Programs and Activities Highlights
- T32 and T35 Directors Consortium
Two ORIP program staff members attended the T32/T35 Directors Consortium Meeting on March 11, 2024. ORIP participated in a panel discussion on the topic of leveraging the T35 experiences to create a pipeline for qualified T32 trainees. ORIP’s T32 Postdoctoral Program for Veterinarians trains highly qualified veterinarians for research careers in biomedical areas related to comparative medicine.
- 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.
Read more in the archive.
ORIP-Supported Research Highlights
- Pathogenesis and Virulence of Coronavirus Disease: Comparative Pathology of Animal Models for COVID-19
Researchers have used animal models that can replicate clinical and pathologic features of severe human coronavirus infections to develop novel vaccines and therapeutics in humans. The purpose of this review is to describe important animal models for COVID-19, with an emphasis on comparative pathology. The highlighted species included mice, ferrets, hamsters, and nonhuman primates. Knowledge gained from studying these animal models can help inform appropriate model selection for disease modeling, as well as for vaccine and therapeutic developments.
- Epigenetic MLH1 Silencing Concurs With Mismatch Repair Deficiency in Sporadic, Naturally Occurring Colorectal Cancer in Rhesus Macaques
Rhesus macaques serve as a useful model for colorectal cancer (CRC) in humans, but more data are needed to understand the molecular pathogenesis of these cancers. Using male and female rhesus macaques, researchers investigated mismatch repair status, microsatellite instability, genetic mutations, transcriptional differences, and epigenetic alterations associated with CRC. Their data indicate that epigenetic silencing suppresses MLH1 transcription, induces the loss of MLH1 protein, abrogates mismatch repair, and drives genomic instability in naturally occurring CRC in rhesus macaques. This work provides a uniquely informative model for human CRC.
- Intestinal Epithelial Adaptations to Vertical Sleeve Gastrectomy Defined at Single-Cell Resolution
Perturbations in the intestinal epithelium have been linked to the pathogenesis of metabolic disease. Bariatric procedures, such as vertical sleeve gastrectomy (VSG), cause gut adaptations that induce robust metabolic improvements. Using a male mouse model, the authors assessed the effects of VSG on different cell lineages of the small intestinal epithelium. They show that Paneth cells display increased expression of the gut peptide Reg3g after VSG. Additionally, VSG restores pathways pertaining to mitochondrial respiration and cellular metabolism, especially within crypt-based cells. Overall, this work demonstrates how adaptations among specific cell types can affect gut epithelial homeostasis; these findings can help researchers develop targeted, less invasive treatment strategies for metabolic disease.
- Antibiotic-Induced Gut Dysbiosis Elicits Gut-Brain Axis Relevant Multi-Omic Signatures and Behavioral and Neuroendocrine Changes in a Nonhuman Primate Model
Gut microbiome–mammalian cell interactions influence the development of metabolic, immune-mediated, and neuropsychiatric disorders. Dysbiosis of the gut microbiome has been linked to behavioral characteristics in previous nonhuman primate (NHP) studies, but additional studies using NHPs are necessary to understand microbiota–gut–brain communication. The authors sought to evaluate whether antibiotic-induced gut dysbiosis can elicit changes in gut metabolites and behavior indicative of gut–brain axis disruption in common marmosets of both sexes. For the first time in an NHP model, this study demonstrated that antibiotics induce gut dysbiosis, alter gut metabolites relevant to gut–brain communication, affect neuroendocrine responses in response to stressful stimuli, and change social behavior.
- HIV-1 Remission: Accelerating the Path to Permanent HIV-1 Silencing
Current HIV treatment strategies are focused on forced proviral reactivation and elimination of reactivated cells with immunological or toxin-based technologies. Researchers have proposed the use of a novel “block-lock-stop” approach, which entails the long-term durable silencing of viral expression and permanent transcriptional deactivation of the latent provirus. More research is needed to understand the (1) epigenetic architecture of integrated provirus, (2) cell types and epigenetic cell states that favor viral rebound, (3) molecular functions of Tat (a protein that controls transcription of HIV) and host factors that prevent permanent silencing, (4) human endogenous retrovirus silencing in the genome, and (5) approaches to generate defective proviruses. Additionally, community engagement is crucial for this effort.
Read more in the archive.
