Assistant Professor of Chemistry
Nucleic acids are decorated with diverse types of chemical modifications that play essential regulatory functions in biology. Chemical modifications can change electrostatics, hydrophobicity, steric hindrance and hydrogen bonding propensity of the modified moieties (i.e. nucleobase and sugar-phosphodiester backbone), altering nucleic acids structure, stability and interactions with adjacent molecules. Dysregulations of the chemical modification landscapes and their effector proteins have been found closely relevant in abnormal cellular functions, development disorders and diseases. The Zhou research group focuses on developing and applying new technologies to visualize spatial and temporal distributions of chemical modifications in the mammalian transcriptome at base-resolution. We are interested in studying molecular mechanisms of how chemical modifications and their regulatory network control gene expression. We also develop tools to modulate transcript-specific RNA modification level in order to revert dysregulated epitranscriptome in diseases. We approach these interdisciplinary projects using directed evolution, protein engineering, RNA and enzyme biochemistry, mass spectrometry, next-generation sequencing, bioinformatics and structural biology. Collectively, our research program aims to achieve in-depth understanding of regulatory mechanisms of epitranscriptome that can lead to discoveries of novel drug targets, and to diversify the tool box of gene therapy.
Chicago Fellows Fellowship 2017
Zhou, H.; Rauch, S.; Dai, Q.; Cui, X.; Zhang, Z.; Nachtergaele, S.; Sepich, C.; He, C.; Dickinson, B.C. (2019) Evolution of A Reverse Transcriptase to Map N1-Methyladenosine in Human mRNA. Nature Methods., 16, 1281-1288.
Zhou, H.; Sathyamoorthy, B.; Stelling, A.; Xu, Y.; Xue, Y.; Pigli, Y. Z.; Case, D.; Rice, P. A.; Al-Hashimi, H. M. (2019) Resolving crystallographic ambiguity in Watson-Crick versus Hoogsteen base-pairing in a DNA-protein complex using NMR and site-specifically 13C/15N labeled DNA. Biochemistry, 58, 1963-1974.
Zhou, H.; Kimsey, I. J.; Nikolova, E. N.; Sathyamoorthy, B.; Grazioli, G.; McSally, J.; Bai, T.; Wunderlich, C. H.; Kreutz, C.; Andricioaei, I.; Al-Hashimi, H. M. (2016) m1A and m1G disrupt A-RNA structure through the intrinsic instability of Hoogsteen base pairs. Nat. Struct. Mol. Biol., 23, 803-810.
Zhou, H.; Hintze B.J.; Kimsey, I. J.; Sathyamoorthy, B.; Yang S.; Richardson, J.S.; Al-Hashimi, H. M. (2015) New insights into Hoogsteen base pairs in DNA duplexes from a structure-based survey. Nucleic Acids Res., 43, 3420-3433.