Roger Rank

Immunology/Bacteriology

Research Interest:  Immunology and pathogenesis of infections with Chlamydia

Ph.D. Hahnemann University

Phone: (501) 364-2474
Fax: (501) 364-2403

E-mail   

Research Description

Chlamydia trachomatis is the leading cause of sexually transmitted disease in the United States and Europe , with roughly 10% of the sexually active population infected. The organism produces a urethritis in males and cervicitis in women. Generally, the infection is asymptomatic in the female. While the primary target in female is the cervix, the organism may move up the genital tract and infect the fallopian tubes, producing salpingitis or pelvic inflammatory disease. The consequences of fallopian tube infection may be the development of scar tissue which can lead to tubal obstruction and infertility. In addition, C. trachomatis is the causative agent of trachoma, the leading cause of preventable blindness in the world.

Our group has maintained an active and funded research program on the study of chlamydial infections for the last 30 years. During this time, we initially developed and characterized the guinea pig and mouse models for chlamydial genital infection and subsequently employed those models to describe the basic adaptive immune mechanisms elicited by the infection. In our studies, we have established an essential role for both antibody and cellular immune mechanisms in resolution of and resistance to genital disease and characterized those responses in the genital tract. While the vast majority of that work investigated the responses in the female, we have initiated and are conducting studies on the host response to chlamydial infection in the male genital tract. In addition, it is apparent that infection acquired by the female from the male by sexual transmission results in a shorter infection course, suggesting that there are factors involved in the male which can affect the response in the female.

While the host response is involved in a protective immune response, it is also patently clear that chlamydial disease is also caused by the host response. The current hypothesis is that both the acute inflammatory response and the T cell response play important roles in the production of disease. Therefore, the major goal of our research program currently is to understand the basic mechanisms of disease in both the genital tract and eye.

Using our animal models, we now have the ability to examine and define the molecular and cellular mechanisms in vivo that are initiated by infection and lead to the overall pathologic response. We have found that neutrophils enter the infected epithelium within 6 hours of infection, well before the organism has completed one cycle of replication which takes about 24 hours. We are currently using molecular and cellular techniques to define the molecular mechanisms by which chlamydiae initiate the production of chemokines which result in the production of the inflammatory reaction. We are also examining the exact cellular and molecular mechanisms by which neutrophils damage the local epithelium and how they may influence the development of the adaptive immune response, all within the first 24 hours of infection. These studies will lead to exciting new concepts on the host-pathogen interaction at its most basic level.

References

Rank, R.G. The CD4 Response. In Chlamydia: Genomics, Pathogenesis and Implications for Control , Bavoil, P. and Wyrick, P. (eds). Horizon Bioscience, Norfolk , U.K. 2006.

Burall, L.S., Liu, Z., Rank, R., Bavoil, P.M. The chlamydial invasion-like protein gene conundrum. Microbes and Infection 9: 873-880, 2007.

Nagarajan, U.M., Ojcius, D.M., Stahl, L., Rank, R.G., Darville, T. Chlamydia trachomatis Induces Expression of IFN-{gamma}-Inducible Protein10 and IFN-{beta} Independent of TLR2 and TLR4, but Largely Dependent on MyD88. J. Immunol.175: 450-460, 2005.

Nagarajan, U. M., O'Connell, C., Rank, R.G. Molecular characterization of guinea pig ( Cavia porcellus ) CD8? and CD8? cDNA. Tissue Antigens 63:184-189, 2004.

Rank, R.G., Bowlin, A.K., Reed, R., Darville, T. Characterization of chlamydial genital infection resulting from sexual transmission from male to female guinea pigs and determination of infectious dose. Infect. Immun., 71:6148-6154, 2003.

Perfettini, J-L., Ojcius, D.M., Andrews, C.W., Korsmeyer, S.J., Rank, R.G. , Darville, T. Role of proapoptotic BAX in propagation of Chlamydia muridarum (the mouse pneumonitis strain of Chlamydia trachomatis ) and the host inflammatory response. J. Biol. Chem. 278:  9496-9502, 2003.

Read T.D., Myers G.S.A., Brunham R.C., Nelson W.C., Paulsen I.T., Heidelberg J., Holtzapple E., Khouri H., Federova N.B., Carty H.A., Umayam L.A., Haft D.H., Peterson J.1, Beanan M.J.1, White O.1, Salzberg S.L., Hsia R.-c., McClarty G., Rank R.G., Bavoil P.M. and Fraser C.M. Genome sequence of Chlamydophila caviae ( Chlamydia  psittaci GPIC): examining the role of biotype-specific genes in the evolution of the chlamydiaceae. Nucleic Acids Research 31:2134-2147, 2003.

Perfettine, J-L, Darville, T., Daultry-Varsat, A., Rank, R.G., Ojcius, D.M. Inhibition of apoptosis by IFN-gamma in cells and mice infected with Chlamydia trachomatis . 2002. Infect. Immun. 70:2559-2565.

Darville, T., Andrews, C.W., Sikes, J.D., Fraley, P.L., Rank, R.G. 2001. Early local cytokine profiles in strains of mice with different outcomes from chlamydial genital tract infection. Infect. Immun. 69:3556-3561.

Hawkins, R. A., Rank, R.G., and Kelly, K.A. 2000. Expression of mucosal homing receptor a 4 b 7 is associated with enhanced migration to the Chlamydia -infected murine genital mucosa iIn vivo. Infect. Immun. 68: 5587-5594.

Kelly, K.A., Walker , J.C., Jameel, S.H., Gray, H.L., Rank, R.G. 2000. Differential regulation of CD4 lymphocyte recruitment between the upper and lower regions of the genital tract during Chlamydia infection. Infect. Immun. 68:1519-1528.

Rank, R.G., Bowlin, A.K., Kelly, K.A. 2000. Characterization of the lymphocyte response in the female genital tract during ascending chlamydial genital infection in the guinea pig model. Infect. Immun. 68:5293-5298.

Darville, T, Andrews, C.W., Jr., Rank, R.G. 2000. Does inhibition of tumor necrosis factor-alpha affect chlamydial genital tract infection in mice and guinea pigs? Infect. Immun. 68:5299-5305.

Rank, R.G. 1999. Models of Immunity. Stephens, R.S. (ed). In Chlamydia : Biology, Pathogenesis, and Immunity , American Society for Microbiology, Washington , D.C. pp. 239-296.

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