The proposed K22 career development plan will allow Dr. Janina P. Lewis to complete a year of advanced postdoctoral training, and then transition into a tenure-track assistant professorship in VCU Philips Institute of Oral and Craniofacial Molecular Biology. A major portion of the scholar development phase will be spent taking formal courses in biophysical techniques and gaining hands-on experience in mass spectroscopy, X-ray crystallography, and computer-based molecular modeling. This training will take place in the VCU Department of Chemistry and the VCU Institute for Structural Biology and Drug Design. Upon taking her place in the faculty ranks at the VCU Philips Institute, Dr. Lewis will be well positioned to pursue new avenues for studying virulence factors in the periodontal pathogen, Porphyromonas gingivalis. To date her research has centered on the lysine-specific protease, Kgp. She has determined that Kgp is indispensable in the process of accumulation of hemin on the surface of the bacteria. Although hemin profoundly affects virulence of P. gingivalis, the mechanisms involved in its uptake and its role in genetic regulation are poorly understood. Accomplishment of the aims of this proposal will advance the knowledge of P. gingivalis on two fronts. First, it shall deepen our knowledge about the secretion of, physical and structural properties of Kgp. Second, she shall build on her observations that proteins other than Kgp are involved in hemin and iron uptake, and that global regulatory networks control expression. The results of this work will help define hemin uptake factors and regulatory elements that may be future targets of antiperiodontitis strategies. The intellectual and instrumentation training resources coupled with the institution's commitment to Dr. Lewis' faculty development provides a highly supportive environment for a successful transition to the faculty phase of this award, and bodes well for her rapid development as an independent investigator.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Career Transition Award (K22)
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NIDCR Special Grants Review Committee (DSR)
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Hardwick, Kevin S
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Virginia Commonwealth University
Schools of Dentistry
United States
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Lewis, Janina P; Yanamandra, Sai S; Anaya-Bergman, Cecilia (2012) HcpR of Porphyromonas gingivalis is required for growth under nitrosative stress and survival within host cells. Infect Immun 80:3319-31
Lewis, Janina P (2010) Metal uptake in host-pathogen interactions: role of iron in Porphyromonas gingivalis interactions with host organisms. Periodontol 2000 52:94-116
Anaya-Bergman, Cecilia; He, Jia; Jones, Kevin et al. (2010) Porphyromonas gingivalis ferrous iron transporter FeoB1 influences sensitivity to oxidative stress. Infect Immun 78:688-96
Anaya, Cecilia; Church, Nadia; Lewis, Janina P (2007) Detection and identification of bacterial cell surface proteins by fluorescent labeling. Proteomics 7:215-9
Lewis, Janina P; Plata, Konrad; Yu, Fan et al. (2006) Transcriptional organization, regulation and role of the Porphyromonas gingivalis W83 hmu haemin-uptake locus. Microbiology 152:3367-82
He, Jia; Miyazaki, Hiroshi; Anaya, Cecilia et al. (2006) Role of Porphyromonas gingivalis FeoB2 in metal uptake and oxidative stress protection. Infect Immun 74:4214-23
Zhang, Ping; Yang, Qiu-Bo; Balkovetz, Daniel F et al. (2005) Effectiveness of the B subunit of cholera toxin in potentiating immune responses to the recombinant hemagglutinin/adhesin domain of the gingipain Kgp from Porphyromonas gingivalis. Vaccine 23:4734-44
Califano, Joseph V; Chou, Debra; Lewis, Janina P et al. (2004) Antibody reactive with Porphyromonas gingivalis hemagglutinin in chronic and generalized aggressive periodontitis. J Periodontal Res 39:263-8