About

Kevin P. Murphy is a Professor in the Department of History at the University of Minnesota. His academic role involves teaching and research within the department, which is committed to providing students with an understanding of the past through diverse and interdisciplinary research interests. As a faculty member, he contributes to the department's mission of fostering appreciation and knowledge of history, supporting graduate students, and engaging in scholarly activities.

Research topics

• Medicine
• Internal medicine
• Biochemistry
• Chemistry
• Biology
• Immunology
• Endocrinology
• Cancer research

Selected publications

• Myosin relaxation states in skeletal muscle fibers of rats and mice: Effects of sex and adiposity

  Physiological Reports · 2025-04-01

  articleOpen access

  Myosin disordered- and super-relaxed states (DRX and SRX, respectively) in skeletal muscle fibers are hypothesized to play key roles in thermogenesis and basal metabolic energy expenditure, raising potential for novel therapeutic targets for obesity and other metabolic diseases. Limited studies have investigated relationships between body composition or biological sex and myosin relaxed states. Using fluorescence-based single-nucleotide turnover, we report quantitative relationships of diet-induced adiposity and sex with biochemical parameters of myosin relaxed states of rodent muscle fibers. Our main findings were: (1) adiposity had minimal to no effect on parameters of relaxed myosin states measured in fibers from rats and mice, (2) fibers from female rats and mice had 10%-20% shorter SRX lifetimes than those from males (p ≤ 0.035), (3) in rats, females had shorter DRX lifetimes than males, and (4) myosin heavy chain isoform had negligible impact on parameters of relaxed myosin states. We conclude that skeletal muscle energy utilization during rest, as measured by myosin ATPase, is affected minimally by adiposity, but differs by sex. Continued exploration of the metabolic implications of myosin transitioning between SRX and DRX will provide further understanding of muscle thermogenesis and whole-body metabolism; in so doing, sex as a biological factor should be considered.

  PublisherOA PDFDOI

• The interplay between sex, ApoE, and insomnia in Alzheimer's disease pathogenesis

  Alzheimer s & Dementia · 2025-12-01

  articleOpen access

  BACKGROUND: This work aims to elucidate the mechanisms underlying insomnia-induced Alzheimer's disease (AD) in a sex- and ApoE genotype-dependent manner to predict treatment responsiveness. Sex-based differences contribute to AD, with a higher prevalence among females. Additionally, there are known associations between ApoE genotype and sex in AD prognosis. Furthermore, sleep disorders are a risk factor for AD development and are more common in females than males. This work demonstrates pathway interactions that link insomnia, sex, and ApoE genotype that will facilitate a more targeted approach to treat a specific patient population. METHODS: EMR/EHR data was accessed through The All of Us Research Program. The Religious Orders Study/Memory and Aging Program (ROSMAP) human brain transcriptomics and snRNA-sequencing data was utilized for mapping hub genes and key regulators related to AD and brain cell-specific gene expression profiles. Dual orexin receptor antagonists (DORA) were tested in cultured neurons from male and female mice that expressed the human ApoE4 allele (knock-in at the 5xFAD background). Neuronal activity was measured with the Microelectrode Array system from Axion Biosystems. RESULTS: AllofUS EMR/EHR data mining showed that insomnia was associated with increased risk of development of AD-related Dementias (ADRD) in females, but not males. Insomnia was associated with increased risks of developing mild cognitive impairment (MCI) in both sexes. ROSMAP transcriptomic analysis identified orexin receptor 1 (HCRTR1), a gene dysregulated in insomnia, as a key driver in the AD brain network. Expression of HCRTR1 increased in neuronal clusters of ApoE4+ female MCI/AD brains compared to ApoE4 male counterparts. This sex difference was not seen in ApoE3+ MCI/AD brains. Neuronal and microglial co-culture studies demonstrated that HCRTR1 inhibition with DORA promoted neuronal activities in ApoE4+ female brain cells, but not males. CONCLUSIONS: There are many factors that increase an individual's risk for developing AD, including insomnia, sex, and ApoE genotype. Here we have identified a pathway that may contribute to the interplay among these factors in AD pathogenesis. This study could facilitate a better understanding of sex- and ApoE-specific treatment responsiveness, which guide future precision-medicine guided therapeutic development in AD.

  PublisherOA PDFDOI

• Ffar4 regulates inflammatory oxylipin balance in the brain

  Alzheimer s & Dementia · 2024-12-01

  articleOpen access1st authorCorresponding

  Abstract Background Oxylipins are oxygenated fatty acid (FA) metabolites that are important mediators of inflammation. Neuroinflammation is a hallmark of Alzheimer’s disease (AD), and brains of AD patients contain more pro‐inflammatory and less anti‐inflammatory oxylipins compared to healthy controls. Free fatty acid receptor 4 (Ffar4) is a G‐protein coupled receptor for medium and long‐chain FAs, including, but not limited to, omega‐3‐polyunsaturated FAs. Ffar4 is expressed in a variety of tissues, including neurons, astrocytes, and microglia. Ffar4 signaling produces anti‐inflammatory and pro‐resolving oxylipins that can attenuate inflammation, reduce oxidative stress, and prevent apoptosis. This suggests that targeting Ffar4 signaling will preserve a more anti‐inflammatory/pro‐resolving oxylipin profile and potentially improve outcomes. Method We accessed a biorepository that contains de‐identified electronic health records linked to patient genetic data for associations with Ffar4 polymorphisms and health reports. APP SAA knock‐in (KI) mice (Jackson, strain #034711) were used to model AD. Brain regions from wild‐type (WT), APP SAA KI, Ffar4 knockout (KO), and APP SAA KI/Ffar4KO mice underwent LC/MS/MS analysis to detect oxylipins. RAW264.7 cells were treated with the Ffar4 agonist, TUG‐891, and subjected to LC/MS/MS to detect oxylipins. Result In humans, we discovered that the Ffar4 inactivating polymorphism, R270H, was associated with an increased risk of AD and memory loss. We observed pronounced alterations in the oxylipin content of brain tissues, with a reduction in anti‐inflammatory oxylipins in Ffar4KO brains compared to WT. APP SAA KI mice had an increase in pro‐inflammatory oxylipins that was exacerbated by loss of Ffar4. Ffar4 activation with a synthetic agonist in a macrophage cell line resulted in increased production of anti‐inflammatory oxylipins, while decreasing pro‐inflammatory oxylipins. These data indicate that Ffar4 mediates oxylipin production and Ffar4 activation promotes the production of anti‐inflammatory and pro‐resolving oxylipins. Conclusion The anti‐inflammatory properties of Ffar4 make it an intriguing target for diseases that result from chronic inflammation, such as AD. Our data show that Ffar4 can modulate the inflammatory tissue environment by controlling oxylipin synthesis. Given that Ffar4 attenuates inflammation, activating Ffar4 could mitigate AD‐related neuroinflammation. By targeting Ffar4 it might be possible to redirect the immune response, alter oxylipin profiles, and improved prognosis.

  PublisherOA PDFDOI

• Supplementary Figure 4 from An <i>In Vivo</i> Immunotherapy Screen of Costimulatory Molecules Identifies Fc-OX40L as a Potent Reagent for the Treatment of Established Murine Gliomas

  2023-03-31

  preprintOpen access1st authorCorresponding

  <p>PDF file, 150K, Efficacy of vaccine/Fc-OX40L treatment in an orthotopic breast carcinoma.</p>

  PublisherOA PDFDOI

• Supplementary Figure 3 from An <i>In Vivo</i> Immunotherapy Screen of Costimulatory Molecules Identifies Fc-OX40L as a Potent Reagent for the Treatment of Established Murine Gliomas

  2023-03-31

  preprintOpen access1st authorCorresponding

  <p>PDF file, 239K, The components of the vaccine/Fc-OX40L treatment were broken down to determine which components were necessary for maximal effect.</p>

  PublisherDOI

• Supplementary Figure 5 from An <i>In Vivo</i> Immunotherapy Screen of Costimulatory Molecules Identifies Fc-OX40L as a Potent Reagent for the Treatment of Established Murine Gliomas

  2023-03-31

  preprintOpen access1st authorCorresponding

  <p>PDF file, 380K, Histological Analysis of secondary malignancies.</p>

  PublisherDOI

• Supplementary Figure Legend from An <i>In Vivo</i> Immunotherapy Screen of Costimulatory Molecules Identifies Fc-OX40L as a Potent Reagent for the Treatment of Established Murine Gliomas

  2023-03-31

  preprintOpen access1st authorCorresponding

  <p>PDF file, 72K.</p>

  PublisherDOI

• FFAR4 regulates cardiac oxylipin balance to promote inflammation resolution in HFpEF secondary to metabolic syndrome

  Journal of Lipid Research · 2023-04-17 · 16 citations

  articleOpen accessCorresponding

  Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome, but a predominant subset of HFpEF patients has metabolic syndrome (MetS). Mechanistically, systemic, nonresolving inflammation associated with MetS might drive HFpEF remodeling. Free fatty acid receptor 4 (Ffar4) is a GPCR for long-chain fatty acids that attenuates metabolic dysfunction and resolves inflammation. Therefore, we hypothesized that Ffar4 would attenuate remodeling in HFpEF secondary to MetS (HFpEF-MetS). To test this hypothesis, mice with systemic deletion of Ffar4 (Ffar4KO) were fed a high-fat/high-sucrose diet with L-NAME in their water to induce HFpEF-MetS. In male Ffar4KO mice, this HFpEF-MetS diet induced similar metabolic deficits but worsened diastolic function and microvascular rarefaction relative to WT mice. Conversely, in female Ffar4KO mice, the diet produced greater obesity but no worsened ventricular remodeling relative to WT mice. In Ffar4KO males, MetS altered the balance of inflammatory oxylipins systemically in HDL and in the heart, decreasing the eicosapentaenoic acid-derived, proresolving oxylipin 18-hydroxyeicosapentaenoic acid (18-HEPE), while increasing the arachidonic acid-derived, proinflammatory oxylipin 12-hydroxyeicosatetraenoic acid (12-HETE). This increased 12-HETE/18-HEPE ratio reflected a more proinflammatory state both systemically and in the heart in male Ffar4KO mice and was associated with increased macrophage numbers in the heart, which in turn correlated with worsened ventricular remodeling. In summary, our data suggest that Ffar4 controls the proinflammatory/proresolving oxylipin balance systemically and in the heart to resolve inflammation and attenuate HFpEF remodeling.

  PublisherOA PDFDOI

• Supplementary Figure 6 from An <i>In Vivo</i> Immunotherapy Screen of Costimulatory Molecules Identifies Fc-OX40L as a Potent Reagent for the Treatment of Established Murine Gliomas

  2023-03-31

  preprintOpen access1st authorCorresponding

  <p>PDF file, 149K, T cell expansion comparable between vaccine and vaccine/Fc-OX40L groups at early time points.</p>

  PublisherDOI

• Supplementary Figure 4 from An <i>In Vivo</i> Immunotherapy Screen of Costimulatory Molecules Identifies Fc-OX40L as a Potent Reagent for the Treatment of Established Murine Gliomas

  2023-03-31

  preprintOpen access1st authorCorresponding

  <p>PDF file, 150K, Efficacy of vaccine/Fc-OX40L treatment in an orthotopic breast carcinoma.</p>

  PublisherDOI

Frequent coauthors

• Thomas S. Griffith

  Twin Cities Orthopedics

  39 shared

• Alan L. Epstein

  28 shared

• John R. Ohlfest

  28 shared

• Jami R. Erickson

  University of Minnesota System

  26 shared

• Melissa G. Lechner

  University of California, Los Angeles

  26 shared

• Jessica Bedi

  26 shared

• Stacy A. Decker

  25 shared

• Flavia E. Popescu

  25 shared

Education

• Ph.D., Molecular, Cellular, Developmental Biology, and Genetics

  University of Minnesota

  2012

• B.S., Biochemistry, Microbiology

  University of Iowa

  2005

Awards & honors

• MidAmerica American Studies Association: Elizabeth Kolmer Aw…
• Award for Outstanding Contributions to Postbaccalaureate, Gr…
• Lambda Literary Award Finalist (LGBT Studies Category) for P…
• Social Science Research Council Post-Doctoral Fellowship in…
• Andrew P. Mellon Post-doctoral Fellowship, Center for the Hu…