Robert Belland, Ph.D.


Robert Belland,  Ph.D.,

Associate Professor
858 Madison Ave.
Room 801
Memphis, TN 38163
Email: rbelland@uthsc.edu
Phone: 901-448-8544
Fax: 901-448-7360

Research Interests

My research effort is directed at understanding the pathogenic characteristics of Chlamydia trachomatis and C. pneumoniae that contribute to chronic human diseases such as trachoma, infertility, reactive arthritis and atherosclerosis. These disease syndromes generally follow less severe acute infections. The development of long-term, persistent disease states is complex and it is not clear whether disease progression is due to specific characteristics of the host or pathogen. We have used a functional genomic approach to identify pathogen-specific genotypes and phenotypes associated with chronic diseases. In the future we would like to complement these studies by determining host-susceptibility patterns associated with chronic disease.

Chlamydia pneumoniae and Atherosclerosis

Exposure to C. pneumoniae is extremely common and respiratory infections occur repeatedly among most people. Strong associations exist between C. pneumoniae infection and atherosclerosis as demonstrated by (a) sero-epidemiological studies showing patients with cardiovascular disease have higher titers of anti-C. pneumoniae antibodies compared with control patients, (b) detection of the organism within atherosclerotic lesions, but not adjacent normal tissue by immunohistochemistry, PCR and electron microscopy and by culturing the organism from lesions (c) demonstrating that C. pneumoniae can either initiate lesion development or cause exacerbation of lesions in rabbit and mouse animal models, respectively. The association of this organism with atherosclerosis also has provided sufficient impetus to conduct a variety of human secondary prevention antibiotic treatment trials. Results of these studies have been mixed, and thus far no clear long lasting benefit has emerged from these types of investigations. Studies of C. pneumoniae pathogenesis have shown that the organism can infect many cell types associated with both respiratory and cardiovascular sites including lung epithelium and resident alveolar macrophages, circulating monocytes, arterial smooth muscle cells and vascular endothelium. Infected cells have been shown to exhibit characteristics associated with the development of cardiovascular disease (e.g. secretion of proinflammatory cytokines and procoagulants by infected endothelial cells and foam cell formation by infected macrophages). More detailed analysis of C. pneumoniae pathogenesis has been aided by the availability of genomic sequence information. Genomic and proteomic analyses of C. pneumonie infections in relevant cell types will help define the pathogenic potential of the organism in both respiratory and cardiovascular disease. C. pneumoniae, like all chlamydiae, is an obligate intracellular prokaryotic pathogen. Unlike C. trachomatis, the other major human chlamydial pathogen, which exhibits an in vivo tropism for mucosal epithelial cells, C. pneumoniae can infect and survive in a wider array of host cell types, including lung epithelium, resident macrophages (alveolar and monocyte derived), circulating monocytes, arterial smooth muscle cells and vascular endothelium. C. pneumoniae can infect and modify the physiology of the various cell types present in the lung, circulation, and atheroma itself and may transit from the lung to the atheroma via circulating and. The C. pneumoniae intracellular developmental cycle resembles that of other chlamydiae in its general features (Fig.1). research_pic_1

Chlamydiae remain within the confines of the host cell vesicle throughout their cycle of intracellular development but modify this structure in several ways during their growth phase. The final stages of chlamydial growth during a productive infection involve differentiation of RB back to EB. This is accompanied by lysis of the host cell or direct release of EB. Productive infections are only one of several possible outcomes of chlamydial interactions within any given host cell. Chronic chlamydial infections have been recognized in vivo for decades and physiologic mediators of persistence include immune-regulated cytokines such as gamma-interferon (IFN-g) and tumor necrosis factor alpha (TNF-a). These attributes are consistent with involvement of chronic diseases such as atherosclerosis.
C. pneumoniae has the capacity to initiate and propagate inflammation in ways that contribute to atherosclerosis. The pathogen likely accesses the vasculature during local inflammation in a lower respiratory tract infection. The organism disseminates systemically but exhibits tropism to arterial vasculature. The pathogen can infect and multiply within all cell types commonly found in the atheroma, including coronary artery endothelial cells, macrophages, and aortic artery smooth muscle cells.
research_pic_2

One growth characteristic likely to be associated with long-term disease in cardiovascular tissue is the tendency or ability of the isolate to establish persistent infections. The application of genomic analyses to clinical isolates should provide useful information in the development of therapeutic approaches that target isolates most likely to be associated with CVD and should help in the development of diagnostic tools that indicate the presence of isolates associated with the development of CVD.

Figure Legends

Figure 1. The developmental cycle of C. pneumoniae. The normal cycle may be disrupted by the induction of persistence due to nutritional deprivation, antibiotic treatment, or growth in specific cell types and the appearance of large aberrant bacterial forms. Reactivation of the normal developmental cycle can be seen in many cases when the inducer of persistence is removed.

Figure 2. The polyclonal nature of C. pneumoniae strains causing respiratory disease can be demonstrated by the presence of distinct mixtures of bacterial genotypes (as described in Table 1) in strain isolates. Certain genotypes may exhibit a selective advantage in the ability to disseminate or establish infection in cardiovascular sites.

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Education

  • B.Sc., 1981, University of Victoria (Biochemistry and Microbiology), Victoria, British Columbia, Canada
  • Ph.D., 1987, University of Victoria (Biochemistry), Victoria, British Columbia, Canada

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