Robert K. Ernst, PhD

The focus of my laboratory is to understand the molecular basis by which bacteria (Gram-negative and positive) modify the lipid component of their membrane and how these alterations affect or circumvent normal host innate immune system responses. These modifications can promote resistance to host innate immune killing mechanisms by antimicrobial compounds and alter recognition by TLR4. To the end, I have extensive experience in the discovery and analysis of various structural modification of lipopolysaccharide (LPS), the major component of the Gram-negative bacterial envelope and lipoteichoic acid (LTA), the major component of the Gram-positive bacterial. In addition, we have been using a variety of infection routes (aerosol, subcutaneous, IP) to determine the role of the host innate and adaptive immune systems in the control of mutant strains with defects in enzymes required for lipid biosynthesis. We are utilizing mass spectrometry, gas chromatography, and bioinformatics to identify genes required for lipid biosynthesis and their interactions with the host innate immune system, specifically components of the TLR4 complex. 

Additionally, I serve as the Co-Director of the recently established Spatial Systems Biology Laboratory (SSBL), a spatial ‘omics imaging biocontainment suite for workflows developed specifically for a variety of BSL-2, BSL-3, and select agent BSL-3 pathogen models at the University of Maryland School of Dentistry. We are currently developing a novel lipidomic approach for rapidly identifying bacterial and fungal organisms directly from urine, blood, BAL fluid without the need for culture and an associated machine learning/AI software package that can be used to automatically identify organisms directly from mass spectrum. We have also commenced a large-scale surveillance project to identify microorganisms from the Chesapeake Bay that grow at reduced temperatures using lipidomics, where these results will be combined with sequence metagenomics of bulk water samples and 16S sequencing of individual organisms with researchers at the US Naval Academy. Finally, through the characterization of lipid A biosynthetic enzymes, we have developed unique TR4 agonists that are currently being developed as vaccine adjuvants. 

Contract, NIH/NIAID (PI): Adjuvant development of the TLR4 ligand BECC470s (2023-2028) Develop the adjuvant potential of BECC470s through IND-enabling studies.

R21, NIH/NIAID (MPI): Microbial adaptation of Pseudomonas lipid A structure in CF airway disease progress (2023-2025) Use spatial metabolomics and lipid A mapping to correlate the relationship between Pa lipid A and the host lung response.

 R43, NIH/NIAID (subcontract): Rapid Microbial ID Direct from Specimen (2023-2024) Develop a prototype clinical assay to evaluate clinical specimens for identification of pathogens using MS without ex vivo growth.

 R01, NIH/NIAID (Co-I): Structural determinants of activity and mechanism of cationic peptide antibiotic activity against colistin-resistant bacteria (2023-2028) Determine how resistance patterns of levels of colistin resistance correlate with the quantities of amino-containing moieties in lipid A.

Cystic Fibrosis Foundation (PI): Characterization of airway responses to adaptive P. aeruginosa lipid A structural variants in CF (2023-2025) Determine the prevalence of specific lipid A biosynthetic enzyme alterations in a diverse cohort of clinical Pa isolates and evaluate the host response.

R01, NIH/NIAID (Co-I): A prophylactic vaccine to prevent colonization by Pseudomonas aeruginosa (2022-2027) Develop a prophylactic vaccine using the BECC adjuvant system to prevent initial colonization by P. aeruginosa.

R01, NIH/NIAID (Co-I): Repurposing Gram-Positive Antibiotics for Gram-negative Bacteria using Antibiotic Adjuvants (2022-2027) Elucidate specific changes in the structure of lipid A A. baumannii to determine the effect of the novel compounds to specifically downregulate LPS alterations.

DOD, (Co-I): Pain and the Immune System: A Novel Therapeutic Approach (2021-2025) Examine altering the host innate immune response in treating chronic pain.

R21, NIH/NIA (Co-I): Preventing Alzheimer's Disease with Designer Lipids (2021-2023) Determine the compatibility of a probiotic strain with long-term gut colonization in a mouse model of Alzheimer’s disease.

R01, NIH/NIDCR (Co-I): Novel Target Identification for Treatment of Chronic Overlapping Pain Using Multimodal Brain Imaging (2020-2024) Determine novel biomarkers and therapeutic targets for chronic overlapping pain conditions.

R01, NIH/NIAID (MPI): Colistin resistance in extensively drug-resistant Gram-negative pathogens (2020-2025) Develop quantitative test for colistin resistance that is clinically applicable and elucidate remodeling of lipid A.

R01, NIH/NIAID (MPI): MS diagnostic bacterial identification library (2020-2025) Establish a rapid, small scale extraction procedure for lipids isolated from bacterial and fungal pathogens.          

DOD, (PI): Novel Live Vaccines with Modified Lipid A for the Prevention of Shigella Diarrheal Disease (2019-2023 NCE) Engineer and evaluate live attenuated Shigella subspecies vaccines with alterations in lipid A molecule for use as a live oral vaccine.

Contract, NIH/NIAID (PI): Adjuvant development of the TLR4 ligand, BECC438 (2018-2023 NCE) Develop the adjuvant potential of BECC438 through IND-enabling studies.

R01, NIH/NIAID (Co-I): Development of Antibiotic Adjuvants for Gram-Negative Bacteria (2018-2023 NCE) Elucidate changes in the structure of lipid A to novel small molecule antimicrobial.