Air pollution due to traffic causes many human health problems including neurological disorders. Recently, compelling evidence from the literature has demonstrated that gut microbiome is a newly discovered organ that critically regulates the neurodegenerative disorders including Alzheimer’s disease (AD) via remote-sensing mechanisms. One of the major classes of microbial metabolites are the secondary bile acids. My research focuses on the relationship between TRAP (Traffic-Related Air Pollution) and bacterial metabolism of bile acids that might have significant implications on human health. Male and female wild Type (WT) and transgenic (TG; over-expresses two human AD risk genes [mutant amyloid precursor protein and presenilin-1]) rats were exposed to TRAP or filtered air (FA) for different time points. I focused on rats up to 10 months old that were exposed to TRAP or FA for up to 9 months and from their intestinal contents I extracted bile acids, DNA and RNA to compare which factors might affect gene expression. Bacterial gene and taxa abundance were measured by quantitative PCR (qPCR) and statistically analyzed for significance. Two-way ANOVA analyses were conducted separately among male and female rats; only male rats showed significant changes by qPCR. Exposure to TRAP increased levels of Lactobacillus reuteri in WT males, but conversely decreased L. reuteri in TG males. By understanding different factors affecting bacterial metabolism of bile acids, we are exploring if this could possibly affect human health as well. This can potentially help clinicians and environmentalists to improve clinical outcomes and policies regarding traffic-related air pollution.

Maternal exposure to persistent environmental toxicants polybrominated diphenyl ethers (PBDEs) is associated with many human diseases, notably hepatotoxicity, thyroid disorders, and reproductive toxicity. PBDEs, previously seeded into manufactured products as flame retardants in the United States, were phased out during the 2000s. A 2017 study of women in California showed modest average annual percent increases in serum concentrations of PBDEs. Accordingly, the gut microbiome is increasingly recognized as the “second genome”, impacting crucial health-related factors like host xenobiotic biotransformation and energy homeostasis. Persistent dysbiosis may contribute to altered susceptibility of disease in adulthood. My goal for this study was to test the hypothesis that perinatal exposure to BDE-47, a common PBDE congener that can cross the placenta and enrich in breast milk, modifies the developmental trajectory of gut microbiota. Pregnant Wistar rats were orally exposed to BDE-47 (0.2mg/kg) from gestational day 8 to postnatal day (PND) 21. Fecal samples were collected from mothers at PND21 and male pups at PND65 and 120. I isolated Microbial DNA using 16S rDNA sequencing (n=5~9/group) and analyzed my data through QIIME. Perinatal BDE-47 exposure had minimal effect on the richness of gut microbiota in PND65 pups and mothers, but profoundly increased richness of gut microbiota in PND120 pups. In PND65 pups, only 4 taxa were persistently regulated by perinatal BDE-47 exposure. Interestingly, the effect of perinatal BDE-47 exposure was evident in PND120 pups, with an increase in 3 taxa in the Lactobacillales order and 11 taxa in the Clostridiales order. Targeted metabolomics has confirmed alterations of distinct microbial metabolites (short-chain fatty acids and secondary bile acids) corresponding to BDE-47-induced dysbiosis. In summary, the present study showed that perinatal BDE-47 exposure modified the developmental trajectory of the offspring’s microbiota, possibly producing delayed onset of diseases in adulthood.
 

Marine mammal strandings can serve as an indicator of marine ecosystem and mammal population health, providing an opportunity to learn about the life of individual animals prior to their deaths. Existing stranding networks are focused on response to opportunistic reports of stranded or beached marine mammals, which limits their usefulness in establishing baseline data. The Coastal Observation and Seabird Survey Team (COASST) engages volunteers along the western coast of the United States in collecting and reporting data for two effort-based programs, beached birds and marine debris. Looking to the future, COASST hopes to complement information gathered by marine mammal stranding networks by expanding their effort-based surveys to include marine mammals. COASST has already begun this process by asking volunteers to report sightings of marine mammals along with pictures of their beached bird or marine debris finds. These pictures can be used for species identification, and by looking at these photos in correspondence to other survey data such as region, beach, and survey date we can learn about species distribution along the western coast of the United States. We found at least 300 beached pinnipeds, through photo identification we were able to place them into at the least the families Otariidae or Phocidae. Using current literature on marine mammals, pinnipeds specifically, and their identifying characteristics, I aim to map pinniped species distribution and locate hotspots to ultimately test a pinniped species identification key that will be used by COASST volunteers. With this distribution and hotspot identification we will be able to idenify whether pinnipeds follow already established beaching patterns of beached birds or if they differ. These differentiations could lead to more information about the death of marine mammals and allow future research on the death of these animals in more focalized areas. 

Carbon dioxide concentrations have been on the rise since preindustrial times due to anthropogenic emissions. Understanding how past climates have responded to changes in the atmosphere is important to understand how our current climate will react to changes in our present-day atmosphere. Soil carbonates record the temperature at the time of their formation in their stable isotopic composition (called clumped isotope geochemistry). Ancient soil carbonates can record the temperature and allow us to better understand paleoclimates. Understanding what time of year soil carbonates form allows us to better interpret the temperature being recorded. The timing of changes in soil moisture is likely one of the most important environmental factors to consider. We test whether soil carbonates form during soil drying events using soil moisture and temperature data measured remotely by a satellite called Soil Moisture Active Passive (SMAP). This satellite has been gathering near-surface soil moisture data globally since 2015 at 35-65 km resolution. We compare the air temperature of the month with the greatest net negative soil moisture content month (determined from the satellite data) to the measured growth temperature of soil carbonates (estimated through geochemistry). We first compare the month of drying of three locales in North America, then extend the analysis globally to all locations for which soil carbonate clumped isotope data exist. Preliminary results suggest that the temperature of the month with the most drying agrees with formation temperature we estimated from clumped isotope geochemistry within one degree for a site in Nebraska and within seven degrees for a site in Wyoming. These results suggest that soil drying promotes soil carbonate formation in some environments. By using soil carbonates to explain past climates, we will improve temperature change estimates, which will help improve climate models for the future.

Chimeric antigen receptor (CAR) T-cell therapy is the latest treatment option available for those suffering from certain forms of cancer such as lymphoma and leukemia. These engineered cells are able to recognize specific proteins found in tumors, and subsequently induce CAR-T cell proliferation, cytokine secretion, and lysis of the cancerous cells. Despite its promise, a percentage of patients who receive this treatment develop a range of neurotoxic symptoms. My research project tests the hypothesis that endothelial activation of vascular tissue in the brain, which would allow for increased permeability of immune cells through the blood-brain barrier, is contributing to the development of these clinical symptoms. Using a technique called immunohistochemistry, I used the antibodies claudin-5 and cd31 to fluorescently label tight-junction proteins and adhesion molecules of endothelial cells from brain tissue harvested from a developed mouse model. This mouse model received CAR-T cell injections and underwent behavioral testing to confirm the presence of neurotoxicity symptoms. I then used microscopy skills to visualize the labeling of the endothelial cells and proteins. If my hypothesis is correct, I expect to see a quantifiable decrease in the number of cerebral tight-junction proteins connecting endothelial cells along the blood-brain barrier, as compared to negative control tissue that received no CAR-T cell injections. In order to make these comparisons, I will use a software program such as Image-Pro Premier software (Media Cybernetics) to help me quantify the positive fluorescence labeling of endothelial cell proteins and adhesion molecules in both the control and experimental tissue. Tissue with less tight-junction proteins and adhesion molecules would permit the influx of foreign particles into the CNS. Understanding the cause of CAR T-cell related neurotoxicity will be first step in promoting prevention and increasing the effectiveness of this new cancer immunotherapy.

Gut Microbiome is increasingly recognized as a pivotal player in toxicological responses, thus dysbiosis or microbial imbalance may worsen chemical-induced adverse outcomes such as inflammation, metabolic syndrome, and cancer. Early life exposure to environmental contaminants may produce long term toxicities in adulthood, and little is known to what extent early life exposure to environmental contaminants modulate the gut microbiome beyond adulthood. Therefore, this study tested the effects of perinatal exposure to 3 human health relevant environmental contaminants (BDE-47, TBBPA, and BPS), on the composition and functions of the gut microbiome of perinatally exposed adult male mice. CD-1 mouse dams were orally exposed to vehicle (corn-oil, 10ml/kg), BDE-47 (0.2mg/kg), TBBPA (0.2mg/kg), and BPS (0.2mg/kg) once daily from gestational day 8 to the end of lactation (postnatal day 21). Feces from male pups were collected at 12-weeks of age (n=14-23/group). Microbial DNA was isolated, subjected to 16rDNA sequencing, and analyzed using QIIME. Microbial biomarkers for each chemical exposure were predicted using LefSe. Microbial functions and key taxa that drive functional changes were predicted using PICRUSt and FishTaco, respectively. None of the 3 chemicals markedly altered the overall richness of the gut microbiome in adult male pups. However, principle coordinate analysis showed a distinct separation among different exposure groups, and especially between BPS and vehicle exposure groups. A total of 73 taxa were persistently altered by at least 1 chemical exposure, among which 12 taxa were commonly regulated by all 3 chemicals. The most representative microbial biomarkers for each exposure condition were Clostridiales for vehicle, S24-7 for BDE-47, Rikenellaceae for TBBPA, and Lactobacillus for BPS. Together, these observations suggest early life exposure to these human health relevant environmental contaminants produce persistent gut dysbiosis in adult male offspring, leading to functional shifts that may play important roles in regulating certain diseases of the host.