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Assistant Professor in Pediatrics and Molecular Microbiology

• Infectious Diseases
• Pathobiology
• Jeffrey S. McKinney Research Lab

Presentation Links

• Grand Rounds: Antimicrobial Resistance - Think Globally, Act Locally.
• Molecular Microbiology and Microbial Pathogenesis Bio5392 Lecture Slides: Prokaryotic Evolution I (PDF)
• Molecular Microbiology and Microbial Pathogenesis Bio5392 Lecture Slides: Prokaryotic Evolution II (PDF)

Dr. McKinney's laboratory is interested in the pathogenesis of bacterial infections and is using novel techniques of bacterial gene regulation to dissect host-pathogen interactions. The laboratory is investigating the effects of dynamically modulating virulence gene expression in E. coli and pathogenic Salmonella, using these bacteria as models of gram negative pathogens responsible for a wide range of serious infections. To modulate gene expression, the lab employs a system of inducible gene product disruption, involving RNA molecules called external guide sequences (EGSs) which target specific mRNA for cleavage by cellular RNase P.

Past work using this system to down-regulate E. coli genes essential to bacterial viability has shown the molecular and cellular effects of EGSs exhibit reproducible time course dynamics, dose-response, and synergy and are EGS oligonucleotide sequence specific. Using a new Salmonella strain allowing for the dynamic control of EGS expression triggered by various sugars, recent work focuses on genes in the Salmonella SPI-1 pathogenicity island, including the invB and invC genes involved in Salmonella's invasion of host cells. The laboratory is seeking to dissect the functions of, and dynamic interactions between, pathogenicity genes in invasion and subsequent disease.

In ongoing work, the laboratory is taking advantage of the fact that the RNase P enzyme is a ribozyme, in which RNA is catalytically active. To this end, the lab is designing new RNA molecules allowing for further analysis of the molecular mechanisms of EGS effects in Salmonella, including new molecules amenable to in vitro evolution and to studies of RNA biology in bacteria.

Potential implications of these research efforts include gaining insights to help develop new antimicrobial agents and strategies designed to counter bacterial drug resistance, and to better understand the various functions of RNA molecules in bacteria.

Education

• B.S., University of Iowa, 1986
• B.A., Oxford University, 1988
• M.D., Ph.D., University of Iowa, 1995

Training

• Resident in Pediatrics, Yale-New Haven Children's Hospital, 1996-98
• Postdoctoral Fellow, Department of Pediatrics, Division of Infectious Diseases, Yale University, 1998-2001
• Postdoctoral Fellow, Department of Molecular, Cellular, and Developmental Biology, Yale University, 1998-2001

Licensure and Board Certification

• Missouri
• American Board of Pediatrics, 1998

Honors

• National Scientific Student Research Competition Winner, 1982
• Research Presenter and U.S. Representative, London International Youth Sciences Fortnight, 1983
• Outstanding Freshman Engineer Award, University of Iowa, 1983
• Presidential Scholar, University of Iowa, 1982-1986
• Hancher Finkbine Medal (the most outstanding undergraduate), University of Iowa, 1986
• Rhodes Scholarship, Oxford University, 1986-1988
• Rhodes Trust Research Grant, Oxford and Kenya, 1987
• Midwest Universities Consortium for International Activities Grant, 1991
• Rockefeller Foundation Fellowship, 1991
• Yale Pediatrics Morris Krosnick Award (the most outstanding senior resident in pediatrics), 1998
• Pfizer Postdoctoral Fellowship Grant in Infectious Diseases, 2000-2003
• Outstanding Teaching Fellow Award, Yale-New Haven Children's Hospital, 2001
• Yale-NIH Children's Health Research Center Scholar Award, 2002-2003
• Pearson Award for Yale University Pediatric Teaching Faculty of the Year, 2003
• Washington University Digestive Disease Research Center Pilot and Feasibility Grant, 2003-2005
• Washington University Child Health Research Center Scholar Award, 2003-2004

Selected Publications

1. McKinney JS, Guerrier-Takada C, Wesolowski D, Altman S: Inhibition of Escherichia coli viability by external guide sequences complementary to two essential genes. Proc Natl Acad Sci USA 2001; 98(12):6605-10.

2. McKinney JS, Guerrier-Takada C, Galan J, Altman S: Tightly regulated gene expression system in Salmonella enterica serovar Typhimurium. J Bacteriol 2002; 184:6056-9.

3. McKinney JS, Zhang H, Kubori T, Galan JE, Altman S: Disruption of type III secretion in Salmonella enterica serovar Typhimurium by external guide sequences. Nucleic Acids Res 2004; 32(2):848-54.