SCIENTIFIC DISCOVERIES

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.

AIDS Pathogenesis

• 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.

AIDS Vaccines

• Developed mucosal vaccine approaches.
• Successfully tested new AIDS vaccine based on live vesticular stomatitis virus (VSV)-vectors.

Tuberculosis

• 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.

Malaria

• 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).

Microsporidiosis

• 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.

Gene Therapy

• 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.