Ouachita Baptist University | 1982 | B.S.
Vice President and Chief Academic Officer
Downers Grove, IL
Chicago College of Osteopathic Medicine
College of Dental Medicine-Illinois
College of Veterinary Medicine
Biomedical Sciences (M.A.)
Biomedical Sciences (M.B.S.)
Ouachita Baptist University | 1982 | B.S.
Infectious diseases, immunology, immunopathological basis of disease caused by pathogens of the genus: Chlamydia
Chlamydial infections are ubiquitous in humans and animals. In the U.S. and other industrialized societies, selected strains of Chlamydia trachomatis cause sexually transmitted infections that lead to pelvic inflammatory disease, tubal factor infertility and ectopic pregnancy. In the less-developed world a different set of C. trachomatis strains cause the most common form of infectious blindness, trachoma, from which the species derives its name. In these areas, rather than sexual transmission, key environmental factors are involved in transmission. C. pneumoniae is a common respiratory infection in humans and has also been linked to several chronic disease states. C. psittaci infections cause ocular, respiratory, urogenital and gastrointestinal disease in domestic animals and wildlife and may cross the species barrier and cause infection in humans.
My laboratory is dedicated to discovering how chlamydial agents induce inflammatory damage in humans and animals and how best protective immunity can be accomplished so that we may someday derive a safe and efficacious vaccine. Most of our work is accomplished through the lens of a mouse model. However, our long-term plans include extension of our findings for application in companion and food animals, wildlife and eventually humans. We actively pursue partnerships in this regard and currently have collaborations in the U.S., U.K., Australia and India.
SELECTED RESEARCH PROJECTS
Project I: The role of the chlamydial plasmid in pathogenesis and immunity in a mouse model. Both C. trachomatis and C. muridarum are known to routinely carry a plasmid. For many years, the role of this plasmid in establishing infection, eliciting immunity and/or causing disease was unknown. It has more recently been shown that the plasmid moderates infectivity and phenotype in vitro (cell culture) and virulence in vivo - in the mouse (and presumably in human infections). We seek to understand how the plasmid effects virulence, affects chromosomal gene expression, and elicits immunological protection. Our current collaborations on this project include the laboratories of Professor Ian N. Clarke http://www.southampton.ac.uk/medicine/about/staff/inc.page#background(the University of Southampton School of Medicine, Southampton, U.K.) and Dr. Ashlesh K. Murthy https://www.midwestern.edu/ashleshmurthy.html (Midwestern University, U.S.A.).
Project II: Using chlamydial genomic variants to understand chlamydial immunity and pathogenesis. We have shown that, like all bacteria, the genome of chlamydia exhibits spontaneous mutation as a natural process. We have more recently shown that many genomic variants exist within two commonly used strains of C. muridarum. These variations are in the form of small or single nucleotide polymorphisms (1, 2 or 3 base pair additions, substitutions or deletions). We believe that some of these mutations may lead to attenuation of virulence while in culture thereby weakening the pathogen when introduced into the mouse host. In this Project, our aim is to cross-map the chlamydial genes responsible for virulence with the host genes associated with resistance and susceptibility. When accomplished, we believe that we will be able to identify critical host and pathogen genes. The interface of these genes will point us to a greater understanding of why some people develop chronic disease states following chlamydial infection and others develop a protective immune response. The results will have a direct impact on development of an efficacious chlamydial vaccine. Our collaborators on this project include Drs. Jan Peters and Gerry Byrne (University of Tennessee Health Sciences Center) and the Regional Biocontainment Laboratory in Memphis, Tennessee.
Project III: Inflammation and pathogenesis in chlamydial infection. In this project we explore the molecular mechanisms that induce inflammatory damage during chlamydial infections. Many labs throughout the world are currently studying inflammatory mechanisms and "signaling cascades" in chlamydial infection. These effectors and effector pathways (e.g. cytokines and chemokines) are important in understanding the "come hither" mechanisms that elicit inflammatory damage during and immediately following a chlamydial infection. Rather further study studying signaling, our lab has focused on the mechanisms, downstream of the signaling, that actually affect tissue damage. We have shown, for example, that innate mechanisms such as oxygen free radicals and matrix metalloproteinases contribute significantly to the damage that occurs during chlamydial infection and further postulate that other mechanisms are also at play. We now work with the Murthy Lab https://www.midwestern.edu/ashleshmurthy.html at Midwestern University to understand the adaptive immune mechanisms mediated by CD8+ T lymphocytes later in infection and how innate and adaptive mechanism are elicited together to result in chlamydia infection-associated immunopathology. Understanding how the damage occurs will help us to derive a vaccine that is both safe and efficacious.
The mouse as a model for the study of human pelvic inflammatory disease of chlamydial etiology (Project III). Panel A and B: Oviduct (arrows), uterus ("U") and ovary ("O") of an uninfected mouse (Panel A) or a mouse at 14 days post-infection with Chlamydia muridarum (Panel B). Panel C and D: Hematoxylin and eosin stained histological sections of the oviduct shown in Panels A and B. The lumen (L) of the oviduct from the uninfected mouse (Panels A and C) is patent and plicae are intact. The oviduct from the infected mouse is inflamed with acute and chronic inflammatory cells occluding the lumen (L) and plicae are destroyed (Panel D). The image on the far right is a frozen cross section of an inflamed oviduct stained using fluorescence immunohistochemistry for matrix metalloproteinase-9 (MMP-9). MMP-9 is stained red/pink and cell nuclei are stained blue. The section depicts the accumulation of acute inflammatory cells elaborating MMP-9 (arrows) at the basolateral surface of the epithelium (E) and some inflammatory cells are undergoing transepithelial migration into the lumen. The cells seem to discharge MMP-9 as they migrate across the infected epithelial layer and linto the lumen of the oviduct becasue the cells in the lumen have reduced MMP-9 staining. We believe MMP-9 is responsible for a siginficant portion of the tissue destruction that occurs during infection in this model.
Gallegos KM, Taylor CR, Rabulinski DJ, Del Toro R, Girgis DE, Jourha D, Tiwari V, Desai UR, Ramsey KH. A Synthetic, Small, Sulfated Agent Is a Promising Inhibitor of Chlamydia spp. Infection in vivo. Front Microbiol. 2019 Jan 16;9:3269. doi: 10.3389/fmicb.2018.03269. eCollection 2018. PubMed PMID:30700982; PubMed Central PMCID: PMC6343517. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343517/
Zafiratos MT, Cottrell JT, Manam S, Henderson KK, Ramsey KH, Murthy AK. Tumor necrosis factor receptor superfamily members 1a and 1b contribute to exacerbation of atherosclerosis by Chlamydia pneumoniae in mice. Microbes Infect. 2019 Mar;21(2):104-108. doi: 10.1016/j.micinf.2018.09.003. Epub 2018 Oct 4. PubMed PMID: 30292879; PubMed Central PMCID: PMC6445723.
Li W, Gudipaty P, Li C, Henderson KK, Ramsey KH, Murthy AK. Intranasal immunization with recombinant chlamydial protease-like activity factor attenuates atherosclerotic pathology following Chlamydia pneumoniae infection in mice. Immunol Cell Biol. 2019 Jan;97(1):85-91. doi: 10.1111/imcb.12192. Epub 2018 Aug 23. PubMed PMID: 30051926; PubMed Central PMCID: PMC6338504. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6338504/
Skilton RJ, Wang Y, O'Neill C, Filardo S, Marsh P, Bénard A, Thomson NR, Ramsey KH, Clarke IN. The Chlamydia muridarum plasmid revisited: new insights into growth kinetics. Wellcome Open Res. 2018 Mar 8;3:25. doi:10.12688/wellcomeopenres.13905.1. eCollection 2018. PubMed PMID: 29657985; PubMed Central PMCID: PMC5871946. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5871946/
Sigar IM, Schripsema JH, Kelly KA, Murthy AK, Manam S, Ramsey KH. Elimination of Mycoplasma contamination in Chlamydia stocks as a result of in vivo passage or plaque isolation. BMC Res Notes. 2018 Jun 7;11(1):361. doi:10.1186/s13104-018-3455-x. PubMed PMID: 29880030; PubMed Central PMCID:PMC5992720. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5992720/
Winstanley CE, Ramsey KH, Marsh P, Clarke IN. Development of an enzyme-linked immunosorbent assay for the detection of antibodies to a common urogenital derivative of Chlamydia trachomatis plasmid-encoded PGP3 . J Immunol Methods. 2017 Jun;445:23-30. doi: 10.1016/j.jim.2017.03.002. Epub 2017 Mar 7. PMID: 28283408
Murthy AK, Li W, Ramsey KH. Immunopathogenesis of Chlamydial infections. Curr Top Microbiol Immunol. 2016 Jul 2. [Epub ahead of print] PMID: 27370346 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6086136/
Ramsey KH, Sigar IM, Schripsema JH, Townsend KE, Barry RJ, Peters J, Platt KB. Detection of Chlamydia infection in Peromyscus species rodents from sylvatic and laboratory sources. Pathog Dis. 2016 Apr;74(3). pii: ftv129. doi: 10.1093/femspd/ftv129. Epub 2016 Jan 4. PMID: 26733499. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6929162/
Vlcek KR, Li W, Manam S, Zanotti B, Nicholson BJ, Ramsey KH, Murthy AK. The contribution of Chlamydia-specific CD8+ T cells to upper genital tract pathology. Immunol Cell Biol. 2016 Feb;94(2):208-12. doi: 10.1038/icb.2015.74. Epub 2015 Sep 1. PMID: 26323581. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4747851/
Zafiratos, MT, Manam, S, Henderson, KK, Ramsey, KH, Murthy, AK. CD8+ T cells mediate Chlamydia pneumoniae-induced atherosclerosis in mice. Pathog Dis. 2015 Oct;73(7). pii: ftv052. doi: 10.1093/femspd/ftv052. Epub 2015 Jul 27. PMID: 26220574. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4830221/
Jasper DK, Sigar IM, Schripsema JH, Sainvil CK, Smith CL, Yeruva L, Rank RG,Murthy AK, Widder JR, Ramsey KH. Genomic variant representation in a Chlamydia population is dynamic and adaptive with dependence on in vitro and in vivo passage. Pathog Dis. 2015 Feb;73(1):1-12. doi: 10.1093/femspd/ftv003. Epub 2015 Jan 28. PubMed PMID: 25673672. http://femspd.oxfordjournals.org/content/73/1/1.14.long
Manam S, Thomas JD, Li W, Maladore A, Schripsema JH, Ramsey KH, Murthy AK. Tumor Necrosis Factor (TNF) Receptor Superfamily Member 1b on CD8+ T Cells and TNF Receptor Superfamily Member 1a on Non-CD8+ T Cells Contribute Significantly to Upper Genital Tract Pathology Following Chlamydial Infection. J Infect Dis. 2014 Dec 30. pii: jiu839. [Epub ahead of print] PubMed PMID: 25552370. http://jid.oxfordjournals.org/content/early/2015/01/27/infdis.jiu839.long
Ramsey, KH, Schripsema JH, Smith BJ, Wang Y, Jham BC, O'Hagan KP, Thomson NR, Murthy AK, Skilton RJ, Chu P, Clarke IN. Plasmid CDS5 influences infectivity and virulence in a mouse model of Chlamydia trachomatis urogenital infection. Infect Immun. 2014 Aug;82(8):3341-9. doi: 10.1128/IAI.01795-14. Epub 2014 May 27. PubMed PMID: 24866804; PubMed Central PMCID: PMC4136204. http://iai.asm.org/content/82/8/3341.long
Wang Y, Cutcliffe LT, Skilton RJ, Ramsey KH, Thomson NR, Clarke IN. The genetic basis of plasmid tropism between Chlamydia trachomatis and Chlamydia muridarum. Pathog Dis. 2014 Oct;72(1):19-23. doi: 10.1111/2049-632X.12175. Epub 2014 May 8. PubMed PMID: 24700815; PubMed Central PMCID: PMC4314687. http://femspd.oxfordjournals.org/content/72/1/19.long
Andrew DW, Cochrane M, Schripsema JH, Ramsey KH, Dando SJ, O'Meara CP, Timms P, Beagley KW. The duration of Chlamydia muridarum genital tract infection and associated chronic pathological changes are reduced in IL-17 knockout mice but protection is not increased further by immunization. PLoS One. 2013 Sep 20;8(9):e76664. doi: 10.1371/journal.pone.0076664. eCollection 2013. PubMed PMID: 24073293; PubMed Central PMCID: PMC3779189. http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0076664
Sigar IM, Schripsema JH, Wang Y, Clarke IN, Cutcliffe LT, Seth-Smith, HM, Thomson NR, Bjartling C, Unemo M, Persson K, Ramsey KH. Plasmid deficiency in urogenital isolates of Chlamydia trachomatis reduces infectivity and virulence in a mouse model. Pathog Dis. 2014 Feb;70(1):61-9. doi: 10.1111/2049-632X.12086. Epub 2013 Sep 10. PubMed PMID: 24022847; PubMed Central PMCID: PMC4300952. http://femspd.oxfordjournals.org/content/70/1/61.long
Tiwari V, Maus E, Sigar IM, Ramsey KH, Shukla D. Role of heparan sulfate in sexually transmitted infections. Glycobiology. 2012 Nov;22(11):1402-12. doi: 10.1093/glycob/cws106. Epub 2012 Jul 6. Review. PubMed PMID: 22773448; PubMed Central PMCID: PMC3481906. http://glycob.oxfordjournals.org/content/22/11/1402.long
American Society for Microbiology (former)
Society for Mucosal Immunology (former)
Society for Armed Forces Medical Laboratory Sciences (former)
Association of Military Surgeons of the U.S. (former)
Reserve Officer Association (former)
International Assoc. of Medical Science Educators
Chlamydia Basic Research Society (Charter and Founding Member)
Assoc. of Medical School Microbiology and Immunology Chairs (former)
Tri-Beta Biological Honor Society (at Ouachita Bapt. Univ)
OBU Distinguished Student-Athlete – Varsity Football (at Ouachita Bapt. Univ)
OBU Distinguished Military Graduate - Army ROTC (at Ouachita Bapt. Univ)
Who's Who Among American Colleges and Universities (at Univ. Ark. Med. Sciences)
Microbiology Teacher of the Year (Midwestern University)
Littlejohn Award for Teaching, Research, and Service (Midwestern University)
Irvin R. Korr Research Award (AOA Foundation)
Meritorious Service Medal
Army Commendation Medal (With 3 Oak Leaf Clusters)
The Army Achievement Medal (With 1 Oak Leaf Cluster)
Army Superior Unit Award
National Defense Service Medal
Southwest Asia Service Medal (With 2 Bronze Service Stars)
Army Service Ribbon
Army Reserve Components Achievement Medal
Kuwait Liberation Medal
Defense of Saudi Arabia Medal
Meritorious Service Meda