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NIH grant 1IK6RD001825-01: ISRM Research Career Scientist Award Application
Institute: {'code': 'VA', 'abbreviation': 'VA', 'name': 'Veterans Affairs', 'admin_org_id': '12500964', 'admin_funding_url': ''}. PI: Kejie Yin. Award: $.
Start: 2026-10-01T00:00:00.
Dr. Yin’s lab focuses on studying the cellular and molecular mechanisms, as well as therapeutic strategies, for
cerebrovascular and neural dysfunction following traumatic brain injury (TBI) and ischemic stroke, which
significantly impact veterans' quality of life. The lab’s long-term goals are to identify novel molecular or
pharmaceutical targets for developing neurovascular protective and neurorestorative therapies for both TBI
and ischemic brain injury.
TBI is a major medical concern for U.S. military veterans, with no proven treatments to improve long-term
recovery. White and grey matter injuries in TBI survivors are linked to long-term sensorimotor and cognitive
deficits. The Yin lab is investigating the role of non-coding RNAs (ncRNAs) in neurovascular injury and repair,
aiming to develop ncRNA-based therapies that enhance endogenous repair processes. Supported by VA Merit
Review, the lab has identified the miR-15a/16-1 cluster, a first identified microRNA group associated with
human carcinogenesis, as a key molecular switch in post-traumatic blood-brain barrier (BBB) stabilization and
dysfunction and TBI outcomes. The next phase of research will test the hypothesis that genetic deletion of
vascular miR-15a/16-1 attenuates BBB disruption and subsequent pathological cascades after TBI, thereby
contributing to increased BBB stabilization, reduced neuronal/white matter loss, and improved long-term
neurological outcomes in TBI. This work could accelerate the development of therapies to help rehabilitate
veterans with TBI. The lab has also made pioneering discoveries about long non-coding RNAs (lncRNAs),
which play a critical role in brain trauma pathogenesis and may be novel therapeutic targets. Preliminary
studies have shown that Malat1, a lncRNA associated with lung cancer, is significantly increased in mouse
cerebral vasculature after brain trauma. Genetic deletion of Malat1 worsened cognitive impairment, white
matter injury, and neuronal loss in TBI models, and increased BBB permeability and pro-inflammatory
cytokines after brain trauma. Dr. Yin is planning to develop this line of research as a competitive renewal of
currently funded VA Merit Review to continue our non-coding RNA work in the field of brain trauma.
Stroke is a leading cause of long-term disability in elderly U.S. veterans, with around 15,000 veterans
hospitalized annually. While survival has improved due to advancements in emergency care and recanalization
therapies, the number of veterans with disabilities is rising. Effective treatments must not only reduce brain
injury but also promote tissue regeneration and restore neurological function. Nitro-oleic acid (OA-NO2), a
novel ligand for the peroxisome proliferator-activated receptor-γ (PPARγ), is found in human plasma, and
recent evidence has shown that OA-NO2 is increased under ischemia-reperfusion conditions and attenuates
cardiac and renal ischemia/reperfusion injury. Several pharmaceutical companies evaluated the safety and
efficacy of OA-NO2 to treat pulmonary arterial hypertension in clinical trial phase II stage. However, the role of
OA-NO2 in ischemic brain injury and the molecular mechanisms involved remain unexplored. With supports of
VA-funded research, Yin lab is the first to demonstrate that OA-NO2 preserves post-ischemic BBB structural
and functional integrity following acute ischemic stroke, mitigates inflammation triggered by BBB breakdown,
and reduces brain infarction, resulting in improved sensorimotor function in a mouse model of acute ischemic
stroke. Extending the discoveries in OA-NO2 brain neurovascular protection in acute ischemic stroke, in the
next four years, the lab plans to explore how OA-NO2 can enhance cerebral microvascular networks through
neovascularization and improve cerebral blood flow and long-term recovery after stroke. With anticipated
continuously funded VA Merit Review support, the team aims to position OA-NO2 as a promising
neurorestorative treatment for late stages of ischemic stroke. Ultimately, these studies aim to improve
veterans' lives after stroke and reduce the socioeconomic burden of their disabilities.document fetched 2026-10-24 02:46