Health Sciences

Culturally Tailored Messaging for Hispanic Youth in an mHealth Intervention

Background: Obesity is prevalent among adolescents in America, which puts millions of youth at a risk of developing chronic diseases such as diabetes, and liver disease which can lead to shorter life spans. The prevalence of excess weight among Black and Hispanic youth is particularly high compared to Caucasian youth (40% vs 38% vs 31% respectively). Contributing to this higher risk of obesity for minority youth is the fact that many Black and Hispanic youth live in families with low-socioeconomic status (65% and 62% respectively). The use of mobile health applications incorporating personally relevant content such as culturally tailored messages and images, is a promising means of helping Black and Hispanic youth achieve and maintain a healthy weight. We sought to examine the correlation, if any, between Hispanic youth’s ethnic identity and their image and language preferences used in a health app to prompt Hispanic youth to make healthier choices at fast-food venues.

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Understanding the Role of Trk Receptors in Neutrophils and Tumor Metastasis

smhilal

Neutrophils, immune cells that fight infection, can produce neutrophil extracellular traps (NETs), which are DNA meshes of the neutrophil cell. These NETs function by trapping pathogens and aiding in the immune response. However, NETs produced by neutrophils in the tumor microenvironment can promote cancer metastasis. Breast cancer metastasis is associated with very high mortality rates, and by studying the mechanism associated with NETs in promoting breast cancer metastasis, a potential therapeutic target may be identified. Two mammary cell lines were utilized in this study: 4T1 and 4T07, of which only 4T1 tumor cells metastasize. 4T1 tumors were observed to contain greater levels of infiltrating neutrophils than 4T07 tumors, and, consistent with this idea, 4T1 tumor cells express higher amounts of the CXCL1/CXCL2 chemokines, which act to recruit neutrophils. When neutrophils were prevented from making NETs, 4T1 cells stopped metastasizing, indicating the significant role NETs play in metastasis. Due to the complexity in NET structures, DHMs (DNA-histone mesostructures) were synthesized to establish controls and simulate NETs in vitro. By culturing 4T1 and 4T07 cells with and without DHMs, we intend to produce data that may aid in identifying a mechanism through which 4T1/4T07 cells interact with NETs. We also intend to study the role Trk A, B, and C receptors play in the production of chemokines, which act as neutrophil recruiters. This may lead to the development of treatments that target the recruitment of neutrophils, and thus potentially mitigate metastasis.

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Understanding the Role of Neutrophil Derived Material and Inflammation in Tumor Metastasis

changea

There is a known neutrophil-derived material called Neutrophil Extracellular Trap (NETs), made of DNA fibers, histones, and granular antimicrobial proteins, which is secreted by neutrophils to physically ensnare pathogens and fight infections. The presence of NETs in a cellular environment is known to alter protein expression. However, it is difficult to research its other functions in a cellular context because it is expensive to isolate a substantial amount of NETs from cells. We are employing a synthetic biomaterial, known as DNA-Histone mesostructure (DHMs) which mimics structural and functional properties of NETs and assessing whether it promotes the production of CXCR-2 ligands through the same pathways as NETs do. CXCR-2 activity is important for cancer metastasis, and if CXCR-2 ligand production is reduced by inhibiting DHM activity, then there is the possibility of inhibiting metastasis of cancers that might otherwise be the result of NET activity. The 4T1 and 4T07 cell lines are cultured in the presence/absence of DHMs, and protein levels of different pathways, as well as cytokine and mRNA levels in solution, are measured, which will be compared to data of previous cultures of the 4T1 and 4T07 cultured in the same media contents but with the presence/absence of NETs. We expect that DHMs will affect the cytokine production and the expression of the genome and proteome of 4T1 and 4T07s in the same way that NETs do. Should our hypothesis be correct, it would suggest DHMs may be used as a screening tool to identify the risk of metastasis in certain tumor lines and to test pharmaceuticals capable of inhibiting NET-related interactions.

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Suppression of Heterotopic Ossification Using a TAK1 Inhibitor

ihgeorge

Heterotopic ossification (or HO) is the abnormal growth of bone in soft tissues, such as muscles, tendons, and more which cause the subject to develop excruciating pain in their joints. After seeing how negatively HO affects a patient’s life, there is a clear need for prevention of the lesions to help improve the life of someone with HO. The host lab previously found that genetic or pharmacologic suppression of TGF-beta activated kinase 1 (TAK1) is efficient to mitigate HO. A next logical step of the study regarding HO is that the lowest possible dose of a TAK1 inhibitor, Takinib, with co-treatment of an anti-inflammatory drug, rapamycin, will suppress the growth of heterotopic ossification in mice. After induction of HO in our genetic mouse model for HO, a suboptimal dose of Takinib was orally administered with a range of rapamycin. Tissues with resulted HO were scanned by the micro-CT 500 microscopy scanner. CT scans of experimental mice with HO were investigated using a software called ITK Snap, which helps find the volume of the HO throughout the mice. The volumetric measurements revealed that combinations of suboptimal doses of Takinib and rapamycin effectively suppressed the growth of HO, or bone growth in soft tissues. Our findings suggest that co-treatment of TAK1 inhibitors with anti-inflammatory drugs, such as rapamycin, is the way to suppress the growth of heterotopic ossification with minimal side effects of each chemical. The study hopes to identify the lowest dose of the main anti-inflammatory chemical and how this dose will be effective in reducing the growth of HO. The identified chemical dose will ultimately serve as an efficient treatment for HO without adverse reactions not only in mice, but also in humans.

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Midfacial Defects with Ectopic Cartilages through Ectopic X Chromosome Inactivation by Enhanced Bone Morphogenic Protein Signaling

djandary

Craniofacial defects have affected some humans from birth, running rampant without many methods to lessen the impact. We aim to explore potential solutions to the phenomenon using model mice. We recently reported that transgenic mice with enhanced bone morphogenic protein (BMP) signaling in neural crest cells induced midfacial defects along with ectopic cartilages in the face but not in trunk neural crest cells (NCCs). Here, we hypothesized that enhanced BMP signaling in NCCs formed ectopic cartilages, resulting in midfacial defects. Single-cell RNA sequencing identified candidate genes that may be involved in the ectopic cartilage formation. Among them, Xist, a central component of X chromosome inactivation, is our focus because it was significantly increased in cranial NCCs from mutant mice but not in trunk NCCs from mutant mice. That led us to the idea that ectopic X chromosome inactivation by increased Xist is responsible for the ectopic cartilages in the face since Xist is not increased in trunk NCCs, and ectopic cartilages did not form in the trunk. To analyze that, we counted inactivated X chromosomes of cranial and trunk NCCs, allowing us to analyze how they impacted ectopic cartilage formation. Female cells normally inactivate one of two X chromosomes in a nucleus. Here, we showed that some of the cranial NCCs from mutant mice have two inactivated X chromosomes in a nucleus, which means ectopic X chromosome inactivation. Moreover, trunk NCCs from both control and mutant mice did not have two inactivated X chromosomes in a nucleus as we expected. Our preliminary results indicated that cranial NCCs from mutant mice have ectopic X chromosome inactivation, and trunk NCCs from mutant mice did not have ectopic X chromosome inactivation. That outcome supports that ectopic X chromosome inactivation in the cranial region is partially responsible for ectopic cartilage formation. That area could be a target for clinical treatment of the ailment. Considering the increased Xist in mutant mice, an inhibitor would be ideal for treatment, allowing X chromosome inactivation.

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Effects of temporomandibular joint disorder in chewing cycle

yokawase

Temporomandibular joint disorders (TMJD) are a series of disorders that affect the joint articulating the mandible and the skull, which is responsible for jaw movement. Abnormal jaw movement and abnormal temporomandibular joint (TMJ) shape are typical symptoms in TMJD patients. It is yet unknown whether abnormal TMJ movement is a result of the alterations in the TMJ in TMJD. In this study, we will use Evc2 mutant mice, which bears TMJ in abnormal shape, to understand if abnormal joint shape may lead to abnormal jaw movement. Currently, video of one mutant mouse, which has its Evc2 gene deleted in neural crest derived tissues, and one control mouse were taken to analyze jaw movement. After tracking fiducial markers planted in the mice with a program called XMALab onto a 3D coordinate plane for four consistent chews, we discovered a difference in chewing pattern between the mutant mouse and the control mouse by looking at the distance between the mandible and the skull in the duration of its chewing. We found that while the control mouse clearly had two types of chewing patterns, the mutant mouse only had a scattered chewing pattern with one noticeable type of chewing pattern. The chewing range of the mutant mouse was approximately half of that of the chewing range of the control mouse. Possible explanations of this is that the mutant mouse possibly is not physically capable of moving the jaw to do two cycles or the mouse could be in possible pain, preventing the two chewing patterns we saw in control. There is a notable difference in the chewing patterns between the control mouse and the mutant mouse, indicating that abnormal TMJ impacts chewing cycle.

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Development of PROTAC-based degrader of ERG transcription factor in prostate cancer

vizeng

Victoria Zeng Pronouns: she/her/hers Research Mentor(s): Xiaoju Wang, Associate Research Scientist Research Mentor School/College/Department: Pathology-Michigan Center for Translational Pathology, Michigan Medicine Presentation Date: Thursday, April 22, 2021 Session: Session 3 (1pm-1:50pm) Breakout Room: Room 11 Presenter: 5 Event Link Abstract For privacy concerns this abstract cannot be published at this time. Authors: Xiaoju Wang, Victoria

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Use of Novel Small-Molecule PP2A Activators in Prostate Cancer Cell Lines

mgiambi

Dysregulation of kinases and phosphatases in the signal-transduction-pathway disrupts cellular homeostasis and can result in serious diseases and a variety of cancers. The dysregulation of phosphatases in cancer have received little attention by the scientific community and thus additional knowledge of their role in carcinogenesis is needed to better understand cancer progression and to explore their potential as drug targets (Leonard, 2020). Specifically, I have been helping two staff scientists in the Narla lab study the post-translational modifications of protein-phosphatase PP2A in prostate cancer using molecular biology assays and to test novel small-molecule PP2A activators the Narla lab is developing. These novel small-molecule PP2A activators are expected to prompt downregulation of oncogenic transcription factors and modulate post-translational changes.

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Identification of novel genetic drivers of pediatric tumors

nraskind

Cancer-causing processes such as smoking and exposure to UV-light leave behind unique mutational signatures among the DNA of cancer patients. The analysis of mutational signatures in raw tumor data to produce/solidify a diagnosis would greatly benefit cancer patients and help streamline their prognosis. My project deals with the analysis of variant data obtained from tumor samples in order to determine which mutational signatures are present, utilizing technologies such as deconstructSigs, siglasso, and quadratic programming, as well as the well-established COSMIC mutational signatures.

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