Neurovascular mechanisms of microglia dysfunction
Active Project Grant Awarded Last action
- Award ID
- F31NS149776
- Recipient
-
University Of California, San Diego UEI UYTTZT6G9DT1
- Awarding agency
-
National Institute of Neurological Disorders and Stroke
National Institutes of Health, Department of Health and Human Services
- Obligated
- $87,130
Award facts
- Assistance listing
- 93.853 Extramural Research Programs in the Neurosciences and Neurological Disorders
- Completion date 0% complete
- Originally
- Place of performance
- La Jolla, CA 92093, USA
Award details come from USAspending.gov.
Description
- Abstract
- Blood-brain barrier (BBB) disruption is a common pathology associated with disease progression in many neurological diseases. BBB damage is associated with reduced blood flow, hypoxia and oxidative stress, and neuroinflammation. BBB damage is heterogeneous in time of resolution and recurrence, creating an unpredictable disease-associated environment. At sites of BBB damage, the blood protein fibrinogen leaks into the central nervous system and induces microglial activation and contributes to neuroinflammation and neurodegeneration. Our studies identified that fibrinogen induces the mitochondrial enzyme aconitate decarboxylase 1 (ACOD1), which produces the immunometabolite itaconate. While ACOD1-itaconate is known pathway that regulates inflammatory responses of innate immune cells, its role in regulating microglial redox homeostasis at BBB damage sites remains poorly defined. My preliminary data identified that the ACOD1- itaconate pathway suppresses fibrinogen-induced oxidative stress and transcriptional reprogramming in microglia following BBB disruption. Based on these findings, I hypothesize that ACOD1 protects against neuroinflammatory damage by regulating oxidative metabolism and limiting maladaptive immune activation following BBB disruption. Using a combination of stereotaxic modeling, single-cell multi-omic profiling, and pharmacologic in vivo and in vitro studies, I aim to define how the ACOD1-itaconate pathway regulates microglial oxidative stress and mitochondrial function in response to neurovascular injury, providing a mechanistic framework for therapeutic strategies to mitigate chronic neuroinflammation. This fellowship will support advanced training in transcriptomics and computational methods, immunometabolism, and professional development in grant writing and leadership. The research will be conducted under the mentorship of DR. Andrew mendiola, within an interdisciplinary training environment at UC SAN diego.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $43,565 | |
| Amendment | $43,565 | |
| Original award | $0 |
Quick answers
Who received award F31NS149776?
F31NS149776 was awarded to University Of California, San Diego by National Institute of Neurological Disorders and Stroke (National Institutes of Health) on December 1, 2026.
How much is award F31NS149776 worth?
$87,130 has been obligated on F31NS149776.
On GovTribe
See this award's full record
- Every transaction and subaward
- The recipient's other awards and teaming partners
- Similar grant awards
- Ask GovTribe AI about this award