The enteric nervous system (ENS) consists of neurons and glia that control motility, secretions, and blood flow within the gastrointestinal tract. Using the zebrafish, Danio rerio, as a model we aim to understand ENS development and how this process might go array in disorders such as Hirschsprung’s, in which children are born lacking neurons in portions of their gastrointestinal tract. The number of markers for enteric glia is relatively small and many of the current immunohistochemical approaches are confounded by the uncertainty of cross-reactivity patterns between species. In preliminary experiments using established glia markers, we obtained unexpected results identifying glia in mutants lacking the ENS, suggesting a lack of glia marker specificity, or the presence of an uncharacterized subpopulation of glia in our mutants. To distinguish between these possibilities, we have cloned other markers to examine glia populations in normal larvae and larvae with defects in ENS development.

Influenza A virus (IAV) is a significant threat to profitability in the swine industry. Although vaccines can prevent the damage and spread of the pathogen, changes in the antigenic properties of the virus due to evolution may cause the virus to escape the immune response. Identifying key amino acids on the hemagglutinin (HA) protein that significantly contribute to antigenicity is important for understanding how IAV adapts in response to immune pressures so more effective vaccines can be developed. In this study we took antigenic distance data obtained by hemagglutination inhibition assays from 30 H1 subtype influenza virus strains and combined it with amino acid sequence data from the HA of the same isolates. We plotted these two variables against each other to obtain linear relationships between antigenic and genetic similarity of the viruses. We then compared amino acid differences between outlier comparisons using a threshold of two antigenic distance units above the linear fit and determined the most represented positions among all outliers. We found six amino acid positions on the HA had changes that were associated with over 50% of the outlier comparisons. These results significantly contribute to the framework of H1 IAV characterization for disease prevention efforts.

As a developing country with a population surpassing 1 billion, India faces a myriad of challenges in securing the access and provision of quality healthcare services. To develop my understanding of the multi-dimensional health system of India, I traveled to rural Maharashtra for a two month program. I shadowed doctors in privately-owned clinics, government-run centers and non-profit organizations, visited a consultation and treatment center for those living with HIV/AIDS, and traveled to remote villages with a free mobile clinic. I developed a portfolio documenting my daily log of hours, weekly activities and personal reflections. My time in the general consultation clinics contributed greatly to my knowledge of national vaccination strategies, diagnostics, treatment, regional prevalence of infectious diseases, and challenges faced in securing effective patient interactions at each of these stages. The conditions I most commonly observed were tuberculosis, malnutrition, and respiratory, gastrointestinal and dermal infections. By stepping beyond textbooks and personally facing the conditions of vulnerable communities in rural India, I witnessed the crowded populations, hazardous housing, poor sanitation, and insufficient infrastructure that perpetuate the spread of infection and disease. My research cemented the reality and complexity of healthcare problems in developing countries, concluding that future solutions cannot be successful without addressing the intertwined epidemics of poverty and education.

Stem cells are a promising option for human medical therapy. While pluripotent embryonic stem cells have an almost unlimited differentiation potential to become any type of cell, multipotent adult stem cells have a much more limited ability to differentiate. In order to better understand how adult stem cells choose their fate, two main factors were investigated: intrinsic versus extrinsic influences. This was accomplished by implanting rat adult hippocampal progenitor/stem cells (AHPCs) - which normally differentiate into neurons, astrocytes, and oligodendrocytes - into zebrafish embryos during the blastula stage, an environment with almost unlimited potential for stem cells. These embryos were then allowed to grow to three or five days post-fertilization (dpf), at which point they possess a developed nervous system and are free-swimming. The fish were then imaged using fluorescence microscopy to monitor the fate and localization of the AHPCs in relation to the embryo. The results showed a majority of the AHPCs migrating to the outer eye region (38.5%), central nervous system (26.7%), and superficial skin layer (20.7%). Immunolabeling procedures to identify differentiated cell-types revealed the highest percentage of transplanted AHPCs were TuJ1-labeled (73.4%), which distinguishes immature neurons. No significant difference in AHPC survival between 3 dpf and 5 dpf were found. This preliminary analysis reveals that these brain stem cells are likely influenced by intrinsic cell machinery - regulation of gene expression - than their environment when choosing their fate. Through this knowledge, adult stem cells and their cell regulation behaviors can be further investigated to potentially find similar drug options that may mimic the regulation of their expression.