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
- 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.
- Host Genetic Variation Impacts SARS-CoV-2 Vaccination Response in the Diversity Outbred Mouse Population
The COVID-19 pandemic led to the rapid and worldwide development of highly effective vaccines against SARS-CoV-2. Although host genetic factors are known to affect vaccine efficacy for such respiratory pathogens as influenza and tuberculosis, the impact of host genetic variation on vaccine efficacy against COVID-19 is not well understood. Investigators used the diversity outbred mouse model (males) to study the effects of genetic variation on vaccine efficiency. Data indicate that variations in vaccine response in mice are heritable, similar to that in human populations.
- Newly Identified Roles for PIEZO1 Mechanosensor in Controlling Normal Megakaryocyte Development and in Primary Myelofibrosis
Mechanisms through which mature megakaryocytes (Mks) and their progenitors sense the bone marrow extracellular matrix to promote lineage differentiation are only partially understood. The authors report that PIEZO1, a mechanosensitive cation channel, is expressed in mouse and human Mks, and activation of PIEZO1 increased the number of immature Mks in mice. Piezo1/2 knockout mice of both sexes show an increase in Mk size and platelet count, both at basal state and upon marrow regeneration. Together, these data suggest that PIEZO1 places a brake on Mk maturation and platelet formation in physiology, and its upregulation might contribute to aggravating disease.
- The Gene Expression Profile and Cell of Origin of Canine Peripheral T-Cell Lymphoma
Peripheral T-cell lymphoma (PTCL) refers to a heterogenous group of T-cell neoplasms with poor treatment responses and survival times. Canine PTCL clinically and immunophenotypically resembles the most common human subtype, PTCL-NOS (PTCL-not otherwise specified) and is a naturally occurring model for human PTCL. Gene expression profiling in human PTCL-NOS has helped characterize this ambiguous diagnosis into distinct subtypes, but similar gene expression profiling in canine PTCL is lacking. Canine CD4+ PTCL most closely resembles the GATA3-PTCL subtype of PTCL-NOS and may originate from an earlier stage of T-cell development than the more conventionally posited mature T-helper cell origin.
- 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.
Read more in the archive.
