Phone: (352) 392-3791
- Professor, Physiology & Functional Genomics, College of Medicine
- Professor (affiliate), Department of Medicine, Div. of Gastroenterology, College of Medicine
- Professor (affiliate), Department of Surgery, College of Medicine
- Professor (affiliate), Department of Psychiatry, College of Medicine
- Professor (affiliate), Center for Exercise Science, College of Health & Human Performance
- Professor (affiliate), Department of Entomology & Nematology, University of Florida
Research in the laboratory of Bruce R. Stevens centers on the plasma membrane transport of organic solutes and inorganic ions, and intermediary metabolism of these molecules by epithelial cells and brain cells. The cellular physiology, molecular biology, and regulation of transport and metabolism is pursued, along with the roles transporters play in regulating inflammatory events. This research is pursued in 5 focal areas.
- Amino acid transporter B0AT1 interaction with coronavirus SARS-CoV-2 receptor ACE2 in COVID‑19.
My laboratory originally discovered and functionally characterized B0AT1 as a key protein that was utilized by Pfizer-BioNTech as crucial to their successful development of the country’s first publicly deployed COVID-19 vaccine. The body makes this B0AT1 in order to stabilize the ACE2 receptor in cell membranes. Other labs assigned B0AT1 to the SLC6A19 gene. This receptor is hijacked by the COVID-19 coronavirus as its infection launch point. Our work uncovered the mechanism of a functional property that this arrangement regulates nutrient amino acid absorption by cells of the gut. The gastrointestinal tract is the body’s greatest concentration of such receptors for COVID-19 virus, and notably about half of COVID-19 patients suffer gastrointestinal symptoms and shed virus in stool. Among our techniques is novel use of a high-energy electron linear accelerator. We are pursuing a similar mechanism exhibited by the glycine and proline transporter IMINO which our lab also originally discovered and functionally characterized in intestinal epithelial membranes. Our findings contribute to development of novel treatments for COVID-19 variant outbreaks and the persistence of gastrointestinal symptoms experienced in “long-haul COVID-19”, with implications to guide hygiene policy decisions.
- Gut Microbiome-Brain role in mental illnesses and hypertension.
Based on our human clinical studies of gut microbiome metagenomics and correlations with patient blood inflammation metabolomics, I have developed a model for the role of intestinal dysbiosis in mood disorders that are comorbid with cardiovascular disease. Multivariate analyses of microbial genomic data are analyzed using a unique machine-learning artificial intelligence (AI) software algorithm that we developed. Additionally, my lab made initial discoveries and functional characterization of key components of the intestinal epithelium manifestation of the local gut Renin-Angiotensin-System (RAS), which is modulated by bioactive dietary digestion products and gut bacterial metabolism. My long-term goal in this arena is to ascertain an optimal gut microbiota ecosystem that shapes healthy cardiovascular and brain functions.
- Mechanisms of neuropathy in major mental illnesses—retrovirus models of double-stranded RNA effects on innate immunity of brain cells, via TLR3 signaling in microglia and astrocytes.
Using a model of inflammatory neuropathy, my lab has utilized cultured brain microglia, astrocytes, neurons, and lymphocytes to uncover the role of dsRNA in brain cell signaling PKR, eIF2-a, NF-kB, and Nrf2 control of neural amino acid transporters (including monomeric isoforms, splice variants, and heterodimer subunits) as rate-limiting steps in gene expression of biosynthesis of glutathione, nitric oxide, amino acid neuromodulators, and triggering of cytokines. These studies have formed the foundation for related work coming out of other labs.
- Cloning and site-directed mutagenesis functional characterization of amino acid transporter genes of Aedes aegypti as targets for novel insecticides to mitigate mosquito-vector diseases such as Zika, West Nile, Yellow Fever.
My lab cloned the first gene encoding a new multifunctional protein family in mosquitos. Our cloned CAATCH1 gene encodes a midgut epithelium proline transporter that also functions independently as an amino acid ligand-gated cation channel. We demonstrated that these mechanisms are thermodynamic uncoupled by the presence of methionine. This led us to develop environmentally safe methionine-based larvicides that are highly lethal to both Aedes aegypti and Aedes albopictus vectors of Zika virus. We were awarded US patents #6,766,613 and #7,181,884 for this work.
- Skeletal muscle function affected by intermediary metabolism of amino acid metabolism in splanchnic circulation, with autoimmune and neuroendocrine changes.
Based on clinical studies in humans, we developed an oral intervention comprised of ketoacid deriviatives of branched chain amino acids that augments performance parameters of exercising skeletal muscle. After being awarded U.S. patent #6,100,287 for the IND prototype, the resulting commercial product has been continually licensed during the past 14 years. Additional collaborative studies with NASA concerned microgravity effects on muscle function.
Teaching (Including Courses)
- Human Physiology in Translation (BMS 3521)
- Principles of Physiology (GMS 6400C)
- Fundamentals of Gastrointestinal Physiology (GMS 6415)
- Fundamentals of Medical Physiology (GMS 6440)
- Fundamentals of Physiology and Functional Genomics 3 (GMS 6473)
- Medical Gastrointestinal Physiology (GMS 6479)
- Gastroenterology and Hepatology (BMS 6634)
- Dental Physiology (DEN 5120C)
- Human Physiology for Physician Assistants (PAS 5025)
Awards and Honors
- 2018, 2019, & 2020: Exemplary Teacher Award, University of Florida College of Medicine
- 2013: Basic Science Teacher of the Year, University of Florida College of Medicine
- U.S. Patent No. 6,100,287: “Materials and methods for enhancing muscle performance and recovery from fatigue.”
- U.S. Patent No. 6,766,613: “Materials and methods for controlling pests.”
- U.S. Patent No. 7,181,884: “Materials and methods for controlling medical insect vector pests.”
- Stevens, B. R., Ellory, J. C., & Preston, R. L. (2021). B0AT1 amino acid transporter complexed with SARS-CoV-2 receptor ACE2 forms a heterodimer functional unit: in situ conformation using radiation inactivation analysis. Function (Oxf), 13 May 2021:2(4). https://doi.org/10.1093/function/zqab027 . PMCID: PMC8194517
- Stevens, B. R., Pepine, C. J., Richards, E. M., Seungbum, K., & Raizada, M. K. (2021). Depressive hypertension: A proposed human endotype of brain/gut microbiome dysbiosis. Am. Heart J. https://doi.org/10.1016/j.ahj.2021.05.002 . (PMID 33984318)
- Prasad, R., Patton, M. J., Floyd, J. L., Vieira, C. P., Fortmann, S., DuPont, M., Harbour, A., Jeremy, C. S., Wright, Lamendella, R., Stevens, B. R., & Grant, M. B. (2021). Plasma microbiome in COVID-19 subjects: an indicator of gut barrier defects and dysbiosis. bioRxiv 2021: https://doi.org/10.1101/2021.04.06.438634 .
- Stevens, B. R. (2020). TMPRSS2 and ADAM17 interactions with ACE2 complexed with SARS-CoV-2 and B0AT1 putatively in intestine, cardiomyocytes, and kidney. bioRxiv. 2020 November: 1-21. https://doi.org/10.1101/2020.10.31.363473
- Andring, J.T., KcKenna, R., & Stevens, B. R. (2020). Amino acid transporter B0AT1 influence on ADAM17 interactions with SARS-CoV-2 receptor ACE2 putatively expressed in intestine, kidney, and cardiomyocytes. bioRxiv. 2020 October; 1-12, https://doi.org/10.1101/2020.10.30.361873
- Li, J., Stevens, B. R., Richards, E. M., & Raizada, M. K. (2020). SARS-CoV-2 Receptor ACE2 (Angiotensin-Converting Enzyme 2) Is Upregulated in Colonic Organoids From Hypertensive Rats. Hypertension, 76(3),e26-e28. https://doi.org/10.1161/HYPERTENSIONAHA.120.15725 . Epub 2020 Jul 9. (PMID: 32643416)
- Sharma, R. K., Stevens, B. R., Obukhov, A. G., Grant, M. B., Oudit, G. Y., Li, Q., Richards, E. M., Pepine, C. J., & Raizada, M. K. (2020). ACE2 (Angiotensin-Converting Enzyme 2) in Cardiopulmonary Diseases: Ramifications for the Control of SARS-CoV-2. Hypertension, 76(3), 651-661. doi: 10.1161/HYPERTENSIONAHA.120.15595. Epub 2020 Aug 12. Review. (PMCID: PMC7430041)
- Obukhov, A. G., Stevens, B. R., Prasad, R., Li, Calzi, S., Boulton, M. E., Raizada, M. K., Oudit, G. Y., & Grant, M.B. (2020). SARS-CoV-2 Infections and ACE2: Clinical Outcomes Linked With Increased Morbidity and Mortality in Individuals With Diabetes. Diabetes, 69(9), 1875-1886. doi: 10.2337/dbi20-0019. Epub 2020 Jul 15. (PMCID: PMC7458035)
- Stevens, B. R., Roesch, L., Thiago, P., Russell, J. T., Pepine, C. J., Holbert, R. C., Raizada, M. K., & Triplett, E. W. (2020). Depression phenotype identified by using single nucleotide exact amplicon sequence variants of the human gut microbiome. Nature Molecular Psychiatry, Jan 27. doi: 10.1038/s41380-020-0652-5. (PMID: 31988436)
- Nakai, M., Ribeiro, R. V., Stevens, B. R., Gill, P., Muralitharan, R. R., Yiallourou, S., Muir, J., Carrington, M., Heal, G. A., Kaye, D. M., & Marques, F. Z. (2021). Essential hypertension is associated with changes in gut microbial metabolic pathways: A multi-site analysis of ambulatory blood pressure. Hypertension. 2021 Aug 2:HYPERTENSIONAHA12117288. https://doi.org/10.1161/HYPERTENSIONAHA.121.17288 Epub ahead of print. (PMID: 34333988)
- Weeks, E. N. I., Kroll, K. J., Johnson, T. S., Colquhoun, T., Cuda, J. P., Denslow, N. D., & Stevens, B. R. (2021). Novel effective mosquito larvicide DL-methionine: lack of toxicity to non-target aquatic organisms. Ecotox. Environ. Safety. https://doi.org/10.1016/j.ecoenv.2021.112013
- Stevens, B. R., Goel, R., Seungbum, K., Richards, E. M., Holbert, R. C., Pepine, C. J., & Raizada, M. K. (2017). Increased human intestinal barrier permeability plasma biomarkers zonulin and FABP2 correlated with plasma LPS and altered gut microbiome in anxiety or depression. Gut BMJ, Aug; 67(8):1555-1557. (PMCID: PMC5851874)