Katherine Albanese

Education

BS in Chemistry, 2016 Wake Forest University

PhD in Chemistry, 2021 UNC Chapel Hill

Postdoctoral Researcher, 2021-2024, University of Bristol, UK

Research Description

Histone posttranslational modifications (PTMs) are crucial regulatory components for many cellular processes. The readout of histone PTMs is dependent both on the chemical modification as well as the specific site on the histone protein. The array of histone PTMs on chromatin is highly dynamic and relies on many protein interactions throughout the eukaryotic life cycle. In the Albanese Lab, our combined protein design-chemical biology-cell biology approach is geared toward enhancing fundamental understanding of epigenetic pathways in both healthy and diseased cells, and for developing novel insights into the most tractable therapeutic targets.

De novo protein design: We apply a rationally seeded computational protein design approach to engineering and designing new proteins for studying histone epigenetics. Our pipelines are guided by first principles—specifically, our understanding of molecular recognition of histone PTMS—and use continuously evolving protein design and modelling tools. 

gene regulation: At its core, the Albanese Lab aims to address a classical biochemistry question: how does a single mutation in protein sequence affect a biological pathway? In the context of the nucleosome, our goal is address this question in three main areas (1) new and putative histone PTMs, (2) aberrant and oncogenic histone mutations and (3) the combinatorial histone code.

chemical and synthetic biology: Synthetic cells provide a more complex environment than a test tube while being more controllable than cells. Our goal is to add synthetic cells to the epigenetic research toolbox for testing hypotheses and characterizing new or putative mechanisms of posttranslational regulation.

Publications

Albanese, K. I.*, Petrenas, R.*, Pirro, F., Naudin, E. A., Borucu, U., Dawson, W. M., Scott, D. A., Leggett, G. J., Weiner, O. D., Woolfson, D. N., Rationally seeded computational protein design of ⍺-helical barrels. Nat. Chem. Biol., 2024 (featured on the cover for this issue)

Travis, C. R., Kean, K. M., Albanese, K. I., Henriksen, H. C., Treacy, J. W., Chao, E. Y., Houk, K. N., Waters, M.  L., Trimethyllysine reader proteins exhibit widespread charge-agnostic binding via different mechanisms to cationic and neutral ligands. J. Am. Chem. Soc. 2024, 146, 5, 3086–3093

Naudin, E. A., Albanese, K. I., Smith, A. J., Mylemans, B., Baker, E. G., Weiner, O. D., Andrews, D. M., Tigue, N., Savery, N. J., Woolfson, D. N., From peptides to proteins: 1. coiled-coil tetramers to single-chain 4-helix bundles. Chem. Sci. 2022, 13, 11330-11340

Albanese, K. I., Leaver-Fay, A., Treacy, J. W., Park, R., Houk, K. N., Kuhlman, B., & Waters, M. L., Comparative Analysis of Sulfonium−π, Ammonium−π, and Sulfur−π Interactions and Relevance to SAM-Dependent Methyltransferases. J. Am. Chem. Soc, 2022, 144(6), 2535-2545

Albanese, K. I.; Waters, M. L., Contributions of methionine to recognition of trimethyllysine in aromatic cage of PHD domains: implications of polarizability, hydrophobicity, and charge on binding. Chem. Sci. 2021, 12, 8900-8908.

Krone, M. W.*; Albanese, K. I.*; Leighton, G. O.; He, C. Q.; Lee, G. Y.; Garcia-Borras, M.; Guseman, A. J.; Williams, Jr., D. C.; Houk, K. N.; Brustad, E. M.; Waters, M. L., Thermodynamic Consequences of Tyrosine to Tryptophan Mutations in the Cation-π-Mediated Binding of Trimethyllysine by the HP1 Chromodomain. Chem. Sci. 2020, 11, 3495-3500.

Albanese, K. I.*; Krone, M. W.*; Petell, C. J.*; Parker, M. M.; Strahl, B. D.; Brustad, E. M.; Waters, M. L. Engineered Reader Proteins for Detection of Methylated Lysine on Histones. ACS Chem. Biol. 2020, 15, 103-111. (featured on the cover for this issue)

Baril, S. A., Koenig, A. L., Krone, M. W., Albanese, K. I., He, C. Q.; Lee, G. Y., Houk, K. N., Waters, M. L., Brustad, E. M., Investigation of Trimethyllysine Binding by the HP1 Chromodomain via Unnatural Amino Acid Mutagenesis. J. Am. Chem. Soc. 2017, 139, 17253-17256.