Worden EJ, Kothe U. 2025. Interprotomer communication and functional asymmetry in H/ACA snoRNPs. Proc Natl Acad Sci U S A 122(51).
Kariapper L, Marathe IA, Niesman AB, Suino-Powell K, Chook YM, Wysocki VH, Worden EJ. 2025. Setdb1 and Atf7IP form a hetero-trimeric complex that blocks Setdb1 nuclear export. J Biol. Chem. 110171.
Liu Y, Hrit JA, Chomiak AA, Stransky S, Hoffman JR, Tiedemann RL, Wiseman AK, Kariapper LS, Dickson BM, Worden EJ, Fry CJ, Sidoli S, Rothbart SB. 2024. DNA hypomethylation promotes UHRF1-and SUV39H1/H2-dependent crosstalk between H3K18ub and H3K9me3 to reinforce heterochromatin states. Mol Cell.
Rahman S, Hoffmann NA, Worden EJ, Smith ML, Namitz KEW, Knutson BA, Cosgrove MS, Wolberger C. 2022. Multistate structures of the MLL1-WRAD complex bound to H2B-ubiquitinated nucleosome. Proc Natl Acad Sci U S A 119: e2205691119.
Worden EJ, Zhang X, Wolberger C. 2020. Structural basis for COMPASS recognition of an H2B-ubiquitinated nucleosome. eLife 9.
Worden EJ, Wolberger C. 2019. Activation and regulation of H2B-Ubiquitin-dependent histone methyltransferases. Curr Opin Struct Biol 59:98–106.
Worden EJ, Hoffmann NA, Hicks CW, Wolberger C. 2019. Mechanism of cross-talk between H2B ubiquitination and H3 methylation by Dot1L. Cell 176(6):1490–1501.e12.
Worden EJ, Dong KC, Martin A. 2017. An AAA motor-driven mechanical switch in Rpn11 controls deubiquitination at the 26S proteasome. Mol Cell 67(5):799-811.e798.
Dambacher CM*, Worden EJ*, Herzik MA*, Martin A, Lander GC. 2016. Atomic structure of the 26S proteasome lid reveals the mechanism of deubiquitinase inhibition. eLife 5:e13027.
*Co-first authors
Worden EJ, Padovani C, Martin A. 2014. Structure of the Rpn11-Rpn8 dimer reveals mechanisms of substrate deubiquitination during proteasomal degradation. Nat Struct Mol Biol 21:220–227.
Beckwith R, Estrin E, Worden EJ, Martin A. 2013. Reconstitution of the 26S proteasome reveals functional asymmetries in its AAA+ unfoldase. Nat Struct Mol Biol 20(10):1164–1172.
Thoren KL, Worden EJ, Yassif JM, Krantz BA. 2009. Lethal factor unfolding is the most force-dependent step of anthrax toxin translocation. Proc Natl Acad Sci U S A 106(51):21555–21560.
Worden Laboratory
Arkajit De
Ph.D. Student, VAI Graduate School
Research Focus: Engineering a novel biochemical tool to investigate chromatin and epigenetic regulation
Biography
Mentor: Evan Worden, Ph.D.
Research Focus: Engineering a novel biochemical tool to investigate chromatin and epigenetic regulation
Experience: Arkajit is a Ph.D. student in the Worden Laboratory at Van Andel Institute in the Department of Structural Biology. His research focuses on developing a novel in vitro biochemical tool to study chromatin and epigenetic regulation mediated by chromatin-modifying complexes. By integrating cryo-electron microscopy with biochemical assays, he aims to uncover fundamental mechanisms of chromatin regulation and gene transcription relevant to cancer. Before joining the Graduate School, he earned a Bachelor of Technology in biotechnology from Adamas University, Kolkata, India, where he was an undergraduate student researcher in Dr. Kuntal Pal’s lab. His work focused on computer-aided drug design and chemoinformatics, particularly in the screening of small-molecule inhibitors targeting GPCRs and viral proteins from SARS-CoV-2, Nipah virus and Marburg virus, using molecular docking, dynamics and virtual screening approaches.
Undergraduate Institution: Adamas University
Hometown: Chandannagar, West Bengal, India
Publications
De A, Subramanian S, Nayak P, Pal K. 2025. In silico drug repurposing of potential antiviral inhibitors targeting methyltransferase (2′ O MTase) domain of Marburg virus. In Silico Pharmacol 13:70.
Debroy B, De A, Bhattacharya S, Pal K. 2023. In silico screening of herbal phytochemicals to develop a Rasayana for immunity against Nipah virus. J Ayurveda Integr Med 14(6):100825.
De A, Bhattacharya S, Debroy B, Basak A, Nayak P, Pal K. 2023. Exploring the pharmacological aspects of natural phytochemicals against SARS CoV 2 Nsp14 through an in silico approach. In Silico Pharmacol 11:12.
Barman N, De A, Paul J, Haldar S, Bhattacharya A, Pal K. 2022. Strategy to configure multi epitope recombinant immunogens with weightage on proinflammatory response using SARS CoV 2 spike glycoprotein (S protein) and RNA dependent RNA polymerase (RdRp) as model targets. J Pure Appl Microbiol 16(1):281–295.
Nancy Duchaine
Senior Administrative Assistant I, Department of Structural Biology
Biography
Anjali Malik, Ph.D.
Research Scientist, Department of Structural Biology
Shantinique Miller
Ph.D. Student, VAI Graduate School
Thesis: Determining how intracellular bacteria pathogens interact with the human genome
Biography
Undergraduate university: Central State University
Thesis: Determining how intracellular bacteria pathogens interact with the human genome
Mentor: Evan Worden, Ph.D.
Experience:
- Chemistry in art conservation
- Extraction and analysis of bioactive extracts
- Computational physics
- Antimicrobial and cytotoxic properties of corn silk extracts
- Equipment including gas chromatography, mass spectrometry, UV vis spectrometer, hydrodistillation, solvent extractor, hydroponic system, microbial cell culturing
Hometown: The Bahamas
Hobbies: Go-karts, binge watching Law & Order and cooking.
Quoc Phong Nguyen, Ph.D.
Postdoctoral Fellow, Worden Laboratory
Hemendra Panwar, Ph.D.
Postdoctoral Fellow, Worden Laboratory
Biography
Dr. Xiaoyan Xie earned her B.S. in biological science from Anhui Normal University and her Ph.D. in biochemistry and molecular biology from the Institute of Biophysics, Chinese Academy of Sciences. Her graduate studies focused on structural and functional study of histone chaperones as well as histone variants. In 2019, she joined the laboratory of Dr. Peter Jones at Van Andel Institute as a postdoctoral fellow and was promoted to research scientist in 2025.