Ph.D., University of Miami School of Medicine
Postdoc, Harvard Medical School
Research in my lab is focused on understanding the factors that determine host susceptibility or resistance to infection with the intracellular bacterial pathogen Listeria monocytogenes. We use a variety of bacteriologic and immunologic approaches to study the complex interplay between the virulence strategies of the pathogen and the protective immune responses of the host.
L. monocytogenes are Gram-positive bacteria that cause foodborne illness after ingestion of contaminated “ready-to-eat” foods such as deli meats, unpasteurized cheeses or processed produce. The high fatality rate (~30%) for systemic listeriosis makes it a significant public health concern for high-risk groups including neonates, pregnant women, and people in other categories (the elderly, transplant recipients, other immune comprised people with chronic diseases) that are steadily increasing in number due to medical advances.
We recently developed a novel mouse model for oral transmission of L. monocytogenes that closely mimics all phases of human disease: (1) ingestion of contaminated food, (2) a distinct gastrointestinal infection phase followed by (3) varying degrees of systemic spread in susceptible vs. resistant mouse strains, and (4) late stage spread to the brain. We are currently using this model to understand how L. monocytogenes colonize the colon and then disseminate to peripheral tissues.
We have two projects funded by NIAID that use this model: 1) to identify the intracellular growth niches for L. monocytogenes in the ileum and colon and determine the role that cytosolic invasion plays in dissemination to other tissues and 2) to explore the possibility that neurotropic strains of L. monocytogenes can spread directly to the brain via axonal migration without reaching high titer in the blood.
Dr. D'Orazio was one of three faculty members across the entire UK campus who was honored with a 2020 Excellent Undergraduate Research Mentor Award.
Dr. D'Orazio was awarded a new R21 grant "Defining the Intracellular Growth Niche of Foodborne Listeria monocytogenes on March 01. 2020.
Dr. D'Orazio will be an invited speaker at the International Symposium on Problems of Listeriosis to be held in Toronto September 24-27, 2019. ISOPOL is a meeting that has been held every three years since 1957 in various countries across the globe and brings together experts in epidemiology, diagnostics, genomics and pathogenesis.
Undergraduates Taylor Senay and Katie Alexander presented a poster entitled "Neurotropic strains of Listeria monocytogenes disseminate to the brain without reaching high titer in the blood" at the American Society for Microbiology Microbe Conference in San Francisco, CA on June 20-24, 2019.
Dr. D'Orazio was nominated as "A Teacher Who Made a Difference" on April 27, 2019.
Senay TE, Ferrell JL, Garrett FG, Albrecht TA, Myers-Morales T, Alexander K, Grothaus OF, Cho J and D'Orazio SEF. Neurotropic lineage III strains of Listeria monocytogenes disseminate to the brain without reaching high titer in the blood. mSphere (in revision).
Pitts, MG and D’Orazio, SEF. (2019) Prostaglandin E2 inhibits the ability of neutrophils to kill Listeria monocytogenes. J. Immunol. 202(12):3474-3482. [https://www-jimmunol-org.ezproxy.uky.edu/content/202/12/3474.long]
Light SH, Meheust R, Ferrell JL, Cho J, Deng D, Agostoni M, Iavarone M, Banfield JF, D'Orazio SEF, and Portnoy DA. (2019) Extracellular electron transfer powers flavinylated extracellular reductases in Gram-positive bacteria. PNAS 116(52):26892-9.
Imperiale MJ, Blader I, Bradford P, D’Orazio S, Duprex WP, Ellermeier CD, Fernandez-Sesma A, McMahon K, Mitchell A, Pasetti MF, and Tringe S. (2019) mSphere of Influence: the view from the microbiologists of the future. mSphere. 4(3):e00348-19.
D'Orazio, SEF. (2019) Innate and Adaptive Immune Responses during Listeria monocytogenes infection. Microbiol. Spectr. 7(3): doi:1128. [https://www-asmscience-org.ezproxy.uky.edu/content/journal/microbiolspec...
Pitts MG, Combs T, and D’Orazio SEF.(2018) Neutrophils from both susceptible and resistant mice efficiently kill opsonized Listeria monocytogenes. Infect. Immun. 86(4):e00085-18.
Pitts, MG and D’Orazio, SEF. (2018) A comparison of oral and intravenous mouse models of listeriosis. Pathogens. 7(1): 13.
Schardt J, Jones GS, Mueller-Herbst S, D’Orazio SEF, and Fuchs TM. (2017) Comparison between Listeriasensu strictuand Listeria sensu latostrains identifies novel determinants involved in infection. Sci. Rep. 7(1):17821. doi:10.1038/s41598-017-17570-0
Jones GS, Smith V, and D’Orazio SEF. (2017) Listeria monocytogenes replicate in bone marrow-derived CD11c+ cells, but not in dendritic cells isolated from the urine gastrointestinal tract. J. Immunol. 199(11): 3789-3797.
Jones, G.S. and S.E.F. D'Orazio. (2017) Monocytes are the predominant cell type associated with Listeria monocytogenes in the gut, but they do not serve as an intracellular growth niche. J. Immunol. doi: 10.4049
Pitts, M.G., T. Myers-Morales, and S.E.F. D'Orazio. (2016) Type I IFN does not promote susceptibility to foodborne Listeria monocytogenes. J. Immunol. 196(7): 3109-16 [http://www.ncbi.nlm.nih.gov/pubmed/?term=26895837]
Jones, G.S., K.M. Bussell, T. Myers-Morales, A.M. Fieldhouse, E.N. Bou Ghanem, and S.E.F. D'Orazio. (2015) Intracellular Listeria monocytogenes comprise a minimal but vital fraction of th intestinal burden following foodborne infection. Infect. Immun. 83(8):3146-56. [http://www.ncbi.nlm.nih.gov/pubmed/26015479]
Chen, L-H, V.K. Koseoglu, Z.T. Guvener, T. Myers-Morales, J.M. Reed, S.E.F. D'Orazio, K.W. Miller, and M. Gomelsky. (2014) Cyclic di-GMP-dependent signaling pathways in the pathogenic firmicute Listeria monocytogenes. PLoS Pathogens. 10(8):e1004301.[http://www.ncbi.nlm.nih.gov/pubmed/25101646].
D'Orazio, S.E.F. (2014) Animal models for oral transmission of Listeria monocytogenes. Front. Cell Infect. Microbiol. 4:15 doi: 10.3389/fcimb [http://www.ncbi.nlm.nih.gov/pubmed/24575393]
Myers-Morales, T., K.M. Bussell, and S.E.F. D'Orazio. (2013) Fecal transplantation does not transfer either susceptibility or resistance to food borne listeriosis in C57BL/6 and BALB/c/By mice. F1000 Res. 2:177. [http://www.ncbi.nlm.nih.gov/pubmed/24555086]
Bou Ghanem, E.N., G.S. Jones, T. Myers-Morales, P.D. Patil, A.N. Hidayatullah, and S.E.F. D'Orazio. (2012) InlA promotes dissemination of Listeria monocytogenes to the mesenteric lymph nodes during food borne infection of mice. PLoS Pathogens. 8(11):e1003015. [http://www.ncbi.nlm.nih.gov/pubmed/23166492]
Bou Ghanem, EN and S.E.F. D'Orazio. (2011) Human CD8+ T cells display a differential ability to undergo cytokine-driven bystander activation. Cell. Immunol. 272(1):79-86. [http://www.ncbi.nlm.nih.gov/pubmed/21978649]
Bou Ghanem, E.N., C. C. Nelson and S.E.F. D’Orazio. (2011) T cell intrinsic factors contribute to the differential ability of CD8+ T cells to rapidly secrete IFNg in the absence of antigen. J. Immunol. 186(3):1703-12 [Abstract]
Murapa, P., M. R. Ward, S. K. Ghandhapudi, J. G. Woodward and S.E.F. D’Orazio. (2011) HSF-1 protects mice from rapid death during Listeria monocytogenes infection by regulating production of TNFa during fever. Infect. Immun. 79(1): 177-184. [Abstract]