The Tulane National Primate Research Center has been involved in a variety of important multidisciplinary projects focusing on areas of biomedical research with high priority concerns for human health. The information below highlights some of these scientific discoveries.
Origins of AIDS
- Identified the sooty mangabey as the natural host of Simian Immunodeficiency Virus (SIV) and the most likely source of Human Immunodeficiency Virus-2 (HIV-2).
- Identified a novel SIV in red-capped mangabeys and mandrills.
- Found evidence of infection in persons with SIV from mandrills in Cameroon and Gabon.
- Discovered and characterized HIV-1 group N.
- Established a link between SIVmac emergence and kuru experiments carried out in the 1970s and identified the origins of SIVmac.
- Demonstrated that the intestinal immune system is the primary target of SIV infection.
- Defined the early time course of SIV infection.
- Developed the macaque model of neurologicAIDS.
- Defined the cell types infected.
- Demonstrated that neuroinvasion by SIV occurs within days of infection and involves leukocyte and endothelial adhesion molecules and chemokines.
- Described the early targets and effects of SIV infection on the thymus in vivo.
Heterosexual Transmission of AIDS
- Developed the macaque model of heterosexual transmission of SIV.
- Defined hormonal influences on vaginal transmission of SIV.
- Developed microbicides to prevent heterosexual transmission of AIDS and demonstrated the effectiveness of the approach to prevent vaginal transmission of SIV in macaques.
- Developed mucosal vaccine approaches.
- Successfully tested new AIDS vaccine based on live vesticular stomatitis virus (VSV)-vectors.
- Established a chronic model of tuberculosis in rhesus monkeys.
- Defined TB strain differences, dosage requirements and pathology of the chronic model.
- Established that the chronic model can be used in animals co-infected with SIV.
Lyme Disease Pathogenesis
- Established the rhesus monkey model of Lyme disease.
- Discovered an immune evasion mechanism that Borrelia burgdorferi, the spirochete that causes the disease, may use to cause persistent infections.
- Discovered that B cells produce the regulatory cytokine IFN-gamma in animals infected with B. burdoferi.
- Discovered that spirochetes elicit not only inflammatory but also anti-inflammatory cytokines from monocytes, thus contributing a method to control the inflammation they themselves cause.
Pathogenesis of Lyme Neuroborreliosis
- Discovered that neuronal degeneration secondary to inflammation could cause the mononeuropathy multiplex commonly observed in neuroborreliosis of the peripheral nervous system.
- Discovered that astrogliosis may be a major mechanism leading to neurologic symptoms of Lyme disease in the central nervous system.
Lyme Disease Diagnosis and Spirochetal Biology
- Developed a peptide-based diagnostic immunoenzyme assay that outperforms the currently available two-tier test. This assay is now approved by the Food and Drug Administration (FDA) for use in humans and by the USDA for use in animals.
- Discovered that B. burgdorferi regulates gene expression in a cell-density dependent manner.
- Discovered that B. burgdorferi antigenic variation does not occur in the tick.
- Discovered the parasite stage responsible for malaria relapse (the hypnozoite).
- Developed molecular markers for malaria relapse.
- Developed the first monkey model of malaria during pregnancy.
- Developed the only successful model of congenital malaria.
- Established that placental malaria in the macaque is similar to human placental malaria.
- Ultrasonographic exams established intrauterine growth retardation (IUGR) and not prematurity as the cause of low birth weight (potential model of IUGR).
- Identified for the first time a prokaryotic gene in a eukaryotic organism, the microsporidian Vittaforma corneae. This led to the inclusion of fluoroquinolones as lead compounds for treating microsporidiosis.
- Isolated and identified a new microsporidian species, Encephalitozoon hellem, which infects humans and birds.
- Identified unique genotype markers among isolates of Encephalitozoon cuniculi.
- Developed improved Polymerase Chain Reaction (PCR)-based methods for diagnosing microsporidiosis.
- Developed in vitro and in vivo models for testing and identifying drugs with antimicrosporidial activity.
- Isolated and partially characterized mesenchymal stem cells from bone marrow and adipose tissue of rhesus macaques.
- Proved that in utero inoculation of recombinant Adeno-Associated Virus (AAV) resulted in transduction of pericapillary astrocytes and occasional neurons.
- Demonstrated that the administration of perfluorochemical liquids improved in vivo gene transfer to the lung, with a focus on treatment of cystic fibrosis.
- Showed that rhesus dendritic cells can be made to stably express gene products with lentivirus vectors and migrate to the lymph nodes upon introduction into animals.
- Successfully isolated adult nonhuman primate mesenchymal stem cells from bone marrow and adipose tissue.
- Successfully demonstrated that macaque mesenchymal stem cells can differentiate into neural cells.
Assisted Reproductive Technology
- Developed a system for the in vitro production of rhesus embryos.
- Superovulation and retrieval of mature rhesus oocytes.
- Developed rhesus embryos to the blastocyst stage following in vitro fertilization and culture.
- Cryopreserved in vitro-derived rhesus embryos.
- Successfully transferred fresh and cryopreserved normal rhesus embryos resulting in five single and two sets of twin pregnancies.
Models of Gastrointestinal Disease
- Established a nonhuman primate model of rotavirus infection.
- Isolated and characterized a new rotavirus of simian origin that was classified as genotype P.
- Developed new molecular tool (real-time PCR) for quantitative evaluation of rotavirus infection.
- Chronic enterocolitis of rhesus macaques
- Described new cytolethal distending toxin-producing strain of Campylobacter jejuni isolated from nonhuman primates.
- Determined inflammatory cytokine genes that are upregulated during chronic enterocolitis.
- Visualized in situ cytokine-producing macrophage and T cell subsets that are involved in chronic enterocolitis.
- Demonstrated polymicrobial origins of chronic enterocolitis in rhesus macaques and its similarities to Inflammatory Bowel Disease of humans.