Myanmar has been enveloped in seemingly endless civil strife since their independence from British colonization in 1949. The country is comprised of a wide array of ethnic minorities, each with their respective language and culture. Myanmar’s government may publicly announce its pride at the country’s diversity, but within, human rights violations committed by the military abound. The peace process towards a federalist state is long and hard, and has seen many cycles of ceasefires and armed conflict. My time in Thailand during CHID’s Gender, Peacekeeping and Human Rights program addressed this conflict from a myriad of perspectives. As a result, I have learned about the silent heroes of Myanmar’s peacekeeping process: the community based organizations that are actively changing the power landscape of rural areas within the ethnic minority states. There are several community-based organizations operating from the Thailand-Myanmar border that are addressing and spreading awareness of the human rights violations inside ethnic states. Most importantly, they are addressing maternal and child health in high risk areas where maternal mortality rates are some of the highest in the world. Through meetings and interviews with various community-based organizations, I am exploring the relationship between family planning and maternal health programs on the ground and women’s participation in the peace process in the country overall. I am also using content analysis of reports done by the organizations, who have obtained valuable, on the ground data from remote areas within Myanmar. I am interested in whether investing in these programs and supporting this communtiy-based approach could be one possible solution to creating multilateral agreements that last in Myanmar because of the additional involvement of women in politics and leadership.

Domoic acid (DA), a common marine neurotoxin found in marine organisms such as shellfish and finfish, is gaining public attention with increasing outbreaks in the USA, Australia, China, and some countries in Europe. Most DA outbreaks are observed along coastal regions, increasing the risk of exposure by seafood consumption. However, little is known about the effects of low level prenatal exposure of DA. To address this growing public health issue, we administered behavioral and cognitive tests on 27 Macaca fascicularis infants prenatally exposed to 0, 0.075, and 0.15 mg/kg/day of DA. Their cognitive capacities were analyzed based on their speed of learning new tests using the Wisconsin General Testing Apparatus (WGTA). The WGTA requires testers to present stimuli to the infant and, depending on the response, reward the infant for a correct response. I was one of several testers that worked with the infants during testing sessions 5 days per week. I also worked with the investigators and data analysis team to analyze the results of the WGTA tests. Results from early cognitive tests of object and spatial discrimination did not indicate a statistically significant detrimental effect of DA on these basic learning tasks. This suggests that DA does not have an impact on basic discrimination learning in the early stages of life (< 1 year). However, due to the potential for delayed toxicity of DA, more complex learning and memory tests are being administered as the infants mature. The results of this study will provide insights into future research and influence policies being implemented regarding seafood consumption and food safety.

Through mapping the complexities of spatial inequality, I examined the geographic differences in economic and socio-cultural inequality across the state of Indiana. I grew up in Indianapolis, Indiana in an upper-middle class neighborhood that undoubtedly limited my ability to see inequality. Examining inequality in my home state provided me with a deeper understanding of the gap between rich and poor within the state, how Indiana fits into the growing wealth gap in the United States, and how income inequality further impacts access to education, housing, and healthcare. I collected data from the US Census Bureau for Indiana and Indianapolis, as well as the three richest and poorest cities in the state, St. John, Zionsville, Carmel, Gary, East Chicago, and Muncie. Across the state and the seven cities studied, I measured educational attainment, employment status, health insurance coverage, housing costs, and income in the past 12 months. In Indiana, less than 25% of the population over 25 has a Bachelor’s degree. Rates of health insurance coverage vary greatly across the cities studied, but are fairly consistent across racial lines within cities. Income distribution varies drastically across the state, and by race across the seven cities in this study; however, single mothers, regardless of their race or ethnicity, are far more likely to be impoverished compared to the average in each city. In the three richest cities, populations are almost entirely white, while populations in the three poorest cities are almost entirely African American. Economic differences are not the only indicator of inequality in Indiana; socio-cultural differences also underlie many aspects of poverty and inequality. Mapping how inequality varies in terms of race, gender, and location provided a stronger sense of how geography affects the distribution of wealth and resources, and who is impacted the most.

Current methods of modeling tissues rely on two-dimensional (2D) cell cultures which fail to incorporate the three-dimensional (3D) aspect of native tissues in the body and therefore cannot mimic tissue-specific conditions in vivo. The inability to accurately mimic the native properties of tissues in vitro makes characterizing physiological cell behavior challenging and limits the applications of these models. As such, the lack of sufficient in vitro tissue models necessitates the need for a more advanced engineered tissue models that accurately recapitulates the native morphology and function of cells in vivo. Previously developed in vitro platforms that attempt to model human vasculature in vivo have been limited in their ability to imitate the circumferential architecture of smooth muscle cells which surround the veins and arteries. Through the production of a more advanced vascular tissue engineered platform that accurately recapitulates biomimetic conditions of native tissue, we could better study cardiovascular biology, disease modeling, and drug-response in a dish. We propose the fabrication of an architecturally-controlled multi-layered 3D smooth muscle cardiovascular model that mimics the tubular structure of blood vessels in vivo to study structure-function relationships. Utilizing a thermoresponsive nanopatterned film, we are able to direct cell alignment and layer sheets of cells to create a circumferentially aligned 3D smooth muscle tissue model that mimics the physiology of the vascular tunica media. Furthermore, we have designed a fibrin gel casting method to produce tubes with a hollow intraluminal space that has mechanical properties that are physiologically relevant to human tissue. We aim to determine how anisotropic alignment of smooth muscle affects vascular compliance. This model is highly versatile in nature and can be functionalized with a wide variety of cell types to accommodate different tubular tissue structure throughout the human body.

Cancer metastasis, or spreading to another site, is the leading cause of cancer-related deaths. Invasive cancer cells migrate through the extracellular matrix (ECM), a meshwork of protein fibers that gives structure to tissue. These fibers normally have a random arrangement, but as a cancer cell migrates it rearranges them, leaving a trail of aligned fibers that can induce other tumor cells to follow. Tumor-specific aligned matrix topography is critically lacking in current cancer models and drug screening platforms. Here we explored the different mechanical factors that can be used to induce type I collagen, an important ECM protein, to form aligned fibers as they polymerize. Our preliminary experiments showed the effects of fluid flow induced by mechanical motion on gel formation. Collagen gels were incubated in polydimethylsiloxane molds of varying dimensions on a rocking platform to guide the flow direction and collagen fiber alignment. We then imaged the gels with a second harmonic generation microscope and analyzed the images using the MATLAB-based program CT-FIRE. The deviation between the angle of fibers and the alignment were used to determine the parameters for optimizing the method. The results suggested that the dimensions of the chamber and amount of time on a rocker affect the alignment of the collagen fibers. Further experiments will be conducted to quantify the effects of fluid flow, shear force, and surface tension on collagen fiber alignment. We plan to determine and combine two parameters which are most effective to align collagen fibers to establish an easy and reproducible method. We will further optimize the protocol to achieve uniformly aligned collagen fiber in a high-throughput manner. The tumor matrix topography specific 3D model we develop in our study will be valuable as a platform to study the behavior of migratory cancer cells and to identify novel anti-metastatic therapeutics.

Studying zebrafish embryos allows us to understand features of vertebrate embryonic development. Neuro-mesodermal progenitor cells at the very posterior end, or tailbud, of an embryo are bipotential. This is because the presence or absence of Wnt signaling commits them to either neural or mesodermal fate. Directed by environmental cues, mesodermal cells exit the tailbud, migrate anteriorward, and become somites, structural segments from which muscles differentiate. The Kimelman lab has found that Tbx16/Spadetail, a major driver of mesodermal morphogenesis, downregulates Arhgap29 and Arhgap35, members of Rho family GTPase activating proteins. This suggests Arhgap29 and Arhgap35 may be involved in mesodermal cell movement. My work in the lab is focused on finding out what roles these two genes play. I used heat shock promoter hsp70 to overexpress Arhgap29 and Arhgap35 in transgenic fish lines. Previously, our lab showed that sustained Arhgap35 affected somite morphology, and that sustained Arhgap29 also decreased the number of somites. In my experiments, I carried out in-situ hybridization in wild-type, Arhgap29- and Arhgap35-expressing embryos to examine genes regulating specification/differentiation of muscle cells and genes involved in transmembrane cell adhesion. I will present data on cell tracking and cell protrusions collected from Arhgap29- and Arhgap35-expressing embryos. These results will help me compare cell migration between Arhgap-expressing and wild-type embryos. The purpose of these analyses is to understand how these two proteins control cell movement in the embryo. In the future, I will continue to investigate cellular mechanisms underlying vertebrate posterior elongation.

During the early stages of vertebrate embryonic development, blocks of muscle tissue called somites form progressively along the anterior-posterior (head to tail) body axis. As the embryo grows in length, new somites are continuously added at the posterior end until the tail reaches its final length. Our work focuses on a subset of genes called the hox genes. These genes encode transcriptional regulatory proteins that are involved in controlling the formation of the body plan along the anterior-posterior (AP) axis. In vertebrates, these genes are present in four major clusters (A, B, C and D) and within a cluster they are expressed temporally from 3’ to 5’ of DNA, with hox13 being at the very 5’ end and thus the most posteriorly expressed hox genes. In this study we use zebrafish as a model organism. Zebrafish embryos are excellent for investigation because: 1) the genome has been fully sequenced to a very high quality allowing the use of CRISPR mutagenesis; 2) the zebrafish embryos are transparent and so very easy to study using live microscope imaging; 3) much of the early development is similar among all vertebrates including humans. The role of the hox genes during the somite-forming states has almost entirely been characterized based on the overexpression of individual hox genes in previous research. We developed a zebrafish loss-of-function hoxa13 CRISPR mutant and are investigating the roles of this gene on the formation of the body plan. My research focuses on understanding how a loss of hoxa13 gene affects cell movement as the AP axis forms using spinning desk confocal microscopy to capture cells and Imaris software to track them, and I will present the results of this analysis. We expect to observe abnormal or reversal of cell movement in the prognitor area of the tailbud.

For women to have protection from unintended pregnancy and human immunodeficiency (HIV), current lead prevention options use oral antiretroviral drugs (ARV) for pre-exposure prophylaxis (oral PrEP) along with a form of contraception. Failure to adhere to these drug therapies will increase the risk of contracting HIV or pregnancy. We have proposed to integrate drug-eluting materials onto a copper-intrauterine device (IUD) that could provide both HIV prevention and contraception. We will evaluate two methods to formulate a matrix release drug delivery system. Injection molding is a method to inject material into a mold that can be used for constructing drug-eluting medical devices with low drug degradation. For our purpose, we injected a polymer and drug combination into a mold to construct a solid slab. Whereas, electrospinning is a method that uses electric force to formulate stable and high surface-to-volume ratio nanofibers with high drug encapsulation and porosity compared to the molded slab. Both delivery systems will be used to administer ARV drugs to the female genital tract for a year. We optimized the molded slab and electrospun nanofibers technique for maximum polymer-loading, and used 3-D printing and nanofiber wrapping technique as a process for slab integration and fiber integration onto the IUD respectively. The polymer and drug combinations for both electrospun nanofibers and molded slabs were chosen to have the maximum drug-loading and stable mechanical properties. Drug release was measured in vitro to predict daily release rates out to three years. The ideal matrix release drug delivery system method for the dual HIV prevention and conception IUD is determined based on the mechanical properties and drug release rate of the polymer and system combination. We also investigated the drug delivery systems for cytotoxicity to verify dosage safety.