Scientific Discoveries

AIDS Pathogenesis

• Demonstrated the intestinal immune system is the primary target of SIV infection which was later validated in humans.
• Defined the early time course and key target cells of SIV infection, which was also validated in HIV-infected humans.
• Developed the macaque model of neurologic AIDS.
• Demonstrated that neuroinvasion by SIV occurs within days of infection and involves specific leukocyte and endothelial adhesion molecules and chemokines.
• Described the early targets and effects of SIV infection on immune cells and responses in the gut, spleen, bone marrow, brain, liver, and thymus in vivo.
• Developed infection models using novel mutant viruses to better understand the viral reservoir and antiviral immune responses.

AIDS Vaccines

• Developed novel mucosal vaccine protocols and approaches.
• Tested new vaccine candidates and adjuvants in infant and adult macaques

Heterosexual Transmission of AIDS

• Developed the macaque model of heterosexual transmission of SIV.
• Defined hormonal influences on vaginal transmission of SIV, and first demonstrated progesterone increases SIV/HIV vaginal transmission rates.
• Demonstrated the protective effects of topical vaginal microbicides to prevent heterosexual transmission of AIDS.
• Identified the first cellular and molecular targets involved in both vaginal and rectal SIV/SHIV transmission.

Origins of AIDS

• Proved that SIV was an ancient virus much older than originally believed.
• Identified the sooty mangabey as the natural host of SIV and the most likely source of Human Immunodeficiency Virus-2 (HIV-2).
• Identified a novel SIV in red-capped and mandrills.

• Demonstrated that submissive behavior displayed upon the initial introduction into pair housing results in a lower level of delayed incompatibility
• Developed a minimally invasive thoracoscopic surgical procedure to acquire biopsies of the thymus, dramatically decreasing surgical morbidity
• Confirmed the efficacy of a commercially available transdermal anthelmintic agent, reducing the need for injections. 
• Implemented the use of videoendopic biopsy procedures in nonhuman primate intestines, to replace full thickness intestinal resection and anastomosis for biopsy procedures.
• Established that the social housing of nonhuman primates improved their ability to adapt to stressors in their environment. 
• Performed chorionic villous sampling in pregnant rhesus macaques to collect biopsies for genetic testing.
• Developed a chorionic catheterization model for the thoracic duct to collect cells for studies in AIDS immunity. 
• Demonstrated the feasibility and positive effects of social housing of adult male rhesus monkeys. 
• Demonstrated that clinical observations captured on video compared to direct observation by humans provide information important to developing an accurate clinical diagnosis in rhesus monkeys. 
• Demonstrated that an effective multiple-drug antibiotic therapy used to treat idiopathic enterocolitis in rhesus monkeys only transiently and insignificantly alters the intestinal microbiome.
• Demonstrated positive effects of pharmacological methods for improving the outcome of pair introductions and breeding group formation

• 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.

• Developed an array of biodefense-relevant nonhuman primate disease models including the pathogenic alphaviruses and poxviruses. 
• Demonstrated the first therapeutic treatment and rescue of nonhuman primates from a lethal aerosol of ricin toxin. 
• Demonstrated the utility and correlative association of physiological response as an endpoint in vaccine evaluation utilizing nonhuman primate model of Eastern Equine Encephalitis infection. 
• Established a nonhuman primate model of inhalation glanders (Burkholderia mallei) and demonstrated utility in a candidate vaccine trial. 
• Established the immunogenicity and protective efficacy of a ricin vaccine in a nonhuman primate model of aerosolized ricin toxin. 

• Developed the first experimental nonhuman primate model of primary congenital CMV infection in rhesus macaques for studies on immune protection and CMV vaccine development
• First demonstration of placental rhesus CMV transmission in pregnant macaques
• Demonstrated that maternal CD4+ T lymphocytes are critical for preventing placental CMV transmission and protecting against fetal loss
• Showed that delayed onset of anti-CMV neutralizing antibodies and CMV-specific T cell immunity increased risk of congenital CMV transmission
• Demonstrated that passively infused pre-existing high titer anti-CMV antibodies are sufficient for protection against congenital CMV infection
• Showed evidence of immune selection pressure on transmitted viral variants

• Helped establish the rhesus macaque and African green monkey as successful models of SARS CoV2 transmission and infection, as well as models of COVID and long COVID pathogenesis
• Demonstrated the persistence of SARS CoV2 in aersosol suspension
• Demonstrated the neuropathology of SARS CoV2 infection in nonhuman primates 
• Developed a novel NHP model for COVID-19 using pigtail macaques and determined the impact of HIV/SIV infection on COVID disease in this model
• Developed novel assays for measuring viral replication and neutralization
• Used viral genomic sequencing to measure viral evolution in NHP and human samples
• Tested novel vaccines and adjuvants
• Tested the impacts of monoclonal antibodies and convalescent serum on COVID disease 
• Helped to develop novel diagnostic approaches

• Isolated and characterized a new rotavirus from juvenile monkeys (TUCH)
• TUCH classified as simian rotavirus, genotype G1P[8].
• Identified rotavirus VP6-specific CD4+ T cell epitopes.
• Reported role of rotavirus VP4 in biliary atresia and cholangiopathy.
• Reported rotavirus interspecies transmission and reassortment.
• Isolated and characterized a new enteric calicivirus of rhesus origin (TV):
• New genus within family Caliciviridae, i.e., Recovirus.
• Recovered infectious TV from transfected cells in vitro.
• Established juvenile rhesus macaque model of TV infection.
• Demonstrated presence of TV antibodies in humans.
• Described genetic diversity and human HBGA-TV interactions.

Established a nonhuman primate model of rotavirus infection

• Isolated and characterized a new rotavirus of simian origina 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 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 entrocolitis in rhesus macaques and its similarieis to Inflammatory Bowel Disease of humans. 

Lyme Disease Diagnosis and Treatment

• Developed a peptide-based diagnostic immunoassay (C6) 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 the antigen-dependent dynamics of longitudinal antibody responses to B. burgdorferi infection in monkeys; used these findings to select a combination of antigens for diagnostic test development.
• Developed a Luminex®-based multi-antigen diagnostic test for serodiagnosis of Lyme disease. This test expands the specificity of detection across early and late phases of disease.
• Discovered that current antibiotic monotherapy does not clear B. burgdorferi from infected primates. Further study revealed that the persistent spirochetes are living and induce mild to moderate inflammation in multiple organs, including the heart, joints and peripheral nervous system.
• Identified persistent Borrelia in the brain and spinal cord of a treated Lyme disease patient who developed Lewy body dementia.

Lyme Disease Pathogenesis and Spirochete Biology

• Established the rhesus monkey model of Lyme disease.
• Discovered that neuronal degeneration secondary to inflammation could cause the mononeuropathy multiplex commonly observed in neuroborreliosis of the peripheral nervous system.
• Discovered that inflammation is the key effector of Lyme disease in the central nervous system.
• Discovered an immune evasion mechanism that Borrelia burgdorferi, the spirochete that causes the disease, may use to cause persistent infections.
• 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.
• 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 Fibroblast growth factor receptors and fibroblast growth factors as novel mediators of inflammation in brain glial cells due to B. burgdorferi exposure.

• 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.
• Applied genotyping diagnostics to identify animal reservoirs of microsporidia species that pose a risk for transmission to humans.
• Contributed to genome sequencing and transcriptome projects for several microsporidia species that infect humans, nonhuman primates (and other animals). 
• Defined mechanisms of macrophage-mediated destruction of intracellular microsporidia species that infect humans and nonhuman primates.

• Characterized and applied as therapies mesenchymal stem cells from bone marrow and adipose tissue of rhesus macaques.
• Developed and tested novel CAR-T cell strategies targeting SIV.
• Started a tissue engineering research program focused on the nonhuman primate model.
• Successfully developed a tissue engineered nipple areolar complex in the NHP model.
• Developing novel neurotropic adeno-associated virus vectors via virus evolution for gene therapy applications.
• Developed novel gene therapy vectors targeting both the brain and hematopoietic stem cells for the treatment of Krabbe’s disease.

• Developed a monkey model of RSV infection.
• Successfully tested multiple RSV vaccines.
• Successfully tested monoclonal antibody treatment against RSV F glycoprotein, that was later FDA approved. 

• Developed a monkey model of varicella (chickenpox) and zoster (shingles.)
• Successfully tested the first antiviral treatment Acyclovir, which was later FDA-approved. 

• Established various model of TB in rhesus monkeys to study active TB, chemotherapy and response to vaccination, as well as to study TB latency, reactivation by various factors including SIV co-infection, and the impact of ART and LTBI chemotherapy.
• Developed a new experimental vaccine which shows exceptional promise as a novel anti-TB vaccine vehicle.
• Established various model of TB in rhesus monkeys to study active TB, chemotherapy and response to vaccination, as well as to study TB latency, reactivation by various factors including SIV co-infection, and the impact of ART and LTBI chemotherapy.
• Developed a new research area in the field of host-directed therapies against TB, including testing anti-cancer compound Imatinib, which is now included in an NIH-funded clinical trial in South Africa.
• Developed a new approach to testing the effectiveness of LTBI chemotherapy in the macaque model.
• Identified a major role for hypoxia response program of M. tuberculosis in persistence in lung granulomas.
• Identified a major role for B cells in protection from TB.

•    Zika virus infection of pregnant animals and pathology in infants. 
•    Discovered that Zika virus infection during early pregnancy results in frequent fetal loss. 
•    Found that ZIKV causes central nervous system pathogenesis in adults