Diana Proctor, PhD

Areas of Interest

Research Interests

Our Mission

The Candida & Microbiome Dynamics Research Lab in the Department of Microbiology and Molecular Genetics studies the global impact, pathogenesis, and evolution of host-associated Candida species within the microbiome. Candida spp. are widely recognized as an important and growing threat to human health, particularly in underserved populations. We aim to define the mechanisms by which Candida spreads, establishes infections, and resists eradication, addressing a fundamental need in public health.

The lab employs a range of techniques, including comparative genomics, in vitro growth assays, and model systems, to explore the mycobiome and the evolution of antifungal resistance. We are committed to training the next generation of scientists who will excel in diverse careers within public health, academia, industry, and beyond. Our lab places a strong emphasis on rigorous and reproducible scientific research, while also promoting a healthy balance between work and personal life and fostering an inclusive and supportive atmosphere.

Candida spp. are a global and emerging threat

Six Candida species top the World Health Organization’s list of critical and high-priority fungal threats, with infections caused by non-albicans Candida species rising globally. Candida asymptomatically colonizes most healthy individuals as a member of the microbiome but can cause deadly infections in susceptible hosts. In fact, Candida spp. are the fourth leading cause of bloodstream infection in the United States. Additionally, the antifungals used in clinical practice are also employed in agriculture, posing unique One Health challenges, and possibly contributing to intractable fungal infections.

Using state-of-the-art methods in microbial genomics, Dr. Proctor’s research program centers on studying the ecology and evolution of Candida in diverse contexts, including humans, the environment, and agriculture. By coupling clinical and field-based studies with in vitro experimental evolution, her group strives to develop novel, ecologically informed diagnostics, therapeutics, and surveillance strategies to combat Candida infections worldwide. Our research is organized around two central themes.

Theme 1: Impact of host physiology and the microbiome and Candida colonization

One major focus of our laboratory is understanding how low salivary flow favors Candida colonization and outgrowth, building on our previous work. Patients with low salivary flow are at an increased risk of oral infection with Candida. We aim to test the hypothesis that low salivary flow selects for acidogenic and aciduric bacterial species, opening a niche for Candida colonization. Leveraging a retrospective collection of thousands of oral microbiome specimens and matched oral health records, this study investigates interkingdom interactions between fungi and bacteria before, during, and after experimental induction of low salivary flow in humans.

Through genomic analysis of approximately 10,000 human oral samples, we found that bacterial communities in the mouth vary along an ecological gradient from the front to the back of the mouth in healthy individuals with normal salivary flow. Bacteria in different oral habitats—such as supragingival surfaces, keratinized gingiva, buccal mucosa, and alveolar mucosa—show significant variation in healthy humans. In contrast, this gradient is attenuated in patients with low salivary flow, suggesting that saliva plays a crucial role in shaping species diversity across teeth. This finding is clinically significant, as it suggests bacterial biomarkers could be developed to diagnose low salivary flow, a condition often identified nine years after the first tooth is lost to disease.

Our findings have established a novel framework for understanding the ecology of the human oral microbiome. This framework prompts several key questions the group seeks to address, such as: How does the spatial organization of the bacterial component of the microbiome constrain or facilitate Candida colonization? What host factors (e.g., flow rate, salivary quality, etc.) facilitate or inhibit Candida colonization? How do microbe-microbe, including inter-kingdom interactions, influence Candida colonization?

Theme 2: Evolution of antifungal resistance

A second major focus of our laboratory is on the ecology and evolution of antifungal resistance in Candida species, particularly non-albicans Candida. Recurrent exposure to antibiotics and antifungals is common in individuals with risk factors for Candida infections (e.g., elderly, patients with diabetes, patients in the NICU) with some data suggesting prior exposure to antibiotics modifies antifungal efficacy and the evolution of fluconazole resistance. Our group replicates common clinical scenarios associated with Candida infection in vitro. Integrating culturomics with shotgun metagenomics and whole genome sequencing, my group aims to identify bacterial species from humans, the environment, and in agricultural settings that exhibit non-random interactions with Candida. Context-specific synthetic communities comprised of these species will be subjected to experimental evolution in the presence of alternating pulses of subinhibitory doses of antibiotics and antifungals. Shotgun metagenomic sequencing will be used to reconstruct the compositional and evolutionary trajectories of Candida within the microbial consortia.

By integrating clinical and field-based studies with in vitro experimental evolution, we aim to address critical questions such as: How do antifungal-resistant strains of Candida emerge and spread in and across different environments? What are the evolutionary trajectories of these resistant strains? How do these resistance elements impact the fitness and associated genomic epidemiology of Candida species within medical and agricultural settings? The long-term goals of this research are to develop strategies to mitigate the spread of resistance and inform policy on the use of antifungals in agriculture and healthcare.

Publications