Leifu Chang
Research Areas
Research
The Chang laboratory investigates the molecular basis of genome function and its regulation. We study how programmable RNA-guided systems couple sequence-specific recognition to distinct biological activities, including DNA cleavage, integration, and transcription. We combine single-particle cryo-electron microscopy with biochemical reconstitution and functional analysis to understand how these molecular machines assemble and act on their targets.
DNA transposition
CRISPR-associated transposons (CASTs) couple programmable DNA recognition to the machinery of DNA transposition. Our work on type I-B CRISPR-associated transposons and the related TnsD-guided targeting pathway examines how different recognition mechanisms direct transpososome assembly and DNA integration.
Transcription and gene regulation
We investigate how RNA-guided systems control gene expression. We established the structural basis of natural RNA-guided transcriptional activation by a dCas12f–σE–RNA polymerase complex. This work addresses how an RNA-guided effector recruits the bacterial transcription machinery.
CRISPR-Cas systems and bacterial defense
We investigate how CRISPR-Cas activity is regulated in bacterial defense, including how anti-CRISPR proteins inhibit target recognition or catalytic activation. These studies reveal the molecular interactions and conformational changes that control CRISPR-Cas function and may inform the rational design of improved genome editing tools.
Selected publications
Structural basis of RNA-guided transcription by a dCas12f-σE-RNAP complex.
Xiao, R., Hoffmann, F. T., Xie, D., Wiegand, T., Palmieri, A. I., Sternberg, S. H., and Chang, L.
Nature 653, 288-296 (2026).
Exapted CRISPR-Cas12f homologues drive RNA-guided transcription.
Hoffmann, F. T., Wiegand, T., Palmieri, A. I., Glass-Klaiber, J., Xiao, R., Tang, S., Le, H. C., Meers, C., Lampe, G. D., Chang, L., and Sternberg, S. H.
Nature 653, 277-287 (2026).
Structure of TnsABCD transpososome reveals mechanisms of targeted DNA transposition.
Wang, S., Siddique, R., Hall, M. C., Rice, P. A., and Chang, L.
Cell 187, 6865-6881.e16 (2024).
Molecular mechanism for Tn7-like transposon recruitment by a type I-B CRISPR effector.
Wang, S., Gabel, C., Siddique, R., Klose, T., and Chang, L.
Cell 186, 4204-4215.e19 (2023).
Structural basis of AcrIF24 as an anti-CRISPR protein and transcriptional suppressor.
Mukherjee, I. A., Gabel, C., Noinaj, N., Bondy-Denomy, J., and Chang, L.
Nature Chemical Biology 18, 1417-1424 (2022).
Structural basis of target DNA recognition by CRISPR-Cas12k for RNA-guided DNA transposition.
Xiao, R., Wang, S., Han, R., Li, Z., Gabel, C., Mukherjee, I. A., and Chang, L.
Molecular Cell 81, 4457-4466.e5 (2021).
Full publication list on Google Scholar
Academic appointments
2026–present | Professor, Purdue University
2023–2026 | Associate Professor, Purdue University
2018–2023 | Assistant Professor, Purdue University
2013–2017 | Investigator Scientist, MRC Laboratory of Molecular Biology, Cambridge, UK
2012–2013 | Postdoctoral Researcher, The Institute of Cancer Research, London, UK
Education
2012 | Ph.D. in Biophysics, Tsinghua University, Beijing, China
Selected honors
2026 | College of Science Research Award, Purdue University
2024 | NSF CAREER Award, National Science Foundation
2024 | University Faculty Scholar/Showalter Faculty Scholar, Purdue University