Brittany Morgan

Brittany Morgan

Molecular Recognition of Dynamic & Disordered Proteins for Cancer Drug Discovery

Biography

2022
John V. O'Connor Assistant Professor in Cancer Drug Discovery, University of Notre Dame
2018-present
Michigan May-Walt Life Sciences Postdoctoral Fellow, University of Michigan
2018
Ph.D. in Chemistry, Duke University
2012
B.S. in Biochemistry, Western Kentucky University

Selected Awards

2022-2027
Burroughs Wellcome Fund Career Award at the Scientific Interface
2021
Outreach Excellence Award, Life Sciences Institute, University of Michigan
2020-2022
Ruth L. Kirschstein National Research Service Award Postdoctoral Fellowship
2018
Dean's Award for Excellence in Mentoring, Duke University
2017-2018
Katherine Goodman Stern Fellowship
2015
Burroughs Wellcome Fellowship for Organic Chemistry
2012
Western Kentucky University Scholar of the Ogden College of Science & Engineering

Research Interests

The classic paradigm that only folded protein structure leads to function has been rewritten to recognize the significant role dynamic and/or disordered regions play in biology. These structures are central to protein ensembles and allosteric networks, signaling hubs and cellular machines, and the formation and dissolution of biomolecular condensates. Dynamic and disordered proteins have also been implicated as drivers of numerous diseases and thus are promising therapeutic targets. These structures, however, are largely considered unligandable and consequently undruggable.

The Morgan lab uses covalent small molecules to capture dynamic and/or disordered protein structures and study their molecular recognition. Through our approach, we answer many broad and fundamental questions: Can dynamic and/or disordered regions be targeted specifically and selectively with small molecules? What are the molecular interactions that form between the ligand and protein? How does the ligand alter the structure and conformational landscape of the protein? Does small molecule binding to these regions alter protein activity?

To answer these questions, our lab uses RNA-binding proteins (RBPs) as a model system. RBPs are enriched with dynamic and disordered regions, are genetically mutated in over 200 diseases, and have largely eluded selective small molecule targeting. Our initial focus is on i) developing covalent ligand discovery strategies tailored to dynamic loops and intrinsically disordered regions; and ii) applying our approach to target RBPs that are essential for cancer proliferation and metastasis. The selective targeting of RBPs will provide critical tools to explore RBP structure, function, and therapeutic potential. It will also expand the types of structures that can be targeted with small molecules, significantly increasing our ligandable proteome.

Research in the Morgan lab is highly interdisciplinary. We utilize computational methods to design covalent libraries, medicinal chemistry to optimize ligands into preclinical drug candidates, and biochemical, structural, biophysical, and cell culture techniques to characterize the effects of ligands on RBP structure and function.

The Morgan lab will open in July 2022. Interested postdocs, graduate students, post-baccalaureates, and undergraduates are encouraged to inquire about open positions.

Recent Publications

  • Henley, M. J., Linhares, B. M., Morgan, B. S., Cierpicki, T., Fierke, C. A., Mapp, A. K. "Unexpected Specificity within Dynamic Transcriptional Protein-Protein Complexes" 2020 Proceedings of the National Academy of Sciences of the United States of America, 117 (44), pp. 27346-27353. DOI:10.1073/pnas.2013244117.
  • Morgan, B. S., Sanaba, B. G., Donlic, A., Karloff, D. B., Forte, J. E., Zhang, Y. Q., Hargrove, A. E. "R-BIND: An Interactive Database for Exploring and Developing RNA Targeted Chemical Probes" 2019 ACS Chemical Biology, 14 (12), pp. 2691-2700. DOI:10.1021/acschembio.9b00631.
  • Donlic, A., Morgan, B. S., Xu, J. L., Liu, A. Q., Roble, C., Hargrove, A. E. "Discovery of Small Molecule Ligands for MALAT1 by Tuning an RNA-Binding Scaffold" 2018 Angewandte Chemie-International Edition, 57 (40), pp. 13242-13247. DOI:10.1002/anie.201808823.
  • Morgan, B. S., Forte, J. E., Hargrove, A. E. "Insights into the development of chemical probes for RNA" 2018 Nucleic Acids Research, 46 (16), pp. 8025-8037. DOI:10.1093/nar/gky718.
  • Morgan, B. S., Forte, J. E., Culver, R. N., Zhang, Y. Q., Hargrove, A. E. "Discovery of Key Physicochemical, Structural, and Spatial Properties of RNA-Targeted Bioactive Ligands" 2017 Angewandte Chemie-International Edition, 56 (43), pp. 13498-13502. DOI:10.1002/anie.201707641.
  • Burg, J. M., Link, J. E., Morgan, B. S., Heller, F. J., Hargrove, A. E., McCafferty, D. G. "KDM1 Class Flavin-Dependent Protein Lysine Demethylases" 2015 Biopolymers, 104 (4), pp. 213-246. DOI:10.1002/bip.22643.

Contact Information

  • John V. O'Connor Assistant Professor in Cancer Drug Discovery
  • Send an email

Primary Research Areas

Research Specialties