Treponema pallidum pertenue, an endemic treponemal disease, also known as yaws, is considered a neglected tropical disease by the World Health Organization (WHO). Approximately 65,000 new cases of yaws occur each year in thirteen endemic countries, with almost 85% of all infections occurring in Ghana, Papua New Guinea, and the Solomon Islands. The disease is predominantly seen in children, transmitted by direct contact with the skin. Wild nonhuman primates (NHP) in Africa have been shown to be infected with T. pallidum pertenue. These African NHP cases of infection add to the speculation that free-ranging NHP may serve as a mammalian reservoir of the pathogen. Interestingly, human and NHP cases of T. pallidum pertenue in Africa often occur in areas where the groups are sympatric. In Asia, the human-NHP interface is generally more widespread and diverse, characterized by pet primates, temple monkeys, and wild and urban primates. Yaws infections in humans continues to be pervasive in many of the areas where humans and NHP interact. The goal of our project’s screening efforts is to further characterize whether these Asian monkey populations are infected with T. pallidum pertenue. Using standard serological assays to detect treponemal antibodies, we have screened approximately 800 NHP serum samples from eight countries representing six contexts and ten species. Our preliminary results indicate that T. pallidum pertenue can be detected in discreet NHP populations particularly where there is enhanced interaction between the human and NHP populations, and the disease is still largely endemic in the human population. In order for a disease to become eradicable, it is imperative that there be no mammalian reservoir. As the WHO seeks to eradicate the disease via a second global campaign, this research will be able to tell us whether treponemal infections are present in NHP populations.

While HIV-related immunosuppression is a well-studied risk factor of tuberculosis (TB) infection and reactivation, other forms of immune system modulation have yet to be explored in great depth. Mycobacterium tuberculosis complex (MTBC) infects one third of the global population, with 5-10% developing active TB. Understanding risk factors of a high burden infectious disease such as TB is critical to improving control and prevention in humans. This study uses a population of biomedical macaques to explore the relationship between pregnancy history and TB susceptibility. A correlation between the factors would flag pregnant women as a unique high-risk population. It is anticipated that the number of pregnancies will be predictive of increased TB susceptibility, with individuals who have had multiple pregnancies more likely to be infected with MTBC. Individuals without a history of pregnancy are expected to have similar rates of infection as males in our study. Nonhuman primate(s) (NHP) are used as models of human infectious diseases and are also susceptible to infection with MTBC. The Oral Swab PCR (OSP) uses a buccal swab to sample saliva and cells from the interior of a subject’s mouth. This protocol has been previously validated for the detection of MTBC in NHP and humans. We used an extensive archive of buccal swabs collected from biomedical macaques to screen for MTBC. Following OSP screening for MTBC, statistical tests were run to test for A) sex-specific differences in infection and B) the impact of number and frequency of pregnancies on infection within females. An association between pregnancy and TB supports existing research and furthers the question on how pregnancy relates to the reactivation of latent TB. Currently, mechanisms for reactivation of latent TB are poorly understood making it difficult to predict how, or why TB reactivation occurs. Further research is needed to examine immunosuppression and reactivation.

Congenital heart disease is a problem with the structure of the heart that is present at birth. In the United States, about 40,000 babies are affected by this disease annually. In our lab, zebrafish are used to investigate the genetic causes of this disease. Previous research investigations from our lab have shown that two important genes that are responsible for the regulation of heart muscle are Pbx4 and Pbx2, which are homeodomain transcription factors. Pbx2 and Pbx4 are genes of interest because their roles in heart development are not completely understood. CRISPR/Cas9 method is a method that can be used to target specific DNA sequences and create modifications in the genome. We used this method to engineer different strains of zebrafish with a variety of Pbx gene alleles to determine the role of the Pbx factors in heart development. In order to figure out how the different alleles affect the Pbx genes, each of the strains were observed for phenotype. The null alleles of Pbx2 and Pbx4 were used to demonstrate that embryos lacking both of these factors have severe defects in heart muscle differentiation and outflow tract formation. Then, in-frame deletions were made in the Pbx4 gene demonstrating the importance of an alanine tract for critical functions in heart development. Next, a strain was engineered which contains a Pbx gene variant associated with congenital heart disease in humans. Crosses were set up between strains to compare the effect of each mutation. Thus, the use of genome engineering allowed us to conduct analyses of vital transcription factors involved in heart development.