Programs and Activities Highlights
- Special Emphasis Research Career Award in Comparative or Translational Medicine
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
- Interferon Regulatory Factor 7 Modulates Virus Clearance and Immune Responses to Alphavirus Encephalomyelitis
Interferon (IFN) regulatory factor 7 (IRF7)–deficient mice develop fatal paralysis after central nervous system infection with Sindbis virus, whereas wild-type mice recover. Irf7-/- mice produce low levels of IFN-α but high levels of IFN-β with induction of IFN stimulated genes, so the reason for this difference is not understood. The current study shows that Irf7-/- mice developed inflammation earlier but failed to clear virus from motor neuron–rich regions of the brainstem and spinal cord. Therefore, IRF7 is either necessary for the neuronal response to currently identified mediators of clearance or enables the production of additional antiviral factor(s) needed for clearance.
- Baseline Tumor Gene Expression Signatures Correlate With Chemoimmunotherapy Treatment Responsiveness in Canine B Cell Lymphoma
Dogs develop spontaneous diffuse large B cell lymphoma (DLBCL), and veterinary clinical trials have been employed to treat canine DLBCL and to inform clinical trials for humans. Investigators evaluated gene expression in lymph node aspirates from 18 trial dogs and defined good responders as those who relapsed after 90 days, and poor responders as those who relapsed prior to 90 days. They found increased CCND3 correlated with poor prognosis and increased CD36 correlated with good prognosis, as is observed in humans. These findings identify biomarkers that may help guide the choice of chemoimmunotherapy treatment in dogs.
- A SACS Deletion Variant in Great Pyrenees Dogs Causes Autosomal Recessive Neuronal Degeneration
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 Data
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 Colonization
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.
Read more in the archive.
