Health Sciences – Page 25 – UROP Spring Symposium 2021

Health Sciences

Promoting Breast and Cervical Cancer Screening among Asian American Women in West MI

Breast and cervical cancer disparities are growing issues among Michigan’s Asian American communities due to various barriers. Early detection and screening play an essential role in decreasing cancer morbidity and mortality, nevertheless, Asian American women are less likely to receive pap smears and mammograms due to language, cultural, socioeconomic, and healthcare access barriers. This reveals the pressing need for services tailored for ethnic groups to increase breast and cervical cancer screening for Asian American (AA) women in Western Michigan regions. The purpose of this study was to explore and compare the differences in perceived barriers for breast and cervical cancer screening and study the roles bilingual community health workers play in facilitating three Asian American groups. Specifically, our study includes Chinese, Vietnamese, and Nepali patients in Western Michigan enrolling in the Michigan Breast and Cervical Cancer Control Navigation Program (BC3NP). Research Questions are 1. What are the major barriers related to receiving breast and cervical cancer screening among AA women? and 2. What are the roles that bilingual community health workers in Western Michigan have in facilitating women’s enrollment into the Michigan BC3NP. Tracking form that measures demographic including insurance status, age, as well as screening status and results, will be collected. The results and conclusion of the survey are yet to be determined. The results will yield evidence-based recommendations to effectively promote breast and cervical cancer screening among AA women in Western Michigan, ultimately increasing screening rates in this population.

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Investigating How the Presence of Neutrophils Impacts Tumor Metastasis

This research is dedicated to learning about the role of neutrophils in the immune system and how they are involved in the disease progression of different cancers. 4T1 and 4T07 cell lines both originated within the same primary tumor, however, 4T7 is metastatic and the 4T07 cell line is not. When cultured in the presence of DHMs, both cell lines behave similarly which means that when NETs are absent (in vivo), the 4T1 cell line stops metastasizing.This suggests that the interaction between 4T1 cells and NETs is important for the metastasis of these tumors. We found that when cultured in vitro, 4T1 cells constitutively express/produce neutrophil chemoattractants (CXCR1 and CXCR2) while 4T07 cells do not, and when cultured in the presence of DHMs, both cell lines begin expressing/producing roughly equivalent, high levels of these chemokines.

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Developing a Novel Drug Agent for EGFR Mutant Lung Cancer Patients

Non-small cell lung cancer (NSCLC) patients affected by mutant EGFR are often treated with tyrosine kinase inhibitors (TKIs). However, new mutations in EGFR during treatment often limit the overall efficacy of these TKIs. As a result, patients suffering from EGFR mutations have been left with no long-term treatment options. In order to combat this clinical crisis, the Nyati Lab has developed a novel molecule, DPI-503, which acts as a prolonged and more effective treatment for the EGFR mutations commonly observed in NSCLCs. This molecule works to impair EGFR dimerization, degrade activated forms of EGFR, and therefore, selectively target NSCLC tumors, including those that have developed resistance to existing TKIs. The success of DPI-503 has been confirmed in over 6 different mouse tumor models. Further, both in vivo and in vitro tests have resulted in EGFR driven cancer cell specific cytotoxicity. In order to contribute to the progress of the lab, I have researched and presented information regarding EGFR biology, inhibition mechanisms, and signaling pathways as well as facts and figures detailing the role of EGFR in the success of KRAS-G12C inhibition pathways in colorectal cancers. Additionally, I have engaged in weekly lab meetings to maintain a high degree of understanding regarding lab activities and updates. Overall, the studies produced through the Nyati Lab highlight a novel method for selective targeting of mutant EGFR and indicate that DPI-503 has the potential to improve clinical outcomes for patients with pancreatic, colorectal, and lung cancers. In the future, the Nyati Lab plans to initiate IND enabling studies with the aim of beginning Phase I clinical trials for the above-mentioned patient population.

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Creating a Culture of Health at Hope Family Health Center

Authority Health recently received funding to develop and implement a Child & Adolescent Health Center at Hope Academy Charter school on Detroit’s west side. In light of this development, there was a need to establish a school wellness plan, recommending types of physical activity and nutritional services that would benefit students in the Nardin Park area. This project aimed to assess community resources, the physical environment around Hope Academy, and current nutrition and physical activity habits in order to create that physical activity and nutritional programming, integrating other community resources and providing benefit to students’ health and wellness. The methodology behind this endeavor was to conduct an environmental scan for community resources in the Nardin Park area, meet virtually on a weekly basis with parents at the school, and to gather data about physical activity and nutritional patterns from the children via surveys distributed to their parents. Survey results will be analyzed to compare student habits to suggested physical activity and nutritional guidelines by accredited national health organizations. The results will then be used to develop programming that aims to promote physical activity and nutritional improvements in line with established guidelines, that includes the integration of community resources, discovered through the environmental scan, for provision of programming.

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Trends in the Market Status of Cannabis by US Population

In 1996, California became the first state to legalize the medical use of cannabis. In the roughly 25 years since then, nearly 35 states have passed legislation to make medical cannabis legal. A similar state-level trend for the legalization of recreational marijuana started in 2012. The population eligible for medical marijuana use has been growing, as has the population affected by the legalization of recreational cannabis. In order to determine how quickly these markets are changing and to help pinpoint years that may have been particularly influential, data was gathered that tracks adult population by state and year. This data was assembled in 2 separate groups; one where states have legalized medical marijuana, and another where states have legalized recreational marijuana (often in addition to medical). The trends observed demonstrate that the population prohibited from any type of marijuana use – recreational or medical – has been decreasing, as the populations for medical use and recreational use have been increasing fairly steadily, with large population jumps corresponding to new states’ legalization, in 2014 and 2016 in particular. By 2016, more of the US population lived in states where cannabis was legal for medical use than where it was prohibited.

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The role of FADD in G1 to S cell cycle transition

Our research focuses on the role of FADD in the cell cycle. FADD is known to play an important role in cell death, signaling the cell to enter apoptosis. We are proposing another role of FADD in cell cycle regulation, specifically in the transition of cells from G1 to S phase. To evaluate the role of FADD we observed the level of known factors in cell cycle regulation. Certain proteins, such as Cdt1 and Geminin are only active at specific times of the cell cycle. By adding reporters to these proteins, we were able to track what stage a specific cell was in. We used live-cell microscopical imaging to track the cells as they progressed through the cell cycle. Cells will appear as different colors based on the amount and the type of protein they are expressing. In G1, cells will appear green, in S phase they will appear red, and cells in M/G2 phase will appear orange. The results from these experiments have shown that in cells where FADD is silenced, G1 to S transition is delayed for up to 22 hours. Some cells never pass the G1 to S checkpoint and are stuck in G1 phase. These are very promising results and line up with the assumption that FADD plays a critical role in cell cycle transition. The next step in our research is to collect more data on factors that might influence and regulate FADD. Additionally, we want to examine the effectiveness of several inhibitors, developed as cancer drugs, and determine if, when FADD is blocked, they lead to better outcomes.

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Prediction and Assessment of Acute Respiratory Distress Syndrome: Effects of Assumptions in Imputation Methods

Acute respiratory distress syndrome (ARDS) is a life-threatening lung condition that is under-diagnosed in the clinical setting. With a 43% hospitalized mortality rate, it is critical that diagnosis is made in a timely manner for ventilation strategies to be instituted. The Biomedical and Clinical Informatics lab at U-M has been developing a real-time clinical decision support system to detect ARDS through machine learning methods, specifically a modified support vector machine. A clear distinction from other ARDS-related support systems is the use of “privileged information” “” data accessible at the time of training themachine learning model but which is not available in deployment. In the context of this project, we define privileged information to consist of CT scans, which are required for ARDS diagnosis. Such information is not available to the clinician during the early period of a patient’s stay. Therefore, by incorporating such privileged information, we expect the model to lead to faster ARDS diagnosis in clinical practice. This research investigates the electronic health record (EHR) pipeline of the model. With inconsistencies and missing values, some EHR features are absent from one patient while present in another. We aim to improve the model’s accuracy in ARDS detection by testing a unique data imputation method against different machine learning models and settings. Specifically, missing values will be imputed under the assumption that data is not missing at random but as a result of the clinician’s decision that the patient had optimal health in such cases. This method is implemented by imputing data taken from the Michigan Medicine’s established reference ranges when possible. The proposed method will be compared with different machine learning models and feature reduction techniques.

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Precision Medicine for Patients with Glomerular Disease

Introduction: Nephrotic syndrome is a rare, chronic disease in children that results in severe edema, poor quality of life, extended treatment with immunosuppressive medications, increased risk for acute kidney injury, thromboembolism, hypertension, growth disturbances, hospitalizations, and mortality. Beyond long-term corticosteroid use, therapies are used off-label and have significant toxicities. 50% of cases will develop frequently relapsing or steroid-dependent disease (FR/SDNS). To improve treatment options for these patients, the UM Pediatric Nephrology Research team is developing clinical trials. Objective(s): To inform clinical trial design for FR/SDNS, we 1) elicited input from a clinician-investigator stakeholder group on endpoint prioritization and 2) conducted a systematic literature review to aid in the development and use of FR/SDNS endpoints in trial design.

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The Effects of Neutrophils and DHMs on Tumor Metastasis

In 2017, researchers at the Cold Spring Harbor Laboratory in New York discovered a relationship between metastasis and NETs (neutrophil extracellular traps). They found that when neutrophil infiltration, or the production of NETs by infiltrating neutrophils, was inhibited; the 4T1 cell line, a cell line that usually metastasizes, did not metastasize. The 4T1 cell line and the 4T07 cell line share a common genetic background. The cell lines produce different amounts of CXCR-2 ligands (substances that form a complex with something for a biological purpose) in vitro, but similar amounts when cultured in the presence of DHMs (DNA histone mesostructures). The main question is what mutations are present in the 4T1 cells that are not present in the 4T07 cells that enable it to metastasize. The team began analyzing data provided by Siegel Lab (McGill in Canada). The relative intensity of each gene was identified in separate replicate experiments. Each research member compiled data on multiple signaling pathways to try and identify what pathway causes the 4T1 to metastasize. The team identified 39 different pathways that could be potential influencers on 4T1 metastasis; however, results are still pending as to which pathways impact 4T1 metastasis. From these identified pathways, experiments involving inhibitors for each individual pathway will be conducted in the future and the results will be presented.

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The Effects of Neutrophils and DHMs on Tumor Metastasis

In 2017, the Cold Spring Harbor Laboratory in New York discovered a relationship between metastasis and NETs (neutrophil extracellular traps). They found that when neutrophils were blocked by NETs, the 4T1 cell line, a cell line that usually metastasizes, did not metastasize. The 4T1 cell line and the 4T07 cell line share a common genetic background. The cell lines produce different amounts of CXCR-2 ligands (substances that form a complex with something for a biological purpose) in vitro, but similar amounts when cultured in the presence of DHMs (DNA histone mesostructures). The main question is what mutations are present in the 4T1 cells that are not present in the 4T07 cells that enable it to metastasize. The team began analyzing data provided by Siegel Lab (McGill in Canada). The relative intensity of each gene was identified in separate replicate experiments. Each research member compiled data on multiple signaling pathways to try and identify what pathway causes the 4T1 to metastasize. The team identified 39 different pathways that could be potential influencers on 4T1 metastasis; however, results are still pending as to which pathways impact 4T1 metastasis. From these identified pathways, experiments involving inhibitors for each individual pathway will be conducted in the future and the results will be presented. Dr. Priyan Weerappuli Mentor Signature

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