The Hall lab’s major research focuses on the in silico development of novel anti-stringent responses (bacterial virulence factors and toxins), and biofilm agents for the treatment of persistent infections. Dr. Hall’s work bridges the gap between in silico modeling and in vitro studies of bacterial therapeutic agents.

Current lab members:

• Michiko Thwe (PhD, Biomedical Engineering – co-advisor with Dr. Ehrlich)
• Karan Bamb (MS, Molecular and Cell Biology and Genetics – co-advisor Dr. Mell)
• Felicity Tso (MS, Microbiology & Immunology)
• Carl Quilbilan-Cruz (Undergraduate, CoAS Biology)

Research Interests: Computational drug design, structural bioinformatics, preclinical drug development, bacterial multi-drug tolerance, bacterial stringent response, bacterial persister cells, molecular diagnostics, and development and testing of novel antimicrobial materials

Multiprong Approach to Chronic Infections

Development of drug molecules for the treatment of chronic infections. Because of the significant role that biofilms play in clinical infections, it is imperative to find a way to inhibit biofilm formation and induce biofilm degradation; this would subsequently re-potentiate antibiotics. My lab focuses on the design and testing of small molecule inhibitors for the enzymes RelA and more generally RSH (RelA/SpoT homologs). These alarmones induce a major change in cellular metabolism whereby the bacteria are converted into persister cells, inducing toxin and virulence factor production pathways.

Persister cells have upregulated genes (such as chaperones, toxin/antitoxin systems, and oxidative stress protection) and downregulated genes involved in cell wall synthesis, translation, and DNA replication. All these factors make them up to one thousand times more resistant to antibiotics than their planktonic counterparts.

Using computational models, organic synthesis, and in vivo and in vitro assays; our team aims to produce novel therapeutic compounds and evaluate their ability to interrupt the stringent response as well as re-potentiate antibiotics for the treatment of infectious bacteria biofilms.

Novel Antimicrobial Materials

My lab is interested in the development of antimicrobial materials. Our latest work involves surfactant-impregnated metal organic framework coated fabrics. This is the first reported antimicrobial MOF that uses a cationic surfactant (benzalkonium chlorides) as the active agent. The MOF is a non-toxic material consisting of a γ-cyclodextrin molecule with a potassium ion linker. This design allowed epitaxial growth on polypropylene fabric (commonly used in face masks). Our team was able to demonstrate that the surfactant impregnated MOFs were then effective at killing a myriad of microbes including beta coronaviruses.

Simulation of γ-CD-MOF-1 impregnated with benzalkonium chloride molecule bound into the pore structure.

Patents

Ji H-F, Ehrlich GD, Hall Jr DC, Krol JE, Cahill JP. RelA Inhibitors for Biofilm Disruption. US Patent App. 16/610,376; 2020

Please see a full list of publications on my Google Scholar page.

Selected Publications

“Surfactant-Impregnated MOF-Coated Fabric for Antimicrobial Applications”
Schwenk, G. R.; Glass, A. M.; Ji, H.-F.; Ehrlich, G. D.; Navas-Martin, S.; Król, J. E.; Hall, D. C., Jr.
ACS Applied Bio Materials. 2023 January; 6 (1), 238

“Bacterial Biofilm Growth on 3D-Printed Materials”
Hall Jr. D. C., Palmer P., Ji H., Ehrlich G, Król J
Frontiers in Microbiology. May 2021 12:646303

“The Development of a Pipeline for the Identification and Validation of Small-Molecule RelA Inhibitors for Use as Anti-Biofilm Drugs”
Hall Jr. D. C., Król J, Cahill J, Ji H, Ehrlich G
Microorganisms. 2020 August 28; 8(9):1310

“A search for medications to treat COVID-19 via in silico molecular docking models of the SARS-CoV-2 spike glycoprotein and 3CL protease”
Hall Jr. D. C., Ji H
Travel Medicine and Infectious Disease. 2020 May; 35:101646

“Fibrous Phosphorus Quantum Dots for Cell Imaging”
Hall Jr. D. C., Amaral P, Pai R, Król J, Kalra V, Ehrlich G, Ji H
ACS Applied Nano Materials. 2020 January 07; 3(1):752

“Genome rearrangements induce biofilm formation in Escherichia coli C – an old model organism with a new application in biofilm research”
Król J, Hall Jr. D. C., Balashov S, Pastor S, Sibert J, McCaffrey J, Lang S, Ehrlich R, Earl J, Mell J, Xiao M, Ehrlich G
BMC Genomics. 2019 October 22; 20(1):767