Multi-Million Dollar RO1 Spotlights

Dr. José Lemos, a professor in the Department of Oral Biology, received a five-year $2,257,662 NIH R01 from the National Institute of Dental and Craniofacial Research. Dr. Lemos and his team sheds light on the potential implications for oral health and beyond. The project, “Mechanisms of metal ion homeostasis of oral Streptococci”, aims to delve deeper into characterizing the pathways that enable Streptococcus mutans (S. mutans) survival under high zinc conditions. They aim to explore the consequences of elevated zinc levels in oral biofilms, resulting from the use of zinc-containing products, on the composition of the oral microbiome.

Jose A Lemos

“Zinc is trace metal that has been used as a therapeutic agent for centuries. In oral health, zinc is incorporated into mouthwashes and toothpastes to treat halitosis and gingivitis, reduce tartar accumulation, and as an antibacterial agent to control dental plaque.”
Dr. José Lemos

In the Lemos-Abranches lab, the research team has been delving into the intricate molecular mechanisms underlying the virulence of oral pathogens. Their prior research unveiled the remarkable zinc tolerance exhibited by S. mutans, a key player in dental caries. The team identified a novel multi-metal exporter, ZccE, exclusive to S. mutans, shedding light on a potential target for antimicrobial therapy.

The multidisciplinary research team spans three colleges at the University of Florida, bringing together experts in molecular microbiology and animal models (Jacqueline Abranches and José Lemos, College of Dentistry), microbiome research (Luis Roesch, IFAS), and AI-based drug design and medicinal chemistry (Chenglong Li and Robert Huigens, College of Pharmacy). This collaborative effort seeks to develop a targeted antimicrobial therapy leveraging ZccE, ultimately aiming to selectively eliminate S. mutans from dental biofilms, thus preventing the formation of cariogenic biofilms.

The award will support the continuation of his research into the molecular factors that mediate virulence in opportunistic Gram-positive pathogens, focusing on dental pathogen S. mutans and the nosocomial pathogen Enterococcus faecalis.

Dr. Emily Bartley, an assistant professor in the Department of Community Dentistry and Behavioral Sciences, has received a five-year $2,996,203 NIH R01 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

In the project, “A multisystem resilience approach in the assessment of postsurgical pain trajectories”, aims to explore how resilience mechanisms can enhance recovery following knee and hip replacement surgeries, with the goal to understand what makes people get back to functioning normally.

Over the years, Dr. Emily Bartley has concentrated on unraveling biobehavioral and psychosocial mechanisms associated with resilience in individuals coping with persistent pain. Their research has transitioned towards viewing resilience as a central intervention target.

Emily J Bartley

This shift involves investigating how positive psychological therapies can enhance resilience and optimize pain treatment. Their work not only strives to improve post-surgical recovery but also to inform preventative measures that could transform the landscape of postsurgical pain management.

“There was limited work being done on the factors that protect people against pain and live a good life despite it.”
-Dr. Emily Bartley

Dr. Bartley’s unique perspective emerged from observing a prevailing focus on pain risk factors and exacerbating elements, prompting them to shift attention towards understanding what empowers individuals to lead fulfilling lives despite chronic pain.

The findings from this research have the potential to revolutionize clinical pain therapies. By understanding and leveraging resilience mechanisms, not only can recovery from surgeries be improved, but there is also the possibility of preventing the onset of persistent postsurgical pain. By shifting the narrative from what exacerbates pain to what promotes well-being, the research seeks to enhance the quality of life for individuals dealing with chronic pain.

Dr. Seunghee Cha, a professor in the Department of Oral Medicine, received a five-year $2,980,684 NIH R01 from the National Institute of Dental and Craniofacial Research. Dr. Cha and her team embark on a groundbreaking initiative to enhance the understanding of autoimmune Sjögren’s disease (SjD), particularly its childhood variant (cSjD) in the project “PRK sensing of mitochondrial dsRNA in childhood Sjogrens disease”.

Dr. Seunghee Cha

Dr. Cha’s research focuses on unraveling the complexities of SjD, an autoimmune condition
primarily affecting elderly females, causing severe dry mouth and dry eyes. This condition
extends beyond the typical demographic, with a recent collaboration identifying children affected
by cSjD, an area where knowledge is notably lacking.

Dr. Cha and her collaborators aim to fill this knowledge gap. In collaboration with experts from
various disciplines, the UF cSjD cohort was established four years ago. The research team has delved into molecular

analyses, focusing on the expression and roles of dsRNA helicase (SUV3) and polyribonucleotide nucleotidyltransferase (PNPase) in cSjD monocytes. Their work has highlighted alterations in these molecules, leading to mitochondrial dsRNA (mtdsRNA) accumulation in the cytoplasm, activating the protein kinase R (PKR) pathway. In addition, novel non-coding endogenous short duplex RNAs have been identified, potentially sequestering PKR from activation in healthy individuals, but being degraded in cSjD allowing PKR activation.

“Given that the UF prospective cSjD cohort at the Center for Orphaned Autoimmune Disorders (COAD) is the first in the nation, we hope that successful outcomes of this project expedite early diagnostic/prognostic biomarker discovery, the development of diagnostic criteria and personalized medicine, and the identification of natural history, prevalence, and key immune regulators in cSjD.”
-Dr. Seunghee Cha

Dr. Cha envisions a comprehensive understanding of innate immune activation by self-nucleic acids in cSjD monocytes. This knowledge will be crucial for early intervention and the development of RNA-based therapies. The team plans to conduct in-depth analyses of transcriptomic, immunological, molecular, clinical, and laboratory features of cSjD, utilizing scRNA-seq of PBMC, paired biopsy tissues, and bulk RNA-seq in addition to in vitro analyses.

Dr. Cha leads a dynamic collaborative team, which includes Co-PI Dr. Yoosik Kim, Department of Chemical and Bimolecular Engineering at KAIST, and Co-Investigators Dr. Indraneel Bhattacharyya in the Department of Oral and Maxillofacial Diagnostic Sciences, Dr. Weizhou Zhang from the College of Medicine’s Pathology department, Dr. Westley Hubbard Reeves from the Department of Rheumatology, Dr. Panayiotis Benos, Department of Epidemiology, and Dr. Akaluck Thatayatikom from Pediatric Rheumatology at AdventHealth Orlando.

As Dr. Cha and the research team embark on this ambitious journey, their work not only addresses a significant knowledge gap in autoimmune disorders but also holds the potential to transform diagnostic and therapeutic approaches for those affected by Sjögren’s disease, including the often-overlooked childhood variant.