Cutaneous Lupus Erythematosus (CLE) is an autoimmune disorder marked by scarring skin lesions, often triggered by exposure to ultraviolet (UV) light resulting in a significant loss of quality of life for CLE patients. Better understanding of the molecular mechanisms driving CLE is needed as currently, the lack of Food and Drug Administration (FDA)-approved therapies for CLE presents a fundamental challenge in the treatment of CLE patients. The outermost layer of the skin is known as the epidermis, which consists of mostly keratinocytes. Interferon kappa (IFN-?), a member of the type I IFN family, is constitutively expressed in keratinocytes. IFNK overexpression in lesional lupus skin predisposes CLE patients to inflammation and photosensitivity, thus it is an intriguing target for novel therapeutics. Previously, we had observed a significant delay in IFNK expression relative to IFN-ß, another member of the type I IFN family, following stimulation with poly-IC, an activator of the antiviral TLR3 signaling pathway, or UVB. In addition, upregulation of IFNK was dependent on STING, an endoplasmic reticulum adaptor protein. We thus sought to further understand the regulation of different IFNs in keratinocytes. Using CRISPR-Cas9, we generated knockout keratinocytes for IFNB expression. Here, we reveal that in the absence of IFN-ß, IFNK expression is significantly reduced in keratinocytes treated with poly-IC or UVB. Elimination of mediators downstream of the type I IFN receptor, such as STAT1, also abrogated IFNK but not IFNB expression. Further, IFNK, but not IFNB, expression remained dependent on STING signaling upon UVB-irradiation. Given this information, therefore, we suggest that early triggering of IFNB is required to drive a STING-mediated upregulation of IFNK. Currently, we are examining whether this regulation is aberrant in CLE vs. healthy control keratinocytes, which would provide a mechanism for dysfunctional overexpression of IFNK in CLE skin. If so, this pathway would serve as a target for reducing inflammation and photosensitivity in CLE patients.
UROP Fellowship: Research Scholars
Herbig stars of spectral type Ae/Be are young stars of 1.5-10 solar masses. Current models of young stars’ temperatures and radii as a function of mass are not well calibrated. In binary star systems, a transit, or a periodic dip in apparent brightness of the star, occurs when the one star passes in front of the other star, blocking some of the light of the primary star, creating an eclipse effect. These eclipsing binary star systems allow us to obtain estimates for parameters of the orbiting objects such as the masses, radii, orbital period, orbital inclination, semi-major axis, et cetera. Obtaining these parameters for these young stars will allow for better calibration for models of young stars’ properties. In general, researching stars unlike our sun is important because it gives the context that our solar system exists in and gives us a broader understanding of the universe. We reduced, analyzed, and modeled the Herbigs’ light curves, which are plots of flux versus time, from the NASA TESS mission. We identified and examined the light curves of stars that showed evidence of orbiting companions using Python packages such as Batman, Eleanor, and Phoebe. Using these packages we were able to create and fit model light curves to the data and obtain estimates of parameters for our stars of interest.
Fungal pathogens like Candida albicans can cause devastating human disease. Treatment of candidemia is complicated by the high rate of resistance to common antifungal therapies and the toxicity of many antifungal compounds due to the conservation between essential mammalian and fungal proteins. As the number of immunocompromised and hospitalized patients vulnerable to fungal infections increases, it is essential to discover new targets and approaches for targeting these deadly fungal pathogens. An attractive new approach for antimicrobial development is to target virulence factors; these are non-essential processes that are required for the organism to cause disease in human hosts. This approach expands the potential target space while reducing the selective pressure towards resistance, as these targets are not essential for viability. In C. albicans, the key virulence factor is a morphogenetic switch from yeast to filaments. We have developed a high-throughput image analysis pipeline that can readily distinguish between yeast and filamentous growth in C. albicans and identify cytotoxic molecules. Based on this clear phenotypic assay, we have screened compounds for their ability to inhibit this important virulence factor or cause fungistatic or fungicidal effects. Also, to avoid host cell toxicity, the compounds screened are compounds used as treatments for other medicinal purposes. We have begun to use these compounds to screen for resistant mutants of C. albicans, and in the future we will use these resistant mutants to leverage the tractable genetic systems of C. albicans to determine mechanism of action, thus allowing for targeted development of new antifungal therapies. Overall, this approach will build a platform for rapidly developing new molecules for antifungal therapeutics.
Conversations about mental health and masculinity and subsequent support in these realms is disproportionately low among Black males ages 18 to 30, and notably so at predominantly white, tertiary education institutions. Developed in 2008 by Dr. Daphne C. Watkins at the University of Michigan’s School of Social Work, The Young Black Men, Masculinities, and Mental Health (YBMen) Project was founded as an online social support and health education research initiative. Seeking to provide a safe space for young Black collegiate men to discuss mental health and identity concerns, the online format was shaped to decrease barriers to honest discussion. Given the historical reluctance of Black men ages 18-30 to discuss mental well-being and masculinity related issues in face to face settings, The YBMen Project in its current form mindfully considers the cultural sensitivity and gender norms influencing this trend to create a virtual space more suited to their needs. Targeting Black men in preclinical stages of mental health distress, the project focuses on attending to young Black men with a desire to express emotional and psychological needs within a cultural milieu that has not previously proven conducive to this process. Beginning its first phase in 2013, the YBMen Project has spread to multiple midwest college campuses to both implement and test the efficacy of the program in addressing a hegemonic view of Black masculinity and its related mental health issues. In the context of the previous work done on other campuses, this sub-study examines the feasibility of effecting the YBMen Project on the University of Michigan Ann Arbor campus and discusses the impact of Covid-19’s virtual world on the availability of resources for Black males at UM and perceptions of receptivity to an online e-health intervention. This research will address the willingness, needs, and methods best suited for the mental health and social support needs of Black men at the University of Michigan (UM) with respect to the intersectionality of their culture and identity.
ATLAS is one of the four major experiments at the Large Hadron Collider (LHC) at CERN. It ia general-purpose particle physics experiment run by physicists from all around the world. ATLAS physicists test the predictions of the Standard Model, which encapsulates our current understanding of what the building blocks of matter are and how they interact. These studies can lead to ground-breaking discoveries, such as that of the Higgs boson, physics beyond the Standard Model, and the development of new theories to better describe our universe. ATLAS is made up of many different instruments and subsystems, and this research focuses specifically on the Muon Spectrometer. Specifically within the Muon Spectrometer, this research analyzes data from Monitored Drift Tubes (MDTs). In short, muons are one of the very few things that get through the first three detectors within ATLAS, and MDTs work to trace the curved path of the muon as it passes through, which then allows for the calculation of its momentum. MDTs are filled with gas, and as the muon passes through a number of tubes, it leaves a trail of charged electrons that drift to the center of each tube. Recording the time of this drift process is what leads to the tracing the muon’s path. The goal of this research is to understand the issues that may develop in these drift tubes while everything is running and data is being taken. An example of this is a Single Event Upset (SEU). SEUs occur when a large energy deposition from one of the charged particles disrupts the functioning of the electronics, specifically, a state change of a logical element (a memory bit). The study will produce and compare a large variety of histograms from the beginning and ends of runs, and checking for any discrepancies. The research will look at different types of issues and their frequencies in 2018 proton-proton collision data.
Our research looked into institutional responses to substance-using pregnant women. Institutions include entities such as the criminal justice system, the medical system, the legal system, and the child welfare system. Data gathered from state laws and statutes, newspapers, court cases, medical guidelines, and more were examined to put together a picture of how different United States entities worked together and separately in cases of substance-using pregnant women. Historical responses, such as those used during the 1980’s “crack epidemic”, as well as modern responses, such as those being used during the “Opioid epidemic”, were examined.
On the surface, the CPS (Chicago Public Schools) selective enrollment system seems to provide students with many opportunities and offers students access to a quality education at a high-performing school. Recently, however, both students and teachers have been speaking up about discrimination at these schools. This study will evaluate the different types of discrimination that students experience within the top five selective enrollment schools and discuss possible solutions to ending discrimination. This study specifically examines the question: What are the impacts of selective enrollment school practices on educational equity in urban school systems, particularly in Chicago Public Schools? A qualitative mixed methods study was used to analyze the student experience at these schools. We collected data from instagram posts from BIPOC Instagram pages from four of the five schools that were studied. Teacher interviews and local school council meetings were also used to gather information on the student experience at these schools. From these sources we found that racism and other forms of discrimination from teachers and staff members often can make students feel as if they are not wanted or do not belong at their high school. In addition to the issue of white supremacy, students also report that these selective schools often don’t consider other struggles that their students face when it comes to socioeconomic struggles. Many students also felt like their schools did not support them when they faced sexual harassment in these schools. All of these types of discrimination lead to a culture of discrimination where students feel like their concerns are being ignored by the school. This paper also looked into possible solutions for these issues of discrimination which included anti-racist staff training, minority teacher recruitment/retention, listening to student input, anti-racist curriculum and creating an anti-racist culture at schools.
This project looks in depth at the work of early filmmaker Georges Méliès who was a pioneer of special effects and story films during the late-nineteenth and early-twentieth centuries. Furthermore, we are looking to highlight the importance of Madeleine Malthête-Méliès, who had perhaps the longest active career of any film historian and whose main concentration was documenting her grandfather Georges Méliès, including locating his many lost films. Our focus has been supporting the publication of a translation of a key historical source that has long been unavailable in English, the late Madeleine Malthête-Méliès’ biography, Georges Méliès, L’Enchanteur, which is under contract with the University of Michigan Press. This book will make Méliès’ work better known to a wider audience including readers of English. We have worked to document the author’s work by arranging English subtitling of a video interview with Madeleine Malthête-Méliès, and have compiled a complete bibliography of the research publication connected with the organization she founded, Les Amis de Georges Méliès. We are summarizing relevant articles for discussion in the introduction to the biography and assisting in the publication of another book, Méliès Boots: Material Contexts for Early Film Manufacturing (University of Michigan Press, under contract). To further show how Georges Méliès has impacted the modern world, we are preparing a short film that will summarize research on Méliès at the University of Michigan undertaken since 2011 told from the point-of-view of a new generation of media makers who draw continuing inspiration from learning about Méliès and his work.
When teachers extend the purpose of an assignment beyond the walls of a classroom, students begin to care. Through an exploration of creative-writing pedagogy and the latest advancements in technology and publishing, this research aims to explore how to implement authentic audiences in secondary ELA and creative writing classrooms. Whether that be through letter-writing, community-based projects, or submitting work out to literary journals, the hope is that students will be able to confidently answer questions like “Who are we writing for?” and “Why does this matter?” To make the findings of this research more accessible to the intended audience of secondary teachers and students, this research will adopt and be delivered through one of the proposed forms of publication: the zine.
This project will investigate how filter bubbles — groups that are filled with people that share similar opinions that are isolated from others — form in social networks. Through simulated social networks with human participants, the spread of opinions and information are assessed as participants alter the structure of their social network by adding and removing neighbors. The participants’ decisions in altering their social network is made after participants view their neighbors’ responses in controversial issues. As a result, the impact of disagreement and differing opinions is analyzed. This study not only investigates the importance of a participant’s needs to surround themselves with like-minded people, but also explores how participants view their neighbors. The overall structure of the social network is examined between the rounds as groups begin to form in the social network. By studying these group formations, we hope to pinpoint the factors that further cause filter bubble formation.