Diagnosis, Treatment, and Monitoring of Polymicrobial Infections in Diabetic Wounds

Project Summary. Research: The proposed research is entitled: Diagnosis, Treatment, and Monitoring of Polymicrobial Infections in Diabetic Wounds. Diabetic wounds are prone to bacterial infections, which delay wound healing and cause severe outcomes such as amputation and sepsis. To combat wound infections, our ongoing study pinpoints

Glutamate 1-Semialdehyde (GSA), a previously underexplored bacterial metabolite in the porphyrin biosynthesis pathway. GSA can selectively induce porphyrin accumulation in bacteria but not in host cells, as the pathway is notably absent in mammals. Porphyrin accumulation causes bacteria to fluoresce and become susceptible to

blue or red light-based killing, offering a novel method to diagnose, monitor, and treat diabetic wound infections conveniently, thereby preventing catastrophic outcomes. Our substantial preliminary data have demonstrated the fluorescence imaging and killing potential of GSA-phototherapy on common wound-infecting bacteria. In this

study, we will investigate the detection thresholds, biosafety, and killing efficacy of this novel modality using diabetic mice. The translational potential of GSA-phototherapy will also be tested on diabetic mini-pigs. Our proposal offers a multifaceted solution for the timely diagnosis, real-time monitoring, and non-antibiotic treatment

of bacterial infections, addressing the critical needs in the management of chronic diabetic wounds. Mentors/Career Plan: My immediate goal is to acquire specialized training in diabetes and wound healing. To accomplish this, I have enlisted Prof. Aristidis Veves, an authority on diabetic foot ulcers, as my co-mentor. We

have identified key didactic courses and symposiums to supplement my training, and he also offers me opportunities for clinical shadowing and hands-on training with diabetic mini-pigs. In the middle of the K01 award, I aim to draft and apply for an R01 grant designed to produce a convenient GSA dressing and a phone-based

detection device that empower diabetic patients to manage their wound infections proactively and easily at home. Achieving this objective necessitates a deep understanding of photonics, fluorescence imaging, device design, and wound dressing technologies. Courses and conferences are proposed accordingly. My ultimate ambition is

to evolve into an independent investigator, focusing on pioneering bacterial-specific photomedicine for combating diabetic wound infections and promoting wound healing. Prof. Mei X. Wu, my primary mentor, has made a detailed training plan to strengthen my publication record, build my academic networking, hone my grant writing,

leadership, and transferable skills. She is deeply engaged and ensures my adherence to the timeline and, ultimately, my pathway to independence. Environment: My research will be primarily conducted in the Wellman Center for Photomedicine, in Massachusetts General Hospital (MGH) and Harvard Medical School (HMS). I will

also collaborate with Prof. Veves of Beth Israel Deaconess Medical Center (BIDMC). I have access to all essential resources at these locations and facilities. The diverse professional development resources available at MGH and HMS ensure my ability to pursue the planned study and career development goals effectively.