MEDICA@MUSC (Medical University of South Carolina)
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Role of PRMT5 in ULK1-Mediated Autophagy and Breast Cancer Therapy
Get PDFPRMT5 (Protein arginine methyltransferase 5) is the predominant type II PRMT that monomethylates and symmetrically dimethylates arginine residues of histone and none- histone proteins to regulate diverse cellular processes. PRMT5 overexpression has been implicated in tumorigenesis and other diseases and has gained trac1on as a poten1al an1tumor target with some of its inhibitors being tested in clinical trials. Despite the well- established an1tumor effect of PRMT5 inhibitors, how the efficacy of these inhibitors is regulated is unexplored. We show in this study that autophagy blockage enhances cellular sensi1vity to PRMT5 inhibitor in triple nega1ve breast cancer cells. Both gene1c deple1on and pharmacological inhibi1on of PRMT5 evoke cytoprotec1ve autophagy. We further establish that PRMT5 suppresses basal autophagy across different breast cancer types. Mechanis1cally, PRMT5 catalyzes monomethyla1on of ULK1 at R532 to suppress its autophagic func1ons. As a result, ULK1 inhibi1on or dele1on blocks PRMT5 deficiency- induced autophagy and sensi1zes cells to PRMT5 inhibitor. Our study iden1fies inducible autophagy as an important determinant of cellular sensi1vity to PRMT5 inhibitor, and also establishes ULK1 as a bonafide substrate of PRMT5 in the autophagy, providing a ra1onale for combining PRMT5 and autophagy inhibitors in cancer therapy
Stronger Together: Collaborating on Collection Development with Subject Niche Liaisons Librarians
No full textObjectives: A strong collection in a subject niche that supports the research and educational needs of your users can be complicated. Whether you are the liaison librarian or just working with the subject, it is important to know the current collection so that you can anticipate the needs of your users. In 2017, after doing an initial broad collections assessment, the Director of Information Resources and Collections Services (DIRCS) identified subject areas for additional development. The objective was to see how collaborating with liaison librarians during the collection development process affected the resources within the areas of pharmacy and dental medicine. Methods: A weighted binary classification grid was created which identified the core electronic collection first for pharmacy, then later for dental medicine. Utilizing a collaborative approach, the Director of Information Resources and Collections Services partnered with the liaison librarians for pharmacy and dental medicine. Information was shared about potential resources requested by faculty to complement the core collection. Librarians conducted a search of the collection development literature in several databases (PubMed, Academic Search Complete, CINAHL, PsychInfo) to find articles describing best practices for niche areas. Citations were collected using EndNote and uploaded into Covidence for screening. COUNTER usage statistics of pharmacy and dental medicine resources were collected and analyzed. Additionally, Cost Per Use (CPU) data for both collections is being analyzed. Results: Results are forthcoming based on completion of data analysis. Conclusions: Preliminary data analysis indicates that collaborating with liaison librarians for resources that were identified as Core Collections within pharmacy and dental medicine subjects has initially shown a better Cost Per Use (CPU) than when compared with resources that were identified and obtained, but not promoted through collaboration.https://medica-musc.researchcommons.org/posters/1032/thumbnail.jp
Pitx2 Influences Cardiomyocyte Ferroptosis and Fibrotic Scarring in the Regenerative and Non-Regenerative Mouse Heart after Myocardial Infarction
No full textEvery 40 seconds, someone in the United States has a myocardial infarction (MI), or heart attack. Following MI, mature mammalian cardiomyocytes (CMs) are unable to repopulate the injured myocardium due to a low turnover rate of 0.5-2% per year. The lack of CM renewal and cardiac regeneration requires infiltration of cardiac fibroblasts (CFs) to deposit ECM preventing cardiac rupture and maintaining tissue integrity. The infiltration and increased ECM deposition result in a fibrotic scar that lacks contractility and leaves the heart with decreased function. However, the neonatal mammalian heart retains a regenerative capacity during the first week of life. Understanding the mechanisms that underlie cardiac regeneration is imperative to developing therapeutic techniques and treatments for patients who experience MI.
Recent work by our lab has identified developmental transcription factor Pitx2 as a regulator of Gpx4, a selenoprotein essential to ferroptosis resistance. In this study, we attempted to determine the extent of ferroptosis after MI. Regenerative postnatal day 1 (P1) and non-regenerative postnatal day 7 (P7) mice were subjected to permanent left anterior descending artery occlusion surgery (LAD-O) and hearts were collected at multiple timepoints to profile scar progression and cell death. Three forms of cell death including ferroptosis were profiled using confocal microscopy. To determine if Pitx2 expression affected ferroptosis relevant genes, RNA sequencing was done on human induced pluripotent stem cells differentiated into cardiomyocytes (iCMs) as well as in Pitx2 CM conditional knockout (Pitx2-cKO) and overexpression (Pitx2-OE) mice.
Our work also identified Pitx2 as a regulator of Tsp1, an activator of latent TGF-β, a potent fibrotic factor. To examine if Pitx2 expression could alter fibroblast activation and fibrotic scar formation, western blot analysis of Pitx2cKO and Pitx2OE was performed. We found that Pitx2 expression was negatively correlated with Tsp1 expression. Further, we investigated if ferroptosis affected CFs and found CFs exhibit greater resistance to ferroptosis than CMs in a density-dependent manner. We confirmed that at mid to high density, CFs express greater amounts of anti-ferroptotic iron storage proteins, the ferritins. We then explored the relationship between CFs and CMs during ferroptosis. Using a Rosa26-eGFP-DTA reporter under a periostin (Postn) promoter, PostnMCM/+;Rosa26eGFP-DTA, we ablated activated fibroblasts from the mouse heart and saw increased lipid peroxidation, a hallmark of ferroptosis. To elucidate the mechanism of protection by CFs, we co-cultured human cardiac fibroblasts (HCFs) with iCMs and observed that the cell types share iron burden after iron overload.
This project has led to new understanding of the mechanisms of CM loss after MI as well as to the role of CFs in protecting CMs from cellular death and in scar formation in the regenerative and non-regenerative heart
Resiliency Strategies for Brightly Burning Librarians
Get PDFPurpose: Librarianship is a helping profession which means caring is one of our superpowers, yet also makes us more likely to cross our own boundaries in our efforts to support our users, leaving us vulnerable to burnout. Our best intentions, fears of missing out, and need to prove our value often drive us to the limits of our abilities to sustain the levels of service we provide. This presentation will prepare librarians with strategies to promote overall well-being and foster resiliency.
Description: Health sciences librarians often happily agree to new, exciting opportunities, only to find that our best intentions end up not being sustainable. Fortunately, it is possible to keep your sanity and remain a shining star in the eyes of your users. This presentation will bust myths like the “work-life balance” and provide alternatives to the “just say no” mantra of self-preservation. We will offer practical strategies for setting boundaries, practicing self-care, and seeking out a support network as healthy strategies to reduce the risk of librarian burnout.
Outcome/Discussion: This session will present strategies to promote health science librarians’ overall well-being and encourage the use of resiliency strategies to achieve professional goals. Finding sustainable work-life harmony is possible, and it is essential to find a customized approach that works best for your situation and specific competing priorities
Librarian Advocates for Open Educational Resources (OER) as a Catalyst for Innovation in Health Sciences Education
Get PDFPurpose: Data shows that at least 81% of medical students and 75% of health professional doctoral students graduate and enter the profession with student loans. Access to textbooks and ancillary instructional materials is essential, yet data shows that textbook prices have increased over 1000% between 1977-2015, exacerbating the systematic barriers to student access, affordability, and success in higher education. Open Educational Resources (OER) can reduce student textbook costs while also giving faculty the flexibility to adapt course materials to meet specific course needs. Librarians have experience leveraging subscription resources to reduce student costs and are well positioned to promote the adoption of OER in higher education and support campus affordability initiatives.
Description: This interactive session will empower librarians to take the first step towards implementing affordable learning initiatives at their own institutions by providing an overview of OER, highlighting resources for identifying high-quality OER in the health science disciplines, and discussing techniques to engage faculty, students, and administrators as advocates for adopting OER and library-subscribed resources on your campus.
Outcome/Discussion: Librarians are a natural fit to lead textbook affordability initiatives in the current climate of concern over student debt, especially when institutions are actively investigating student cost saving measures. We have an opportunity to work with the decision-makers to offset some of that financial burden by using zero or low-cost textbooks and ancillary materials. Examples will be shared so presentation attendees will leave the session with ideas to approach implementing OER initiatives at their institutions
Exploring the Unmet Care Needs of Women with Chronic Obstructive Pulmonary Disease (COPD)
Get PDFThe primary objective of this study was to examine the feasibility of study procedures to and explore the unmet needs and potential barriers of women with advanced COPD who may need palliative care (PC). This multi-method study was guided by the adapted Hierarchy of Needs Model and explored unmet care needs, assessed knowledge of PC services, and identified barriers that women experience when receiving or during the implementation of PC. Further exploration of PC needs by sex provided information on unmet care needs of women with advanced COPD. Participants were recruited through convenience sampling by using COPD Patient-Powered Research Network (COPD PPRN), part of the COPD Foundation, and social media. Surveys were administered to women with COPD for self-report of symptoms, quality of life, unmet needs, patient outcomes, resources, and barriers to receiving care. Snowball sampling was utilized to identity participants to complete semi-structured interviews to explore the unmet care needs of women with advanced COPD. Feasibility was determined by eligibility criteria, study procedures, and data collection methods.
To our knowledge, this is one of the first studies to explore the unmet care needs of women with advanced COPD. This study will address a gap in the literature regarding care needs of women with COPD and will provide preliminary insight into knowledge levels of COPD and PC, and finally, identify barriers to care in this population. Study procedures were feasible as determined by the ability for women to complete surveys and interviews without an additional burden, recruitment completed within the defined 6-month timeframe, and high participation rates in surveys if eligible
