Chemistry & Biochemistry

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The Department of Chemistry and Biochemistry offers research-oriented programs culminating in the Doctor of Philosophy degree. The faculty in the department have expertise over a broad range of specialty areas including synthesis, structure, spectroscopy, and mechanism. In each of these fields, the strength of the department has been recognized at the international level.

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    Metabolomic Profiles and Pathways in Osteoarthritic Human Cartilage: A Comparative Analysis with Healthy Cartilage
    (MDPI AG, 2024-03) Wellhaven, Hope D.; Welfley, Avery H.; Brahmachary, Priyanka; Bergstrom, Annika R.; Houske, Eden; Glimm, Matthew; Bothner, Brian; Hahn, Alyssa K.; June, Ronald K.
    Osteoarthritis (OA) is a chronic joint disease with heterogenous metabolic pathology. To gain insight into OA-related metabolism, metabolite extracts from healthy (n = 11) and end-stage osteoarthritic cartilage (n = 35) were analyzed using liquid chromatography–mass spectrometry metabolomic profiling. Specific metabolites and metabolic pathways, including lipid and amino acid pathways, were differentially regulated in osteoarthritis-derived and healthy cartilage. The detected alterations in amino acids and lipids highlighted key differences in bioenergetic resources, matrix homeostasis, and mitochondrial alterations in OA-derived cartilage compared to healthy cartilage. Moreover, the metabolomic profiles of osteoarthritic cartilage separated into four distinct endotypes, highlighting the heterogenous nature of OA metabolism and the diverse landscape within the joint in patients. The results of this study demonstrate that human cartilage has distinct metabolomic profiles in healthy and end-stage OA patients. By taking a comprehensive approach to assess metabolic differences between healthy and osteoarthritic cartilage and within osteoarthritic cartilage alone, several metabolic pathways with distinct regulation patterns were detected. Additional investigation may lead to the identification of metabolites that may serve as valuable indicators of disease status or potential therapeutic targets.
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    Osteoarthritis Year in Review 2024: Molecular biomarkers of osteoarthritis
    (Elsevier BV, 2024-10) Welhaven, Hope D.; Welfley, Avery H.; June, Ronald K.
    Objective. To provide a comprehensive and insightful summary of studies on molecular biomarkers at the gene, protein, and metabolite levels across different sample types and joints affected by osteoarthritis (OA). Methods. A literature search using the PubMed database for publications on OA biomarkers published between April 1, 2023 and April 30, 2024 was performed. Publications were then screened, examined at length, and summarized in a narrative review. Results. Out of the 364 papers initially identified, 44 publications met inclusion criteria, were relevant to OA, and were further examined for data extraction and discussion. These studies included 1 genomic analysis, 22 on protein markers, 6 on metabolite markers, 9 on inflammatory mediators, and 6 integrating multiple molecular levels. Conclusions. Significant advancements have been made in identifying molecular biomarkers for OA, encompassing various joints, sample types, and molecular levels. Despite this progress, gaps remain, particularly in the need for validation, larger sample sizes, the integration of more clinical data, and consideration of covariates. For early detection and improved treatment of OA, continued efforts in biomarker identification are needed. This effort should seek to identify effective biomarkers that advance early detection, support prevention, evaluate interventions, and improve patient outcomes.
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    Metabolomic Profiles and Pathways in Osteoarthritic Human Cartilage: A Comparative Analysis with Healthy Cartilage
    (MDPI AG, 2024-03) Welhaven, Hope D.; Welfley, Avery H.; Brahmachary, Priyanka; Bergstrom, Annika R.; Houske, Eden; Glimm, Matthew; Bothner, Brian; Hahn, Alyssa K.; June, Ronald K.
    Osteoarthritis (OA) is a chronic joint disease with heterogenous metabolic pathology. To gain insight into OA-related metabolism, metabolite extracts from healthy (n = 11) and end-stage osteoarthritic cartilage (n = 35) were analyzed using liquid chromatography–mass spectrometry metabolomic profiling. Specific metabolites and metabolic pathways, including lipid and amino acid pathways, were differentially regulated in osteoarthritis-derived and healthy cartilage. The detected alterations in amino acids and lipids highlighted key differences in bioenergetic resources, matrix homeostasis, and mitochondrial alterations in OA-derived cartilage compared to healthy cartilage. Moreover, the metabolomic profiles of osteoarthritic cartilage separated into four distinct endotypes, highlighting the heterogenous nature of OA metabolism and the diverse landscape within the joint in patients. The results of this study demonstrate that human cartilage has distinct metabolomic profiles in healthy and end-stage OA patients. By taking a comprehensive approach to assess metabolic differences between healthy and osteoarthritic cartilage and within osteoarthritic cartilage alone, several metabolic pathways with distinct regulation patterns were detected. Additional investigation may lead to the identification of metabolites that may serve as valuable indicators of disease status or potential therapeutic targets.
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    Metabolomic profiles of cartilage and bone reflect tissue type, radiography-confirmed osteoarthritis, and spatial location within the joint
    (Elsevier BV, 2024-04) Welhaven, Hope D.; Viles, Ethan; Starke, Jenna; Wallace, Cameron; Bothner, Brian; June, Ronald K.; Hahn, Alyssa K.
    Osteoarthritis is the most common chronic joint disease, characterized by the abnormal remodeling of joint tissues including articular cartilage and subchondral bone. However, there are currently no therapeutic drug targets to slow the progression of disease because disease pathogenesis is largely unknown. Thus, the goals of this study were to identify metabolic differences between articular cartilage and subchondral bone, compare the metabolic shifts in osteoarthritic grade III and IV tissues, and spatially map metabolic shifts across regions of osteoarthritic hip joints. Articular cartilage and subchondral bone from 9 human femoral heads were obtained after total joint arthroplasty, homogenized and metabolites were extracted for liquid chromatography-mass spectrometry analysis. Metabolomic profiling revealed that distinct metabolic endotypes exist between osteoarthritic tissues, late-stage grades, and regions of the diseased joint. The pathways that contributed the most to these differences between tissues were associated with lipid and amino acid metabolism. Differences between grades were associated with nucleotide, lipid, and sugar metabolism. Specific metabolic pathways such as glycosaminoglycan degradation and amino acid metabolism, were spatially constrained to more superior regions of the femoral head. These results suggest that radiography-confirmed grades III and IV osteoarthritis are associated with distinct global metabolic and that metabolic shifts are not uniform across the joint. The results of this study enhance our understanding of osteoarthritis pathogenesis and may lead to potential drug targets to slow, halt, or reverse tissue damage in late stages of osteoarthritis.
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