Frank R. DeLeo, Ph.D.

Acting Chief, Laboratory of Human Bacterial Pathogenesis
Chief, Pathogen-Host Cell Biology Section

Senior Investigator

Dr. DeLeo received his Ph.D. in microbiology from Montana State University in 1996, studying the molecular basis of superoxide generation by human neutrophils. He did his postdoctoral training in the area of innate immunity and infectious disease in the department of medicine at the University of Iowa (1996-2000). Dr. DeLeo joined the staff at Rocky Mountain Laboratories in 2000. He serves currently on the editorial board of the Journal of Immunology.

Description of Research Program

Community MRSA (red) causes destruction of human neutrophils (neutrophil debris, yellow).

Although most bacteria are killed readily by neutrophils, pathogens such as Staphylococcus aureus have evolved mechanisms to circumvent destruction by these key innate immune cells and thereby cause human infections. Therefore, a better understanding of the bacteria-neutrophil interface at the cell and molecular levels will provide information critical to our understanding, treatment, and control of disease caused by bacterial pathogens.

The long-term objective of our research is to promote development of enhanced diagnostics, better prophylactic agents, and new treatments for emerging infectious pathogens such as community-associated (or -acquired) methicillin-resistant S. aureus (CA-MRSA). To achieve that objective, the Pathogen-Host Cell Biology Section does the following:

1. Conducts a systematic molecular dissection of steps involved in the pathogen-host interaction, with specific emphasis on the interaction of bacterial pathogens with human neutrophils
2. Investigates mechanisms mediating evasion of innate immunity by pathogens of special interest such as Staphylococcus aureus
3. Identifies new virulence genes involved in the pathogenesis of infections caused by pathogens of special interest
4. Utilizes appropriate ex vivo assays, animal models (including knock-out mice), and (if possible) human specimens to test hypotheses developed from in vitro analyses

Major Areas of Research

• Neutrophil biology and function
• Neutrophil–bacteria interactions, with special emphasis on the interaction of MRSA and human neutrophils
• Staphylococcus aureus virulence mechanisms
• Clinically-related research performed in collaboration with DIR laboratories in Bethesda, MD, including the Laboratory of Clinical Infectious Diseases and the Laboratory of Host Defenses

Research Group Members

Adam D. Kennedy, Ph.D., Amy M. Palazzolo-Ballance, Ph.D., Christy Ventura, Ph.D., Shawna F. Graves, Kevin R. Braughton, Adeline R. Whitney, and Bradley Hoe.

Selected Publications

(View list in PubMed)

Kennedy AD, Otto M, Braughton KR, Whitney AR, Chen L, Mathema B, Mediavilla JR, Byrne KA, Parkins LD, Tenover FC, Kreiswirth BN, Musser JM, DeLeo FR. Epidemic community-associated methicillin-resistant Staphylococcus aureus: recent clonal expansion and diversification. Proc Natl Acad Sci USA. 2008 Jan 29;105(4):1327-32.

Palazzolo-Ballance AM, Reniere ML, Braughton KR, Sturdevant DE, Otto M, Kreiswirth BN, Skaar EP, DeLeo FR. Neutrophil microbicides induce a pathogen survival response in community-associated methicillin-resistant Staphylococcus aureus. J Immunol. 2008 Jan 1;180(1):500-9.

Burlak C, Hammer CH, Robinson MA, Whitney AR, McGavin MJ, Kreiswirth BN, DeLeo FR. Global analysis of community-associated methicillin-resistant Staphylococcus aureus exoproteins reveals molecules produced in vitro and during infection. Cell Microbiol. 2007 May;9(5):1172-90.

Voyich JM, Otto M, Mathema B, Braughton KR, Whitney AR, Welty D, Long RD, Dorward DW, Gardner DJ, Lina G, Kreiswirth BN, DeLeo FR. Is Panton-Valentine leukocidin the major virulence determinant in community-associated methicillin-resistant Staphylococcus aureus disease? J Infect Dis. 2006 Dec 15;194(12):1761-70.

Kobayashi SD, Braughton KR, Whitney AR, Voyich JM, Schwan TG, Musser JM, DeLeo FR. Bacterial pathogens modulate an apoptosis differentiation program in human neutrophils. Proc Natl Acad Sci USA. 2003 Sep 16;100(19):10948-53.

Kobayashi SD, Voyich JM, Buhl CL, Stahl RM, DeLeo FR. Global changes in gene expression by human polymorphonuclear leukocytes during receptor-mediated phagocytosis: cell fate is regulated at the level of gene expression. Proc Natl Acad Sci USA. 2002 May 14;99(10):6901-6.

Data in Public Repositories (selected)

Microarray data for Voyich et al., 2005. J Immunol. 175: 3907-3919, are posted on the Gene Expression Omnibus as data series GSE1550.

Microarray data for Kobayashi et al., 2004. J Immunol. 172: 636-643, are posted on the Gene Expression Omnibus as data series GSE935.

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