Browsing by Author "Kimble-Hill, Ann C."

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    Best Practices to Diversify Chemistry Faculty
    (ACS, 2022-01) Agan, Marie Little Fawn; Joseph, Reni; Rivera-Figueroa, Armando; Chan, Benny C.; O’Connor, Abby R.; Ondrechen, Mary Jo; Jones, Wayne E.; Dorhout, Peter K.; Kimble-Hill, Ann C.; Biochemistry and Molecular Biology, School of Medicine
    Many academic institutions have looked at various ways to make their faculty a more diverse and inclusive group of people that better reflect the demographic swath of their current and future student bodies. This is even more so important in chemistry departments, where there has long been a discussion on the “leaky pipeline” for women and underrepresented groups. The work presented here examines programs and policies at various departments aimed at increasing the diversity of their faculty applicant pool, and compares them against the reception of the general scientific community by way of applicant demographics and the use of a survey instrument designed to ascertain the advertisement language that lends to a more diverse applicant pool. The combination of these results is then used to generate a list of best practices that administrations and academic search committees can use to improve their ability to attract diverse talent.
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    Defining the Roles of Various Lysines and Arginines in Amot Lipid Binding
    (Office of the Vice Chancellor for Research, 2014-04-11) Hall, L'eCelia; Kimble-Hill, Ann C.; Wells, Clark D.; Hurley, Thomas
    One of the defining traits of cancerous cells is proliferation. The focus of this study is on the proliferation of mammary cells. As an adaptor protein, the Amot membrane binding event is key to the localization and sorting of proteins responsible for cellular differentiation, proliferation, and migration. The Amot coiled-coil homology domain (ACCH) is a lipid-binding domain responsible for cholesterol affinity and binding to endothelial membranes. Our working hypothesis is that the ability to modulate Amot lipid-binding will lead to means to prevent ductal cell hyperplasia progression into breast cancer tumors. We will determine which residues are responsible for lipid-binding by changing positively charged lysine and arginine into uncharged or negatively charged amino acids. Approximately 40 of these mutations have been screened using a liposome binding assay which mimics how the protein binds with the cell membrane by using an in vitro mixture of lipids similar to that seen in endothelial cells. Forster resonance energy transfer (FRET) was used to confirm significant decreases in lipid binding of ACCH mutants selected from the liposome binding assay, as energy transfer only occurs when the tyrosines in the protein and the Dansylated liposome are in close proximity to each other. In order to saturate the binding affinity of the mutants, the liposomes will be combined with cholesterol in increasing amounts. It has been found that Amot protein is concentrated in areas of PI with higher levels of cholesterol. This will provide a target for the ACCH domain to associate with in the membrane. Mutants deemed important from this study will then be transformed into human cells to study their effects on cell polarity, signal transduction, cell shape, and cellular proliferation.
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    Development of Selective Inhibitors for Aldehyde Dehydrogenases Based on Substituted Indole-2,3-diones
    (American Chemical Society, 2014-02-13) Kimble-Hill, Ann C.; Parajuli, Bibek; Chen, Che-Hong; Mochly-Rosen, Daria; Hurley, Thomas D.; Department of Biochemistry & Molecular Biology, IU School of Medicine
    Aldehyde dehydrogenases (ALDH) participate in multiple metabolic pathways and have been indicated to play a role in several cancerous disease states. Our laboratory is interested in developing novel and selective ALDH inhibitors. We looked to further work recently published by developing a class of isoenzyme-selective inhibitors using similar indole-2,3-diones that exhibit differential inhibition of ALDH1A1, ALDH2, and ALDH3A1. Kinetic and X-ray crystallography data suggest that these inhibitors are competitive against aldehyde binding, forming direct interactions with active-site cysteine residues. The selectivity is precise in that these compounds appear to interact directly with the catalytic nucleophile, Cys243, in ALDH3A1 but not in ALDH2. In ALDH2, the 3-keto group is surrounded by the adjacent Cys301/303. Surprisingly, the orientation of the interaction changes depending on the nature of the substitutions on the basic indole ring structure and correlates well with the observed structure–activity relationships for each ALDH isoenzyme.
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    Discovery of Novel Regulators of Aldehyde Dehydrogenase Isoenzymes
    (2011-05) Parajuli, Bibek; Kimble-Hill, Ann C.; Khanna, May; Ivanova, Yvelina; Meroueh, Samy; Hurley, Thomas D
    Over the past three years we have been involved in high-throughput screening in an effort to discover novel small molecular modulators of aldehyde dehydrogenase (ALDH) activity. In particular, we have been interested in both the activation and inhibition of the three commonly studied isoenzymes, ALDH1A1, ALDH2 and ALDH3A1, as their distinct, yet overlapping substrate specificities, present a particularly difficult challenge for inhibitor discovery and design. Activation of ALDH2 has been shown to benefit cardiovascular outcome following periods of ischemia and renewed interest in specific inhibition of ALDH2 has application for alcohol aversion therapy, and more recently, in cocaine addiction. In contrast, inhibition of either ALDH1A1 or ALDH3A1 has application in cancer treatments where the isoenzymes are commonly over-expressed and serve as markers for cancer stem cells. We are taking two distinct approaches for these screens: in vitro enzyme activity screens using chemical libraries and virtual computational screens using the structures of the target enzymes as filters for identifying potential inhibitors, followed by in vitro testing of their ability to inhibit their intended targets. We have identified selective inhibitors of each of these three isoenzymes with inhibition constants in the high nanomolar to low micromolar range from these screening procedures. Together, these inhibitors provide proof for concept that selective inhibition of these broad specificity general detoxication enzymes through small molecule discovery and design is possible.
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    Identification of Specific Lysines and Arginines That Mediate Angiomotin Membrane Association
    (American Chemical Society, 2019-04-30) Hall, Le’Celia; Donovan, Emily; Araya, Michael; Idowa, Eniola; Jiminez-Segovia, Ilse; Folck, Anthony; Wells, Clark D.; Kimble-Hill, Ann C.; Biochemistry and Molecular Biology, School of Medicine
    The family of Angiomotin (Amot) proteins regulate several biological pathways associated with cellular differentiation, proliferation, and migration. These adaptor proteins target proteins to the apical membrane, actin fibers, or the nucleus. A major function of the Amot coiled-coil homology (ACCH) domain is to initiate protein interactions with the cellular membrane, particularly those containing phosphatidylinositol lipids. The work presented in this article uses several ACCH domain lysine/arginine mutants to probe the relative importance of individual residues for lipid binding. This identified four lysine and three arginine residues that mediate full lipid binding. Based on these findings, three of these residues were mutated to glutamates in the Angiomotin 80 kDa splice form and were incorporated into human mammary cell lines. Results show that mutating three of these residues in the context of full-length Angiomotin reduced the residence of the protein at the apical membrane. These findings provide new insight into how the ACCH domain mediates lipid binding to enable Amot proteins to control epithelial cell growth.
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    Incorporating Identity Safety into the Laboratory Safety Culture
    (American Chemical Society, 2021-03-22) Kimble-Hill, Ann C.; Biochemistry and Molecular Biology, School of Medicine
    Chemistry practitioners, particularly in educational settings, often associate building strong safety cultures with compliance or regulatory requirements around laboratory glass-ware, equipment, flammable and incompatible materials, signage, container labels, and safety data sheets. Other fields of science also emphasize biohazardous materials, animal handling, human subject, and ergonomics. However, little attention in the literature has gone toward describing the interpersonal interactions and behaviors affecting the physical and emotional safety and wellbeing of laboratory trainees and personnel from marginalized backgrounds. This work unifies known approaches of building strong safety cultures and principles for preventing identity cues that threaten safety within a laboratory environment. Specifically, this work uses the four principles of chemical safety RAMP model as a conceptual framework for integrating identity safety within the laboratory safety culture.
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    Insights Gained into Marginalized Students Access Challenges During the COVID-19 Academic Response
    (ACS Publications, 2020-08-17) Kimble-Hill, Ann C.; Rivera-Figueroa, Armando; Chan, Benny C.; Lawal, Wasiu A.; Gonzalez, Sheryl; Adams, Michael R.; Heard, George L.; Gazley, J. Lynn; Fiore-Walker, Benjamin; Biochemistry and Molecular Biology, School of Medicine
    The American Chemical Society (ACS) Committee on Minority Affairs (CMA) endeavors to support all chemistry faculty and staff as they educate all of our students during this pandemic. While the chemistry education community and the ACS have both provided resources as most institutions transitioned to virtual platforms, this pandemic disproportionally affects our students of color, lower socio-economic and rural backgrounds, and students with disabilities. Specifically, these students must overcome hurdles of technology access, environmental disruptions, and cultural pressures in order to be successful. Therefore, CMA has formulated partnerships with both academic and industrial institutions to highlight some best practices to improve future virtual learning experiences of these oftentimes marginalized students. Specifically, the work presented here examines programs and policies at three academic institutions with very different student body demographics and surrounding learning environments (Indiana University Purdue University Indianapolis (IUPUI), The College of New Jersey (TCNJ), and Los Angeles Community College District (LACCD)) with an attempt to identify variables that enhance marginalized student success in chemistry courses. The combination of their results suggests elements such as access to technology, home responsibility, and impostor syndrome, that other learning programs should consider to increase virtual learning success. Furthermore, other stopgap measures implemented at industrial partners give insight as to how these considerations can be implemented during virtual internship programs to meet their learning objectives associated with entering their institutional pipeline.
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    Insights Gained into the Use of Individual Development Plans as a Framework for Mentoring NIH Postbaccalaureate Research Education Program (PREP) Trainees
    (American Chemical Society, 2022) Hardy, Tabitha M.; Hansen, Michele J.; Bahamonde, Rafael E.; Kimble-Hill, Ann C.; Biology, School of Science
    This study examines the use of individual development plans (IDPs) in a structured mentoring program as an effective mechanism for reducing identity-related anxiety for underrepresented trainees and increasing their learner agency. Social cognitive theory served to provide the theoretical framework for our implementation of IDPs and our investigation of the effects of completing IDPs on trainees attaining academic goals and subsequent success in enrolling in competitive PhD programs. Results suggest that IDPs are also an effective tool that can allow faculty mentors to provide the social support necessary for trainees to persist in accomplishing their short- and long-term learning goals. Additionally, trainee self-agency, in the use of the IDP and mentoring, seemed to provide an alternative narrative to ability as a sole predictor of STEM achievement. We also found that IDPs helped foster social support networks, providing stability, predictability, and a sense of belonging. Specifically, IDPs helped foster the emotional and informational support necessary for trainees to persist, despite obstacles, as they strived to attain their learning goals.
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    A Model for Crafting Diversity, Inclusion, Respect, and Equity (DIRE) Policy Statements Toward Catalyzing Organizational Change
    (American Chemical Society, 2021-03-24) Gentle-Genitty, Carolyn; Merritt, Breanca; Kimble-Hill, Ann C.; School of Social Work
    We present a model for STEM organizations to write catalytic diversity, inclusion, respect, and equity (DIRE) policy statements as structured steps for sustained action.
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    Pervasiveness and Impact of Single-Day Episodes of Harassment, Microaggression, and Incivility of Biomedical Health Trainees
    (Department of Psychology, Indiana University-Purdue University Indianapolis, 2023-07-01) Stockdale, Margaret S.; Kimble-Hill, Ann C.; Dinh, Tuyen K.; Mosier, Amanda E.; Washington, Darius; Wu, Wei; Roper, Randall
    The biomedical workforce needs the talents and insights of people from all cross-sections of identity to advance scientific discovery and to improve research application. To build and sustain this workforce, trainees must be treated with respect and support. We assessed the prevalence of daily experiences of harassment, racial mistreatment, and incivility by conducting a national survey of NIH funded graduate students (n=249) and post-doctoral fellows (n=148). Our findings suggest there is an alarming prevalence of mistreatment within research training environments. Our random sampling of F30, F31, F32, and K99 recipients suggests that as many as 45% of graduate students and postdoctoral trainees experience or observe at least one form of mistreatment on any given day, with incivility being the most reported experience. Furthermore, we found that mistreatment experiences and observations were significantly associated with negative program attitudes, indicating a potential risk for attrition among trainees. Moreover, the prevalence of mistreatment was consistent across gender and racial identities. These findings underscore the urgent need for interventions to address mistreatment in research training environments. This study is the first to report empirical data from the trainee perspective on the prevalence and impact of single-day mistreatment in biomedically relevant training programs. Our research is important for understanding the underpinnings of the mentor-mentee and peer-peer interactions responsible for the prevalence of negative environments, as well as highlighting where interventions are necessary to develop supportive leadership and lab culture practices that will improve career outcomes for participants in these fields.