Research
We communicate with our microbiota - the rich communities of microbes that colonize our body's surfaces - through the language of metabolic "words" or metabolites. Host-derived metabolites, or the metabolites that we as hosts make, shape the ecological balance between the good (commensal) and bad (pathogenic) bacteria in our microbiota. In turn, microbiota-derived metabolites tune our body's immune defenses. This dialogue ultimately determines our susceptibility to disease. Led by Dr. Apollo Stacy, the APOLLO (Analysis of POLymicrobial-host Language in the Oral cavity) Lab aims to decipher microbiota-host metabolic communication in the oral cavity, specifically in the settings of gum disease (periodontitis, one of the most prevalent inflammatory diseases worldwide) and its various comorbidities.
Biography
Apollo was born in the booming metropolis of Jonesboro, Arkansas, where he grew up spending most of his time in his parents’ all-you-can-eat Chinese-American buffet restaurant. In 2010, Apollo obtained his B.A. from Washington University in St. Louis, double-majoring in Biology and Earth & Planetary Sciences. From there, he joined the laboratory of Dr. Marvin Whiteley at The University of Texas at Austin, where in 2017 he received his Ph.D. in Microbiology. For his thesis, Apollo applied genomic approaches to dissect disease-promoting interactions between members of the oral microbiota. After his graduate studies, Apollo was a postdoctoral fellow in the laboratory of Dr. Yasmine Belkaid at the National Institute of Allergy & Infectious Diseases. There, he discovered a host-derived metabolite that, in response to prior infection, can “train” or enhance the ability of the gut microbiota to resist colonization by pathogens. In September 2022, Apollo became an Assistant Staff in the Cleveland Clinic Lerner Research Institute. The aim of his research group is to characterize polymicrobial-host interactions within the oral cavity that regulate susceptibility to disease.
Education & Professional Highlights
Education & Training
2006–2010 B.A. in Biology and Earth & Planetary Sciences (Washington University in St. Louis)
2010–2017 Ph.D. in Microbiology (The University of Texas at Austin)
2017–2022 Postdoctoral Fellowship (National Institute of Allergy & Infectious Diseases)
Academic Appointments
2022–now Assistant Staff, Cardiovascular & Metabolic Sciences, Lerner Research Institute
2022–now Member, Center for Microbiome & Human Health, Cleveland Clinic
2023–now Assistant Professor of Molecular Medicine, Cleveland Clinic Lerner College of Medicine
Awards
2022 Finalist for NOSTER Science Microbiome Prize
"CIMER Trained Mentor" indicates the principal investigator has completed mentorship training based on curriculum from the Center for the Improvement of Mentored Experiences in Research, aimed at advancing mentoring relationships and promoting cultural change in research.
Research
Themes
The oral microbiota is emerging as an important driver of local and systemic inflammatory disease. Like microbial communities at other body sites, the oral microbiota comprises both health- and disease-promoting microbes (commensals and pathogens). The ecological balance between these taxa - and thus host susceptibility to disease - is strongly shaped by host-derived metabolites. These molecules can directly serve as nutrients for microbial growth, and depending on the host’s immune status, they can determine the outcome of polymicrobial interactions (for example, whether commensals outcompete pathogens or vice versa).
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The long-term goal of the Apollo Stacy Lab is to translate host-derived metabolites into microbiota-directed therapies. To this end, we leverage an interdisciplinary approach involving bacterial genetics, genomics, animal models, immune profiling, and human samples. The disease that we primarily study is periodontitis, or inflammation of the tissues that support the teeth. This prevalent condition can result in tooth loss, and it also increases risk for a range of diseases in and outside the oral cavity, including oral cancer and diabetes. Projects in the lab fall under one of two themes: 1) Training commensals or 2) Targeting pathogens.
Training commensals
In response to infection, the host can increase the availability of metabolites that nourish commensals. Once “trained” by inflammation-induced metabolites, commensals can in turn enhance host resistance to subsequent infection. While this phenomenon was first described in the gut, we hypothesize that it also occurs in response to inflammation at other barrier sites, such as periodontitis in the oral cavity. Current projects are focused on nitrate, a periodontitis-induced host metabolite that can elicit oral commensals by acting as an electron acceptor. We are exploring whether host and/or dietary nitrate can mitigate periodontitis by promoting commensals over pathogens.
Targeting pathogens
Unchecked inflammation can generate metabolites that favor the outgrowth of pathogens. Preventing pathogens from exploiting such metabolites may represent a more targeted approach for treating microbiota-driven diseases, in contrast to antibiotics which also kill commensals. Current projects are focused on the microbiota-derived metabolite formate, the production of which we hypothesize is stimulated by inflammation-induced hypoxia. To exploit formate, pathogens require the micronutrient selenium. Based on this, we are exploring whether depleting selenium can mitigate periodontitis by targeting pathogen formate metabolism. We are also developing an interest in defining the metabolites that pathogens exploit in the setting of oral squamous cell carcinoma and diabetes.
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Our Team
Selected Publications
View publications for Apollo Stacy, PhD
(Disclaimer: This search is powered by PubMed, a service of the U.S. National Library of Medicine. PubMed is a third-party website with no affiliation with Cleveland Clinic.)
Selected Publications
Infection-elicited microbiota promotes host adaptation to nutrient restriction
De Siqueira MK, Andrade-Oliveira V, Stacy A*, Guimarães JPT, Alberca-Custodio RW, Castoldi A, Santos JM, Davoli-Ferreira M, Menezes-Silva L, Turato WM, Han S-J, Zaretsky AG, Hand TW, Câmara NOS, Russo M, Jancar S, da Fonseca DM*, Belkaid Y*
*Co-corresponding author
PNAS | 2023
Remembrance of infections past
Stacy A
Science | 2022
Infection trains the host for microbiota-enhanced resistance to pathogens
Stacy A*, Andrade-Oliveira V, McCulloch JA, Hild B, Oh JH, Perez-Chaparro PJ, Sim CK, Lim AI, Link VM, Enamorado M, Trinchieri G, Segre JA, Rehermann B, Belkaid Y*
*Co-corresponding author
Cell | 2021
Large-scale identification of pathogen essential genes during coinfection with sympatric and allopatric microbes
Lewin GR, Stacy A, Michie KL, Lamont RJ, Whiteley M
PNAS | 2019
Defining genetic fitness determinants and creating genomic resources for an oral pathogen
Narayanan AM, Ramsey MM, Stacy A*, Whiteley M*
*Co-corresponding author
Applied and Environmental Microbiology | 2017
Co-infecting microbes dramatically alter pathogen gene essentiality during polymicrobial infection
Ibberson CB, Stacy A, Fleming D, Dees JL, Rumbaugh K, Gilmore MS, Whiteley M
Nature Microbiology | 2017
A commensal bacterium promotes virulence of an opportunistic pathogen via cross-respiration
Stacy A, Fleming D, Lamont RJ, Rumbaugh KP, Whiteley M
mBio | 2016
Microbial community composition impacts pathogen iron availability during polymicrobial infection
Stacy A, Abraham N, Jorth P, Whiteley M
PLOS Pathogens | 2016
The biogeography of polymicrobial infection
Stacy A, McNally L, Darch SE, Brown SP, Whiteley M
Nature Reviews Microbiology | 2016
Bacterial fight-and-flight responses enhance virulence in a polymicrobial infection
Stacy A, Everett J, Jorth P, Trivedi U, Rumbaugh KP, Whiteley M
PNAS | 2014
Careers
We currently have openings for postdocs and graduate students.
We are looking for motivated individuals who share our enthusiasm for polymicrobial-host interactions, particularly bacterial metabolism, genomics, and/or barrier immunity. Individuals of all backgrounds are welcome to apply, but especially those who are willing to help build a collegial environment that fosters scientific curiosity, rigor, and growth.
Prospective postdocs should email Apollo ([email protected]) their CV, a brief description (<1 page) of their research interests and career goals, and contact info for 3 references.
Interested graduate students should email Apollo ([email protected]) to discuss potential rotation projects. The lab can (or will soon be able to) accept students from Case Western Reserve University, Cleveland State University, and Kent State University.
Come join our team and enjoy all that the Cleveland Clinic and the city of Cleveland have to offer!
Research News
Dr. Toney joins Multidisciplinary Achievement in Respiratory Research Training (SMARRT) program