Health Sciences – Page 30 – UROP Spring Symposium 2021

Health Sciences

Alaska Native Health Research

Compared to the lower 48 states, Alaska faces unproportional rates of suicide related death and injuries, especially among the Alaskan Native (AN) youth. From the effects of colonialism to social changes, there are numerous issues plaguing Native youth today, putting them at higher risk of suicide compared to their White counterparts. Another aspect of life that puts youth at higher risk is access to firearms, which are commonly found within rural Alaskan homes. Research is being done to learn about safe firearm storage practices within people’s homes in order to increase safety and reduce the risk of firearm related accidents and suicide. The short intervention we are developing uses motivational interviewing to increase adult family members’ safe firearm storage practices in their households. Building on information generated through local household surveys about home firearm storage practices, communications, responsibilities and preferences, we will develop motivational Interviewing guides. This project will identify key motivations and ways of engaging adults in a universal intervention to improve safety practices related to firearm storage. This project integrates previous motivational interviewing research and guides to be used to adapt our brief intervention–the family safety net–to the local priorities, motivations, values and local language use and norms.

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Connections Between Cell Signaling, Neutrophils, and Tumor Metastasis

Triple negative breast cancer (TNBC) is a type of breast cancer that is defined by the absence of estrogen receptors, progesterone receptors, and the low expression of HER2. The combined absence of these markers, historically, led to TNBCs having poorer prognosis due to the lack of therapeutic targets. Recent research reported by the Egeblad group (Cold Spring Harbor Laboratory) was able to identify that neutrophil extracellular traps (NETs), a pathogen trapping structure comprised of DNA, histones, and various other neutrophil-associated proteins, typically produced in the presence of a pathogenic infection, are prompted to form by metastatic breast cancer cells in the absence of an active infection. By studying the effect of inhibiting neutrophil infiltration, NET production, and of breaking down NETs within a short time through the use of DNase I treatment in vivo; the Egeblad group demonstrated that metastasis of the traditionally-metastatic 4T1 cell line could be prevented/delayed simply by targeting the interaction between tumors and NETs – thereby establishing NETs as a potential therapeutic target for the treatment of TNBC. Using the same 4T1 and 4T07 cell lines examined by the Egeblad group, we have recently demonstrated that these two cell lines constitutively produce different levels of CXCR-2 ligands in vitro when grown in control/untreated conditions; but produce similar levels when cultured in the presence of a NET-like biomaterial we have developed that we refer to as DNA-histone mesostructures (DHMs). Because 4T1 and 4T07 cells are derived from the same spontaneously-occurring parental tumor, this difference in constitutive expression poses interesting questions: what mutational differences may be present in 4T1 cells (but not in the 4T07 cells) that contributes to their constitutive production of CXCR-2 ligands (which act as neutrophil chemoattractants and induce the production of NETs by infiltrating neutrophils), and what similarities exist between these cells that may underlie their shared response to DHMs in vitro. To address these questions, we have chosen to take a multi-faceted approach that examines transcriptomic data from 4T1 and 4T07 cells grown in vitro (+/- DHMs) and in vivo (+/- DHMs), conducting comprehensive literature reviews on cancer-related intracellular signaling pathways to see what genes and intracellular factors may shed light upon the source of the intrinsic difference between these cell lines.

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Connections Between Cell Signaling, Neutrophils, and Tumor Metastasis

Triple negative breast cancer (TNBC) is a type of breast cancer that is defined by the absence of estrogen receptors, progesterone receptors, and the low expression of HER2. The combined absence of these markers, historically, led to TNBCs having poorer prognosis due to the lack of therapeutic targets. Recent research reported by the Egeblad group (Cold Spring Harbor Laboratory) was able to identify that neutrophil extracellular traps (NETs), a pathogen trapping structure comprised of DNA, histones, and various other neutrophil-associated proteins, typically produced in the presence of a pathogenic infection, are prompted to form by metastatic breast cancer cells in the absence of an active infection. By studying the effect of inhibiting neutrophil infiltration, NET production, and of breaking down NETs within a short time through the use of DNase I treatment in vivo; the Egeblad group demonstrated that metastasis of the traditionally-metastatic 4T1 cell line could be prevented/delayed simply by targeting the interaction between tumors and NETs – thereby establishing NETs as a potential therapeutic target for the treatment of TNBC.

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Genetic Impact on Low Diversity Microbiomes in Patients with Inflammatory Bowel Disease

Inflammatory Bowel Disease (IBD), a term that is used to generalize Ulcerative Colitis (UC) and Crohn’s Disease, is a disorder that involves chronic inflammation in the digestive tracts. UC is restricted to the colon, while Crohn’s disease can involve all segments of the GI tract. The pathogenesis of IBD is still unclear but several proposed mechanisms are being investigated which lead to a loss of homeostatic host-microbe interaction in the GI tract. Our study focuses on one of those mechanisms whereby a mutation in a gene that encodes an NADPH oxidase called Duox2 might lead to a loss of host-microbe homeostasis in the gut. In addition, we aim to better understand the possible environmental and hereditary factors that may contribute to IBD. Our study aimed to recruit 100 sibling pairs to take a survey that asked questions about diet, sleep, exercise, and their living environment. One of the siblings had IBD while the other was a control subject. Each sibling pair had a first degree relative with IBD, indicating a possible genetic component (e.g., Duox2 mutation). There was a parallel study conducted in Taiwan to also compare differences in ethnicity. Through our survey, we predicted that results will show trends among families who have IBD. The second phase of the study, identified patients who may be more likely to have a mutation in the Duox2 gene by screening for congenital hypothyroidism known to share a common genetic risk gene in Duox2. By collecting a blood and stool sample from families, we predict that we will be able to better understand the determinants of genetics, environment, and gut microbiota in the pathogenesis of IBD.

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