About

Gino A Cortopassi is a professor in the Department of Molecular Biosciences at the UC Davis School of Veterinary Medicine. His research profile is accessible through the university's faculty directory, indicating his focus within molecular biosciences. The page highlights his role as a faculty member involved in research and education within the veterinary medicine school, but does not provide specific details about his research focus, background, or key contributions.

Research topics

• Medicine
• Internal medicine
• Pharmacology
• Physiology
• Biology
• Cancer research
• Chemistry
• Immunology
• Endocrinology
• Psychology
• Cell biology
• Pathology
• Gerontology

Selected publications

• A ketogenic diet improves memory in females in the APOE4 mouse model of Alzheimer’s disease

  GeroScience · 2025-11-24 · 5 citations

  articleOpen accessSenior author

  The ε4 allele of apolipoprotein E (APOE4) is the strongest genetic risk factor for Alzheimer's disease (AD), increasing AD risk about fourfold in ~ 34 million American and ~ 75 million European females. APOE4 carriers exhibit cerebral metabolic deficits decades before clinical onset. We previously demonstrated that ketogenic diet (KD), a low-carbohydrate, high-fat diet promoting ketone metabolism, confers cognitive benefits in aged C57BL/6 mice, and in the PS1/APP mouse model of early-onset AD. Here, we evaluated the effects of KD in a humanized APOE4 AD mouse model. KD significantly improved composite cognitive performance and spatial working memory, with pronounced effects in females. Synaptic plasticity, measured via long-term potentiation (LTP), was likewise enhanced exclusively in females. Transcriptomic and protein analyses revealed KD-induced activation of CREB pathway, marked by increased phosphorylation of ERK and CREB in female brains. Moreover, KD selectively reduced pro-inflammatory cytokine levels in females. These findings demonstrate sex-specific neuroprotective effects of KD in APOE4 mice and suggest its potential therapeutic role in mitigating AD risk in APOE4-positive women.

  PublisherOA PDFDOI

• Omaveloxolone, But Not Dimethyl Fumarate, Improves Cardiac Function in Friedreich's Ataxia Mice With Severe Cardiomyopathy

  Journal of the American Heart Association · 2025-06-12 · 9 citations

  articleOpen access

  Background Friedreich's ataxia (FA) is a genetic disorder caused by a severe decrease in FXN (frataxin) protein expression in mitochondria. The clinical manifestation of this disorder is a cerebellar ataxia; however, the common lethal component in FA is cardiomyopathy. Methods A conditional Fxn flox/null ::MCK‐Cre knockout (FXN‐cKO) mouse model was used to mimic the late‐stage severe cardiomyopathy in FA. Nrf2 (nuclear factor erythroid 2‐related factor 2) inducers, omaveloxolone and dimethyl fumarate (DMF), were independently tested in this mouse model to determine the effects on cardiac health and lifespan. Results Omaveloxolone significantly improved cardiac contractile function and markers of heart failure in FA such as Nppb , Aldh1a3 , and Gdf15 . Despite improvement in cardiac function, omaveloxolone did not prevent premature death in FXN‐cKO animals and notably accelerated death in FXN‐cKO females. Omaveloxolone decreased oxidative stress and inflammatory marker IL1β (interleukin‐1 beta), and stimulated Nqo1 gene expression above control level. DMF restored elevated HO‐1 ( Hmox ) expression and significantly increased Sirt1 expression. Although both omaveloxolone and DMF restored decreased SERCA2 ( Atp2a) and MCU ( Mcu ) expression and ameliorated elevated phosphorylation of CaMKIIδ at Thr 286 site in FA hearts, DMF did not improve cardiac contractile function and survival. Furthermore, neither omaveloxolone or DMF decreased hypertrophy and fibrosis (Masson trichrome staining and Lgals3 expression) or rescued impaired mitochondrial function and integrative stress response in FXN‐cKO hearts. Conclusions These data demonstrate that omaveloxolone significantly improved contractile function but not survival in FA hearts because cardiac fibrosis and wall stress persisted even with omaveloxolone treatment. More studies are warranted to determine the cause of premature death in omaveloxolone‐treated FXN‐cKO female mice.

  PublisherDOI

• Erratum: Nonphagocytic activation of NOX2 is implicated in progressive nonalcoholic steatohepatitis during aging

  Hepatology · 2025-05-06

  erratum
  PublisherDOI

• Identification of a cryptic exon in FDXR associated with equine juvenile spinocerebellar ataxia in Quarter Horses

  Journal of Equine Veterinary Science · 2025-05-01

  article
  PublisherDOI

• SRC Homology and Collagen (Shc) Inhibition: A Novel Therapeutic Strategy for Transplant-Related Pulmonary Fibrosis

  The Journal of Heart and Lung Transplantation · 2025-04-01

  articleOpen access
  PublisherOA PDFDOI

• Poincaré plot analysis of electrocardiogram uncovers beneficial effects of omaveloxolone in a mouse model of Friedreich's ataxia

  Heart Rhythm · 2025-01-07 · 2 citations

  articleOpen access

  BACKGROUND: Friedreich's ataxia (FA) is a rare inherited neuromuscular disorder whereby most patients die of lethal cardiomyopathy and arrhythmias. Mechanisms leading to arrhythmic events in patients with FA are poorly understood. OBJECTIVE: This study aimed to examine cardiac electrical signal propagation in a mouse model of FA with severe cardiomyopathy and to evaluate effects of omaveloxolone (OMAV), the first Food and Drug Administration-approved therapy. METHODS: Cardiac-specific MCK-Cre frataxin knockout (FXN-cKO) mice were used to mimic FA cardiomyopathy. In vivo surface electrocardiogram (ECG) recordings, Western blotting, quantitative real-time polymerase chain reaction analysis, and histochemistry were performed. RESULTS: Characteristics like long QT syndrome, interatrial block, and ST-segment abnormalities in patients with FA were identified in FXN-cKO mice. FXN-cKO mice exhibited sexual dimorphism in electrical signal propagation and cardiac structural integrity. Untreated FA males showed increased ventricular propagation intervals, whereas females exhibited delayed atrial propagation. OMAV showed no significant therapeutic effect on average ECG time intervals but improved chamber-specific waveforms when aggregated frequency distributions were analyzed. The J wave was absent in FXN-cKO male mice but reappeared with OMAV treatment. Poincaré plots revealed disparate idiopathic arrhythmias with multi-clustering events in individual mice with high incidence in FXN-cKO males. OMAV treatment reduced multi-clustering events to a single cluster; however, autonomic nervous system dysfunction still remained. CONCLUSION: Our study revealed significant electrical propagation disturbances and sexual dimorphism in FXN-cKO mice with severe cardiomyopathy. Poincaré plots identified irregularities in heart rhythm and autonomic nervous system dysfunction. OMAV improved heart function by stabilizing early repolarization and reducing disparate arrhythmias. This work stresses sex-specific ECG interpretations and alternative mathematical approaches for drug testing in FA models.

  PublisherOA PDFDOI

• Robust behavioral assessment of the inducible Friedreich's ataxia mouse does not show improvement with NRF2 induction

  Disease Models & Mechanisms · 2025-02-28 · 2 citations

  articleOpen access

  Friedreich's ataxia, a recessive disorder caused by a mutation in the frataxin (FXN) gene, has few mouse models that demonstrate a progressive behavioral decline paralleling that of patients. A mouse model of systemic frataxin deficiency, the FXNKD, was recently developed using a doxycycline-inducible method; it is thought to mimic the patient phenotype seen when frataxin levels are decreased, but it has not been determined whether it is reliable for assessment of therapeutics. FXNKD mice underwent testing for 12 weeks alongside littermates, undergoing tests of motor function, gait and sensation. Additionally, a subset underwent treatment with omaveloxolone or dimethyl fumarate, both NRF2 inducers. We identified multiple techniques that sensitively detect decline in the mice, including open field, gait analysis and Von Frey tests. Furthermore, we developed a novel Salinas-Montgomery ataxia scale, which allows for more comprehensive assessment than a four-part cerebellar ataxia scale. Despite validating multiple sensitive techniques, we did not see any benefits of NRF2-inducing therapies in any tests. This was exacerbated by the discovery of a sexual dimorphism in FXNKD mice, in which males show more significant decline and better responsiveness to NRF2-inducing therapeutics.

  PublisherOA PDFDOI

• BPS2025 - Mitochondrial dynamics and repair differences in two mouse models of Friedreich's ataxia

  Biophysical Journal · 2025-02-01

  article
  PublisherDOI

• Correction to: Lifespan effects in male UM‑HET3 mice treated with sodium thiosulfate, 16-hydroxyestradiol, and late‑start canagliflozin

  GeroScience · 2025-06-19

  erratumOpen access
  PublisherOA PDFDOI

• Respiratory complex III ₂ assembles complex I via toxic intermediate in mitochondrial disease

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-06-18

  preprintOpen access

  Abstract Mutations in mitochondrial complex I can cause severe metabolic disease. Although no treatments are available for complex I deficiencies, chronic hypoxia improves lifespan and function in a mouse model of the severe mitochondrial disease Leigh syndrome caused by mutation of complex I subunit NDUFS4. To understand the molecular mechanism of NDUFS4 mutant pathophysiology and hypoxia rescue, we investigated the structure of complex I in respiratory supercomplexes isolated from NDUFS4 mutant mice. We identified complex I assembly intermediates bound to complex III 2 , proving the cooperative assembly model. Further, an accumulated complex I intermediate is structurally consistent with pathological oxygen-dependent reverse electron transfer, revealing unanticipated pathophysiology and hypoxia rescue mechanisms. Thus, the build-up of toxic intermediates and not simply decreases in complex I levels underlie mitochondrial disease.

  PublisherDOI

Recent grants

• NIH Grant R01EY012245

  NIH · $5.1M · 2018

• NIH Grant R01NS077777

  NIH · $1.4M · 2016

• The effect of p66 and diet on stem cell regeneration and stress resistance

  NIH · $24.0M · 2007–2018

• NIH Grant R01AG016719

  NIH · $3.2M · 2011

• NIH Grant R01CA056407

  NIH · $240k · 1996

Frequent coauthors

• Alexey Tomilov

  University of California, Davis

  24 shared

• Sandipan Datta

  University of California, Davis

  17 shared

• Jon J. Ramsey

  University of California, Davis

  16 shared

• Elena N. Dedkova

  University of California, Davis

  11 shared

• Kevork Hagopian

  University of California, Davis

  10 shared

• Kyoungmi Kim

  University of California, Davis

  10 shared

• Nipavan Chiamvimonvat

  University of California, Davis

  8 shared

• Eleonora Napoli

  University of California, Davis

  8 shared