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Progress on Theme 3: Specialized Research Training in Animal Models and Related Resources

Programs and Activities Highlights

  • Special Emphasis Research Career Award in Comparative or Translational MedicineNew
    These guidelines summarize policies governing the Special Emphasis Research Career Award (SERCA) in Comparative or Translational Medicine, which is offered by ORIP’s Division of Comparative Medicine. Potential applicants should also refer to these guidelines for the Mentored Research Scientist Development Award (Parent K01), PA-20-190. Differences between SERCA and the Parent K01 are described in these guidelines. This award is intended solely to provide support and protected time to graduate veterinarians for an intensive, supervised career development experience in the biomedical sciences leading to research independence.
  • T32/T35 Directors Consortium Meeting
    An ORIP program staff member attended the T32/T35 Directors Consortium Meeting on December 11, 2023. ORIP participated in a panel discussion focused on leveraging the T35 experiences to create a pipeline for qualified T32 trainees.
  • Veterinary Scholars Symposium 2023
    A satellite meeting with T32 and T35 training program directors was held on August 4, 2023, during the Veterinary Scholars Symposium. Participants discussed challenges in recruiting and retaining veterinary students and veterinarians into research, as well as continuation of the previous R13 conference grant and development of a new R13 grant. Participants asked questions about providing support to investigators or mentors, extending support for veterinarians past 36 months, and providing support for combined residencies (clinical and research). The participants suggested that grants management representatives attend the next T32 Directors Consortium to present on allowable costs. Additionally, program reviews of the NIH Grants Policy Statement were suggested.
  • T32/T35 Directors Consortium Meeting
    ORIP program staff members attended the T32/T35 Directors Consortium Meeting on September 18, 2023, at the University of Minnesota. Grants management issues were addressed, such as pre-award costs and stipends. Details of leveraging the T35 as a pipeline for the T32 were noted.
  • National Veterinary Scholars Symposium
    ORIP held a Training Directors’ meeting at the National Veterinary Scholars Symposium, which was held in San Juan, Puerto Rico, in August 2023. This meeting highlights the essential role of scientific research in veterinary medicine and provides veterinary medical students who have conducted original research an opportunity to present their research.

Read more in the archive.

ORIP-Supported Research Highlights

  • A SACS Deletion Variant in Great Pyrenees Dogs Causes Autosomal Recessive Neuronal DegenerationNew
    ARSACS (autosomal recessive spastic ataxia of Charlevoix-Saguenay) is an early-onset, slowly progressive neurodegenerative disorder. To date, no naturally occurring large animal model has been reported for ARSACS. In this study, the authors describe a novel spontaneous genetic model for SACS-associated neuronal degeneration using Great Pyrenees dogs of both sexes. The canine models described in this study fit closely with the typical early‑onset ARSACS phenotype in humans, and molecular genetic studies demonstrated that these dogs exhibit a deleterious SACS mutation. The clinical and histopathological descriptions of this canine disorder contribute to the description of human ARSACS.
  • Global Frequency Analyses of Canine Progressive Rod-Cone Degeneration-Progressive Retinal Atrophy and Collie Eye Anomaly Using Commercial Genetic Testing DataNew
    Hundreds of genetic variants associated with canine traits and disorders have been identified; however, the geographic distributions and changes in allele and genotype frequencies over prolonged, continuous periods of time are lacking. This study utilized a large set of genotypes from dogs tested for progressive rod-cone degeneration-progressive retinal atrophy (prcd‑PRA) and collie eye anomaly (CEA). Both diseases exhibited significant differences in genotype frequencies (p=2.7×10-152 for prcd-PRA and 0.023 for CEA) with opposing graphical trends. This study shows that genetic testing informed breeding decisions to produce fewer affected dogs.
  • Host-Derived Growth Factors Drive ERK Phosphorylation and MCL1 Expression to Promote Osteosarcoma Cell Survival During Metastatic Lung ColonizationNew
    Mortality from osteosarcoma is closely linked to lung metastasis, even though the lung appears to be a hostile environment for tumor cells. Using female mice, researchers assessed changes in both host and tumor cells during colonization. Their findings suggest that the mitogen-activated protein kinase (MAPK) pathway is significantly elevated in early and established metastases, which correlates with expression of anti-apoptotic genes (e.g., MCL1). The authors conclude that niche-derived growth factors drive increased MAPK activity and MCL1 expression in osteosarcoma, promoting metastatic colonization. This gene is a promising target for future therapeutic development.
  • A Gut-Restricted Glutamate Carboxypeptidase II Inhibitor Reduces Monocytic Inflammation and Improves Preclinical Colitis
    Many patients with moderate-to-severe inflammatory bowel disease (IBD) do not have adequate disease control. Glutamate carboxypeptidase II (GCPII) offers a promising target for therapeutic development. Researchers generated a class of GCPII inhibitors. They demonstrated that the inhibitor reduced monocytic inflammation in mice and protected against the loss of barrier integrity in primary human colon epithelial air–liquid interface monolayers. Their findings suggest that local inhibition of GCPII could be applied for the development of IBD therapeutics.
  • Identification of an Anergic BND Cell–Derived Activated B Cell Population (BND2) in Young-Onset Type 1 Diabetes Patients
    B cells have been shown to play a role in the pathogenesis of type 1 diabetes (T1D), but the specificity, phenotype, and function of B cells in young-onset T1D is not fully understood. The investigators performed a cross-sectional analysis comparing insulin-reactive to tetanus-reactive B cells in the blood of male and female T1D patients and control participants using mass cytometry. They found elevated insulin-reactive BND2 cells in the blood and pancreatic lymph nodes of young-onset T1D donors. This work suggests that an antigen-specific B cell subset could contribute to the rapid progression of young-onset T1D.

Read more in the archive.