Browsing by Author "O'Leary, Heather A."

Now showing 1 - 6 of 6
  • Thumbnail Image
    Item
    Cancer‐related knowledge, beliefs, and behaviors among Hispanic/Latino residents of Indiana
    (Wiley, 2023) Espinoza-Gutarra, Manuel R.; Rawl, Susan M.; Maupome, Gerardo; O'Leary, Heather A.; Valenzuela, Robin E.; Malloy, Caeli; Golzarri-Arroyo, Lilian; Parker, Erik; Haunert, Laura; Haggstrom, David A.
    Background: Cancer is the leading cause of death for Hispanics in the USA. Screening and prevention reduce cancer morbidity and mortality. Methods: This study administered a cross‐sectional web‐based survey to self‐identified Hispanic residents in the state of Indiana to assess their cancer‐related knowledge, beliefs, and behaviors, as well as to identify what factors might be associated with cancer screening and prevention. Chi‐square and Fisher's exact test were used to compare associations and logistic regression used to develop both univariate and multivariate regression models. Results: A total of 1520 surveys were completed, median age of respondents was 53, 52% identified as men, 50.9% completed the survey in Spanish, and 60.4% identified the USA as their country of birth. Most were not able to accurately identify ages to begin screening for breast, colorectal, or lung cancer, and there were significant differences in cancer knowledge by education level. US‐born individuals with higher income and education more often believed they were likely to develop cancer and worry about getting cancer. Sixty eight percent of respondents were up‐to‐date with colorectal, 44% with breast, and 61% with cervical cancer screening. Multivariate models showed that higher education, lack of fatalism, older age, lower household income, and unmarried status were associated with cervical cancer screening adherence. Conclusions: Among a Hispanic population in the state of Indiana, factors associated with cervical cancer screening adherence were similar to the general population, with the exceptions of income and marital status. Younger Hispanic individuals were more likely to be adherent with breast and colorectal cancer screening, and given the higher incidence of cancer among older individuals, these results should guide future research and targeted outreach.
  • Thumbnail Image
    Item
    Enhancing Hematopoietic Stem Cell Transplantation Efficacy by Mitigating Oxygen Shock
    (Elsevier, 2015-06-18) Mantel, Charlie R.; O'Leary, Heather A.; Chitteti, Brahmananda R.; Huang, XinXin; Cooper, Scott; Hangoc, Giao; Brustovetsky, Nickolay; Srour, Edward F.; Lee, Man-Ryul; Messina-Graham, Steve; Haas, David M.; Falah, Nadia; Kapur, Reuben; Pelus, Louis M.; Bardeesy, Nabeel; Fitamant, Julien; Ivan, Mircea; Kim, Kye-Seong; Broxmeyer, Hal E.; Department of Microbiology & Immunology, IU School of Medicine
    Hematopoietic stem cells (HSCs) reside in hypoxic niches within bone marrow and cord blood. Yet, essentially all HSC studies have been performed with cells isolated and processed in non-physiologic ambient air. By collecting and manipulating bone marrow and cord blood in native conditions of hypoxia, we demonstrate that brief exposure to ambient oxygen decreases recovery of long-term repopulating HSCs and increases progenitor cells, a phenomenon we term extraphysiologic oxygen shock/stress (EPHOSS). Thus, true numbers of HSCs in the bone marrow and cord blood are routinely underestimated. We linked ROS production and induction of the mitochondrial permeability transition pore (MPTP) via cyclophilin D and p53 as mechanisms of EPHOSS. The MPTP inhibitor cyclosporin A protects mouse bone marrow and human cord blood HSCs from EPHOSS during collection in air, resulting in increased recovery of transplantable HSCs. Mitigating EPHOSS during cell collection and processing by pharmacological means may be clinically advantageous for transplantation.
  • Thumbnail Image
    Item
    Implications of DPP4 modification of proteins that regulate stem/progenitor and more mature cell types
    (American Society of Hematology, 2013-07-11) Ou, Xuan; O'Leary, Heather A.; Broxmeyer, Hal E.; Microbiology & Immunology, IU School of Medicine
    Dipeptidylpeptidase (DPP) 4 has the potential to truncate proteins with a penultimate alanine, proline, or other selective amino acids at the N-terminus. DPP4 truncation of certain chemokines, colony-stimulating factors, and interleukins have recently been linked to regulation of hematopoietic stem/progenitor cells, more mature blood cells, and other cell types. We believe that the potential role of DPP4 in modification of many regulatory proteins, and their subsequent effects on numerous stem/progenitor and other cell-type functions has not been adequately appreciated. This review addresses the potential implications of the modifying effects of DPP4 on a large number of cytokines and other growth-regulating factors with either proven or putative DPP4 truncation sites on hematopoietic cells, and subsequent effects of DPP4-truncated proteins on multiple aspects of steady-state and stressed hematopoiesis, including stem/progenitor cell, and more mature cell, function.
  • Thumbnail Image
    Item
    The importance of hypoxia and extra physiologic oxygen shock/stress for collection and processing of stem and progenitor cells to understand true physiology/pathology of these cells ex vivo
    (Wolters Kluwer, 2015-07) Broxmeyer, Hal E.; O'Leary, Heather A.; Huang, Xinxin; Mantel, Charlie; Department of Microbiology and Immunology, IU School of Medicine
    PURPOSE OF REVIEW: Hematopoietic stem (HSCs) and progenitor (HPCs) cells reside in a hypoxic (lowered oxygen tension) environment, in vivo. We review literature on growth of HSCs and HPCs under hypoxic and normoxic (ambient air) conditions with a focus on our recent work demonstrating the detrimental effects of collecting and processing cells in ambient air through a phenomenon termed extra physiologic oxygen shock/stress (EPHOSS), and we describe means to counteract EPHOSS for enhanced collection of HSCs. RECENT FINDINGS: Collection and processing of bone marrow and cord blood cells in ambient air cause rapid differentiation and loss of HSCs, with increases in HPCs. This apparently irreversible EPHOSS phenomenon results from increased mitochondrial reactive oxygen species, mediated by a p53-cyclophilin D-mitochondrial permeability transition pore axis, and involves hypoxia inducing factor-1α and micro-RNA 210. EPHOSS can be mitigated by collecting and processing cells in lowered (3%) oxygen, or in ambient air in the presence of, cyclosporine A which effects the mitochondrial permeability transition pore, resulting in increased HSC collections. SUMMARY: Our recent findings may be advantageous for HSC collection for hematopoietic cell transplantation, and likely for enhanced collection of other stem cell types. EPHOSS should be considered when ex-vivo cell analysis is utilized for personalized medicine, as metabolism of cells and their response to targeted drug treatment ex vivo may not mimic what occurs in vivo.
  • Thumbnail Image
    Item
    Reframing Academic Productivity, Promotion and Tenure As a Result of the COVID-19 Pandemic
    (Magna, 2021-01-01) Sotto-Santiago, Sylk; Dilly, Christen K.; O'Leary, Heather A.; Craven, Hannah J.; Kara, Areeba; Brown, Cynthia; Kressel, Amy B.; Rohr-Kirchgraber, Theresa
    Faculty members have been impacted in a multitude of ways by the COVID-19 pandemic. In particular, faculty seeking promotion and tenure have been impacted by the disruption and inconsistent levels of productivity. In this article, we consider academic productivity in the context of clinical, research, education and service missions within higher education and the academic medicine professoriate. We offer a series of recommendations to faculty members, to institutions, and to professional societies in hopes we can challenge pre-existing deficits in promotion and tenure processes, and academic worth.
  • Thumbnail Image
    Item
    Utility of CRISPR/Cas9 systems in hematology research
    (Elsevier, 2017) Lucas, Daniel; O'Leary, Heather A.; Ebert, Benjamin L.; Cowan, Chad A.; Tremblay, Cedric S.; Department of Microbiology and Immunology, IU School of Medicine
    Since the end of the 20th century, the development of novel approaches have emerged to manipulate experimental models of hematological disorders, so they would more accurately mirror what is observed in the clinic. Despite these technological advances, the characterization of crucial genes for benign or malignant hematological disorders remains challenging, mainly because of the dynamic nature of the hematopoietic system and the genetic heterogeneity of these disorders. To overcome this limitation, genome editing technologies have been developed to specifically manipulate the genome via deletion, insertion or modification of targeted loci. These technologies have swiftly progressed, allowing their common use to investigate genetic function in experimental hematology. Amongst them, homologous recombination (HR)-mediated targeting technologies have facilitated the manipulation of specific loci by generating knockout and knock-in models. Despite promoting significant advances in the understanding of the molecular mechanisms involved in hematology, these inefficient, time-consuming and labor-intensive approaches did not permit the development of cellular or animal models recapitulating the complexity of hematological disorders. In October 2016, Dr. Ben Ebert and Dr. Chad Cowan shared their knowledge and experiences with the utilization of CRISPR for models of myeloid malignancy, disease, and novel therapeutics. Here we provide an overview of the topics they covered including insights into the novel applications of the technique as well as its strengths and limitations.