Roberto N. De Guzman

Professor
PhD, UMBC 1998
Post Doc, Scripps Research Institute, CA
Primary office:
(785) 864-4923
ISB 3116


Summary

Structures and molecular interactions of virulence proteins

Our research is aimed at understanding the structures and molecular interactions of virulence proteins that are required by pathogens to cause infectious diseases in humans.  The relevance of our research in public health is in the area of antibiotic resistance.  In particular, we study nanoinjectors of the bacterial type III secretion system.  These are nanoscale syringes assembled by pathogens from many proteins, and used to inject virulence proteins directly into human cells to cause infectious diseases.   We seek to understand how nanoinjectors are assembled and how small molecules can disrupt this assembly.

Nanoinjectors are absolutely essential in the pathogenesis of many bacteria.  For example, annually, Shigella is estimated to cause up to 1.1 million deaths worldwide, including 350,000 deaths in young children.  There are recurring Salmonella outbreaks in our food supply.  There are still sporadic outbreaks of Yersinia pestis, which caused the Black Death in Europe during medieval times that altered the trajectory of human history.  Among cystic fibrosis patients, secondary lung infection by Pseudomonas aeruginosa is the major cause of death. All pathogens that require nanoinjectors for infectivity have developed resistance to current antibiotics.

There is therefore a need to develop new antibiotics against these pathogens.  Bacterial nanoinjectors are exposed on the bacterial surface and are present only among pathogens, thus, disrupting their assembly is an attractive approach for developing novel anti-infectives.  This approach requires a detailed understanding of the structures and molecular interactions involved in the assembly of nanoinjectors.  We use NMR and biophysical methods to determine the structures, protein-protein interactions, and small molecule-protein interactions of nanoinjectors.

Representative Publications

1. Kato J, Dey S, Soto JE, Butan C, Wilkinson MC, De Guzman RN, Galan JE.   A protein secreted by the Salmonella type III secretion system controls needle filament assembly. eLife, In press, 2018.

 

2. Dey S, Anbanandam A, Mumford BE, De Guzman RN.   Characterization of Small Molecule Scaffolds that Bind to the Shigella Type III Secretion System Protein IpaD. ChemMedChem, 12, 1534-1541, 2017.

 

3. Kaur K, Park H, Pandey N, Azuma Y, De Guzman RN.   Identification of a New SUMO-Interacting Motif in PIASy. J. Biol. Chem, 292, 10230-10238, 2017.

 

4. Kaur K, Wu X, Fields JK, Johnson DK, Lan L, Pratt M, Somoza AD, Wang CCC, Karanicolas J, Oakley BR, Xu L, De Guzman RN.   The Fungal Natural Product Azaphilone-9 Binds to HuR and Inhibits HuR-RNA Interaction in Vitro. PLoS One, 12, e0175471, 2017.

Full list of publications.

Search PubMed publications of Roberto N. De Guzman.


Home to 50+ departments, centers, and programs, the School of the Arts, and the School of Public Affairs and Administration
KU offers courses in 40 languages
No. 1 ranking in city management and urban policy —U.S. News and World Report
One of 34 U.S. public institutions in the prestigious Association of American Universities
44 nationally ranked graduate programs.
—U.S. News & World Report
Top 50 nationwide for size of library collection.
—ALA
23rd nationwide for service to veterans —"Best for Vets," Military Times
KU Today