Matthew Lawrenz Lab

About

In the Matthew Lawrenz lab, part of the UofL School of Medicine, researchers are working to understand:

Evasion of Innate Immunity During Plague: To kill invading bacteria, innate immune cells deploy potent antimicrobial mechanisms such as the production of inflammatory lipids. Yersinia pestis, which causes the plague, can inhibit these mechanisms by injecting proteins into macrophages and neutrophils through an apparatus called a Type 3 Secretion System. We are interested in understanding how Y. pestis evades innate immunity by inhibiting the production of inflammatory lipids and altering the packaging of extracellular vesicles.

Metal Acquisition by Bacteria During Infection: Bacteria require metals for growth. As such, our bodies restrict access to metals through mechanisms referred to as nutritional immunity. Bacterial pathogens can overcome nutritional immunity by secreting small molecules called metallophores that steal metals from their hosts. We are defining the role of metallophores in microbial virulence and working to develop therapeutics that target metal acquisition systems.

New Drugs to Combat Antimicrobial-Resistant Infections: We have developed validated preclinical models to test novel antibiotics against multidrug-resistant Pseudomonas aeruginosa. These models are key to identifying promising new antimicrobial drugs and providing proof-of-concept data that can be used to justify in-human clinical trials and support subsequent FDA approval. We maintain support for these preclinical models for researchers interested in antimicrobial development.

Key Research Areas

Bacterial pathogenesis and immune evasion
Bacterial genetics
Innate immune responses to bacterial infection
Animal models to study infection and develop novel vaccines and therapeutics

Team

Matthew B. Lawrenz, PhD, Principal Investigator
Mahendar Kadari, PhD, Postdoctoral Research Associate
Katelyn Whitefoot-Keliin, PhD, Postdoctoral Research Associate
Taylor Garrison, MS, M&I PhD Candidate, 2020
Katelyn Sheneman, MS, M&I PhD Candidate, 2020
Subarna Roy, MS, M&I PhD Student, 2022
Ben Hammond, MS, Research Technician
Leo Mora Martinez, Research Technician
Briana Harness, UofL BIOMED PREP Scholar
Eman Hamada, High School Intern

Recent Publications

View full publication profile here.

Brady, A., L. Mora-Martinez, B. Hammond, B. Haribabu, S.M. Uriarte, and M.B. Lawrenz. 2024. Recognition of the T3SS by distinct mechanisms governs LTB4 synthesis in macrophages and neutrophils. bioRxiv 2024.07.01.601466; https://doi.org/10.1101/2024.07.01.601466.
Brady, A., M. Tomaszewski, and M.B. Lawrenz. 2024. Approaches for the Inactivation of Yersinia pestis. Applied Biosafety. https://doi.org/10.1089/apb.2023.0022.
Brady, A., K.R.,Sheneman, A.R. Pulsifer, S.L. Price, Garrison, T.M., Maddipati, K.R., Bodduluri, S.R., Pan, J., Boyd, N.L., Zheng, J.J., Rai, S.N., Hellmann, J., B. Haribabu, S.M. Uriarte, and M.B. Lawrenz. 2024. Type 3 secretion system induced leukotriene B4 synthesis by leukocytes is actively inhibited by Yersinia pestis to evade early immune recognition. PLoS Pathogens, 20(1), e1011280. doi.org/10.1371/journal.ppat.1011280. PMID: 38271464.
Price, S.L., R.S. Oakes, R. Gonzalez, J.K. DeMarco, A. Brady, C.M. Jewell, and M.B. Lawrenz. 2023. Microneedle array delivery of Yersinia pestis recapitulates bubonic plague. iScience. 2023 Nov 30;27(1):108600. doi: 10.1016/j.isci.2023.108600. PMID: 38179062.
Price, S.L., D. Thibault, T.M. Garrison, A. Brady, H Guo, T.E. Kehl-Fie, S. Garneau-Tsodikova, R.D. Perry, T. van Opijnen, and M.B. Lawrenz. 2023. Droplet Tn-Seq identifies the primary secretion mechanism for yersiniabactin in Yersinia pestis. EMBO Rep. 2023 Jul 28:e57369. doi: 10.15252/embr.202357369. PMID: 37501563.
Warawa, J.M., X. Duan, C.D. Anderson, J.B. Sotsky, D.E. Cramer, T.L. Pfeffer, H. Guo, S. Adcock, S.A. Slone, A.J. Stromberg, A.J. Lepak, D.R. Andes, J.D. Gabbard, W.E. Severson, and M.B. Lawrenz. 2022. Validated preclinical murine model for therapeutic testing against multidrug resistant Pseudomonas aeruginosa. Microbiol Spectr. 2022 Oct 26;10(5):e0269322. doi: 10.1128/spectrum.02693-22. Epub 2022 Sep 12. PMID: 36094219.
Behnsen J., Zhi H., A. Aron, V. Subramanian, W. Santus, M.H. Lee, R.R. Gerner, D. Petras, J.Z. Liu, K.D. Green, S.L. Price, J. Camacho, H. Hillman, J. Tjokrosurjo, N.P. Montaldo, E. Hoover, S. Treacy-Abarca, B.A. Gilston, E.P. Skaar, W.J. Chazin, S. Garneau-Tsodikova, M.B. Lawrenz, R.D. Perry, S. Nuccio, P.C. Dorrestein, and M. Raffatellu. 2021. Siderophore-mediated zinc acquisition enhances enterobacterial colonization of the inflamed gut. Nat Commun. 2021 Dec 1;12(1):7016. doi: 10.1038/s41467-021-27297-2.PMID: 34853318
Price, S.L., V. Vadyvaloo, J.K. DeMarco, A. Brady, P.A. Gray, T.E. Kehl-Fie, S. Garneau-Tsodikova, R.D. Perry, and M.B. Lawrenz. 2021. Yersiniabactin contributes to overcoming zinc restriction during Yersinia pestis infection of mammalian and insect hosts. Proc Natl Acad Sci U S A. 2021 Nov 2;118(44):e2104073118. doi: 10.1073/pnas.2104073118. PMID: 34716262.
DiNubile M.J., S.L. Levinson, T.P. Stossel, M.B. Lawrenz, and J.M. Warawa. 2020. Recombinant human plasma gelsolin (RHU-PGSN) improves survival and attenuates lung injury in a murine model of virulent Pseudomonas aeruginosa pneumonia. Open Forum Infectious Diseases, doi.org/10.1093/ofid/ofaa236. PMID: 32766380.

Lawrenz Lab Alumni

Amanda Brady, PhD - Postdoctoral Associate, University of Colorado (Doran Lab)
Sarah Price, PhD - Postdoctoral Associate, Vanderbilt (Skaar Lab)
Amanda Pulsifer, PhD - Senior Scientific Support, STEMCELL Technologies
Shane Reeves, MD/MPH - Resident Physician, Wayne State University
Stephanie Lunn, MPH, MS - Bioinformatician, Washington State Department of Health
Tiva VanCleave, PhD - High Cost Drug Analyst, Rawlings Group
Yanwen Sun, MS - Medical Laboratory Scientist, University of Iowa
Michael Connor, PhD - Pasteur Foundation Fellow/Postdoctoral Scholar, Institut Pasteur (Hamon Lab)