Health Sciences – UROP Summer Symposium 2021

Health Sciences

Tissue Crosstalk in Joint Injury

Post-traumatic osteoarthritis (PTOA) is a serious disease that results from joint injury. It is characterized by cartilage deterioration, synovial inflammation, and the formation of abnormal bone growths. The Wnt signaling pathway is an important biological process by which cells respond to external stimuli. Overactive Wnt signaling within the joint is known to take part in the progression of PTOA. R-spondin 2 is a protein secreted by cells into the extracellular matrix that functions as an agonist for the Wnt signaling pathway. While R-spondin 2 is known to activate Wnt signaling, little is known about its role in PTOA. Here, we aimed to better understand the contribution of R-spondin 2 in the overactivation of Wnt signaling and how this process contributes to PTOA pathology. We hypothesized that, given the pathological role of unchecked Wnt signaling in OA, adding additional R-spondin 2 would exacerbate joint degeneration in a mouse model of PTOA.

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Analysis of COVID-19 Vaccine-associated Blood Clot Adverse Event Case Reports

Background: While COVID-19 vaccines are generally safe, they are occasionally associated with various adverse events (AEs). Recently the Janssen COVID-19 vaccine (i.e Johnson and Johnson vaccine) has been reported to be significantly associated with blood clot, or thrombosis. The CDC/FDA Vaccine Adverse Event Reporting System (VAERS) has continuously collected various vaccine adverse events reported from the USA.

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Investigating the role of glucose metabolism in oncogenic STAT3 signaling in colorectal carcinoma

Via the article Colorectal cancer statistics, 2020, approximately 147,950 individuals were diagnosed with Colorectal Carcinoma (CRC) and 53,200 died from the disease in 2020. CRC, like many other cancers, activates signaling pathways to become more aggressive and deadly. STAT3 (signal transducer and activator of transcription) is a signaling pathway that promotes cell growth during normal development and cancer. The Shah lab has previously discovered that the STAT3 pathway plays a major role in promoting CRC growth. Interestingly, some CRC cell lines, like SW480 and HCT116, have high levels of p-STAT3 (a marker of STAT3 pathway activation) at baseline (without ligand stimulation). The Shah lab also found that glucose deprivation, but not the removal of amino acids or serum, decreased the activation of the STAT3 pathway in HCT116 and SW480 cells. We wanted to further explore the STAT3 signaling pathway in CRC cells and the interactions between signaling and metabolites in the CRC environment.

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The experiences of rheumatic disease patients when deciding to get the COVID-19 vaccine: a qualitative analysis

Background: Little is known about how the COVID-19 vaccine affects people with rheumatic diseases. Though rheumatic and musculoskeletal diseases (RMDs) are relatively common, patients with RMDs were not included in randomized controlled trials for COVID-19 vaccines. People that live with rheumatic conditions must consider how to handle immunomodulatory medications during the vaccine cycle and the tradeoffs they may be making between their condition, immune response, and possible side effects. We aim to describe the factors considered by this population when deciding to get the COVID-19 vaccine.

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Characterization of the Tumor Immune Microenvironment in Sarcoma

Intro: In recent years, the advancement of technology and science has led to better cancer treatments, which subsequently has resulted in increasing the chance of cancer patient survival. Immunotherapy, one of the more recent promising treatment options, works by enhancing one own’s immune system to fight cancer. Immunotherapy using anti-PD1 and anti-CTLA4 checkpoint blockade has been very successful in treating patients with some malignant tumors such as melanoma, which previously did not have a clear effective systemic treatment option. Sarcoma is an overarching category of rare tumors that originates from soft tissues or bones at various parts of the body. Liposarcoma is one of the most common types of sarcoma, with the most common biological type being well-differentiated and dedifferentiated liposarcoma (WDLPS and DDLPS respectively). WDLPS and DDLPS are most effectively treated by surgery, yet even after a complete resection of DDLPS, 60% of patients develop local recurrence and 25% develop distant metastasis (secondary phase of malignant growth) within 5 years of diagnosis. The response rate to conventional chemotherapy is low so that 60% of patients with DDLPS eventually die from the disease. Despite the promising developments in immunotherapy, research focusing on the immune biology of sarcoma has been slower than other tumor types. Recently, there have been some promising reports of response to immunotherapy in a small number of liposarcoma patients, hence, there is an unmet need to better understand the tumor immune microenvironment in liposarcoma.

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Progression of Cancers Driven by Liver Metastasis

Adedoyin Adebayo Pronouns: She/Her/Hers UROP Fellowship: CCSFP, Oakland Community College Research Mentor(s): Michael Green, MD, PhD and Amanda Huber, PhD Research Mentor Institution/Department: Michigan Medicine and Ann Arbor Veterans Affairs, Department of Radiation Oncology, Department of Microbiology and Immunology Department of Radiation Oncology Presentation Date: Wednesday, August 4th Session: Session 2 (4pm-4:50pm EDT) Breakout Room:

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Developing Novel Methods to Study the Longitudinal Effects of Chronic Stress in Mice

Mental illnesses such as depression and anxiety affect millions of Americans every year, and have been known to be related to stress exposure. To examine the link between the development of these disorders in mice and stress, prior research primarily examines the correlation between exposure to various stress paradigms, such as Chronic Social Defeat Stress (CSDS) and Chronic Unpredictable Stress (CUS), on various metrics collected shortly after exposure to these paradigms. Because the majority of this research has focused on acute impacts of stress exposure, however, there is a gap in the literature regarding the longitudinal effects of this stress in mice, which could help create a better model of how stress influences the development of mental disorders in clinical settings.

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Role of the MYRF transcription factor in retinal development

Myrf is a transcription factor that is essential for proper development of the retinal pigmented epithelium (RPE) and the underlying retina. We have previously analyzed mice with a conditional deletion of Myrf in the RPE and identified resulting downstream genetic changes leading to loss of RPE and impaired vision (Garnai et al., 2019). We also identified secondary defects in the retina, loss of rod and cone photoreceptors. As the etiology of these defects is unclear, we used single cell sequencing (scRNAseq) to identify the gene expression changes associated with loss of MYRF in the RPE (Rxcre;Myrffl/fl) at various stages during embryonic and postnatal development. We hypothesize that deletion of Myrf in the RPE leads to secondary transcriptional changes in the retina that impact vision.

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Elucidating the Physiological function of human B12 trafficking protein CblD

Mutations in the mmadhc gene are responsible for the cblD-type defect in vitamin B12 metabolism. To better understand the role of the CblD chaperone protein in the B12-trafficking pathway, we propose to transfect human cells with expression vectors for epitope-tagged wild-type or mutant CblD to study how patient mutations impact localization and affects B12 metabolism. My short-term goal has been to generate the expression vectors and help establish the cytoplasmic versus mitochondrial localization of CblD.

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Restoration of Gut Barrier Protein Expression in Cytokine/LPS induced Inflammation in Colonoids

Background information: Aquamin is a multi-mineral product obtained by mineralized remains of red marine algae that is rich in calcium, magnesium and 72 additional minerals and trace elements. In current studies, it has been shown that Aquamin aids in gut barrier structure along with the function of colonoids (3D tissue culture) derived from colon biopsies of healthy subjects. It is critical that a colonic barrier is intact for the gastrointestinal health of individuals. Colonic barrier dysfunction has been a feature of inflammatory bowel diseases, such as ulcerative colitis and Crohn’s disease. Barrier dysfunction could be a result of toxic insult or inflammatory attacks on epithelial cells which line the colon, although now it is being recognized that tissue could be subject to injury or inflammation due to pre-existing weakness. If prolonged, this injury and chronic inflammation can lead to the development of colon cancer. Therefore, strengthening the colonic barrier is critical. Through experimentation, it will be determined if Aquamin can restore barrier expression in cytokine/ lipopolysaccharide (LPS) induced inflammation in normal colon tissue derived colonoids.

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