Advancing Mentorship at the Johns Hopkins Integrated Center for Combating Antimicrobial Resistant Bacteria

Project Summary I am passionate about identifying novel approaches to treating antimicrobial resistant (AMR) infections in children and adults. During my Pediatric Infectious Diseases fellowship, I completed a Masters in Clinical Investigations that enabled me to lead pivotal studies to move the field of AMR treatment forward (e.g., piperacillin-tazobactam is associated with greater mortality than meropenem for ESBL-E infections). These studies have informed clinical guidelines and eventually led to me being the Chair of the Infectious Diseases Society of America AMR Treatment Guidance. It quickly became clear to me; however, that to effectively treat AMR infections, I needed to improve my knowledge of molecular mechanisms of resistance to develop translational treatment concepts that can be applied at the bedside. I was fortunate to receive a Career Development Award with a focus on rapid WGS to predict susceptibility testing results for clinical application. My research lab focuses on sequencing isolates and analyzing bacterial genomes to identify AMR genes and mutations in critical regions of the genome. I have been fortunate to be the PI on over $40 million in federal funds to conduct AMR research. These funds enabled me to develop a large AMR biorepository with >7,000 isolates that includes comprehensive WGS and clinical data that serves as secondary data sources for current and future mentees. Given my passion for mentoring, I have mentored dozens of trainees from graduate students to Assistant Professors in the aforementioned work. Four of my mentees have Career Development Awards and 2 are currently submitting K23/K08 awards. However, my administrative roles have grown significantly (i.e., Director of Antibiotic Stewardship and Fellowship Program Director). This makes it challenging for me to take on new mentees and is limiting my growth in research skills (particularly lab skills) which are needed to ensure I am training mentees in the most cutting edge and clinically relevant science. In my K24 proposal, I discuss plans to advance my knowledge of constructing site-directed mutants of key β- lactamase enzymes to identify amino acid residues responsible for resistance to specific β-lactams followed by molecular modelling to visualize critical amino acid substitution sites. Additionally, I would like to incorporate pharmacodynamic hollow-fiber models with drug exposures simulating humanized plasma concentrations for clinically prescribed antibiotic dosing regimens into my work to better understand the role of changes in antibiotic concentrations (e.g., dosages, infusion times, combinations) in the emergence of AMR. Furthermore, in my proposal, I outline plans to apply for additional federal funding to support mentees in two tracts of AMR research: clinical-based AMR research (e.g., K23 candidates) and laboratory-based AMR research (e.g., K08 candidates). I also discuss my specific plans to enhance my mentoring skills and my mentoring plans for trainees with support from a team of mentors, collaborators, and an external advisory committee - all of whom are internationally recognized leaders in their respective fields.