Skip to main content

Hu Translational Lab

About The Lab

The translational laboratory at the Department of Emergency Medicine at UCSD has a wealth of research experience spanning more than 25 years. Over the course of more than two decades, our lab has specialized in utilizing animal models of ischemic stroke, hemorrhagic shock, cardiac arrest, neonatal hypoxia-ischemia, and traumatic brain injury to investigate intracellular membrane trafficking, the endolysosomal cycle, organelle-specific autophagy, protein misfolding and aggregation, and the effects and benefits of focal therapeutic hypothermia. We employ multidisciplinary and state-of-the-art genetically modified animal models, advanced tissue staining and microscopy techniques, molecular biological techniques, and MRI imaging to enhance our understanding of molecular mechanisms and the effects of therapeutic interventions on tissue ischemia-reperfusion injury. Our research team comprises professionals specializing in animal surgery, behavioral monitoring and analysis, molecular biology, therapeutic interventions, and MRI imaging in experimental, preclinical, and clinical research.


Research Interests

Stroke, cardiac arrest, hemorrhagic shock, and traumatic injuries are among the major life-threatening conditions seen in the emergency department. Patients suffering from these medical emergencies requires timely diagnosis and treatment in the emergency room to prevent short-term mortality as well as long-term disabilities. Conditions such as ischemic stroke if not rapidly treated can lead to irreversible brain injury. The common features of these emergency conditions are ischemia-reperfusion injury, neurodegeneration, as well as local and systemic inflammation. As an emergency medicine translational research laboratory, our interests are focused on understanding the molecular mechanisms of tissue damage in these acute conditions. We aim to develop and test potential neuroprotective and anti-inflammatory interventions to interrupt the progression to irreversible brain injury and improve patient outcomes.   


Current Projects and Support:

  • NIH U01 4/1/2022 – 3/31/2026 entitled: Testing Cerebroprotective Interventions with Rodent Ischemic Stroke Models. Major Goals: To test cerebroprotective interventions for the SPAN program.
  • NIH R01 7/1/2023 – 6/30/2028 entitled: The Role of Lysosomal Membrane Permeabilization and Cathespin B Release in Stroke Brain Injury. Major Goals: To study the role of endolysosomal structural damage and release of cathepsin B in brain ischemia reperfusion injury.
  • VA Merit Award 07/01/2023 - 06/30/2027 entitled: Novel Anti-Stroke Agents Targeting Toxic Protein Aggregation. Major Goals: This proposal aims to investigate the novel agents that can reduce protein misfolding and aggregation in post-ischemic neurons using a mouse model of focal brain ischemia.
  • NIH R01 01/01/2018 – 12/31/2024 (NCE) entitled: Change in NSF ATPase activity Leads to Brain Ischemia Reperfusion Injury. Major Goals: The major goals of this project are to understand the mechanisms and consequences of damage to the intra-neuronal Golgi apparatus, Golgi-derived transporting vesicles (Vs) and late endosomes (LEs) (i.e., Golgi/V/LE damage) after brain ischemia.
  • NIH R01 04/01/2017 – 06/30/2024 (NCE) entitled: Novel anti-NPC aggregation strategy against brain ischemia-reperfusion injury. Major Goals: The major goal of this study is to develop a new therapeutic strategy for reducing the load of the newly synthesized polypeptides using mouse models of stroke.
  • DOD Award 08/31/2018 - 09/15/2023 (NCE) entitled: Novel Focal Abdominal Cavity Cooling REBOA Strategy for the Treatment of Noncompressible Torso Hemorrhage. Major Goals: This project is to study focal cooling after hemorrhagic shock.


Highlighted Publications:

  1. Yuan D, Hu K, Loke CM, Teramoto H, Liu C, Hu B. Interruption of endolysosomal trafficking leads to stroke brain injury. Exp Neurol. 2021;345:113827.
  2. Yuan D, Liu C, Wu J, Hu B. Nest-building activity as a reproducible and long-term stroke deficit test in a mouse model of stroke. Brain Behav. 2018;8(6):e00993.
  3. Yuan D, Liu C, Hu B. Dysfunction of Membrane Trafficking Leads to Ischemia-Reperfusion Injury After Transient Cerebral Ischemia. Transl Stroke Res. 2018;9(3):215-22.
  4. Liu C, Gao Y, Barrett J, Hu B. Autophagy and protein aggregation after brain ischemia. J Neurochem. 2010;115(1):68-78.
  5. Ge P, Luo Y, Liu CL, Hu B. Protein aggregation and proteasome dysfunction after brain ischemia. Stroke. 2007;38(12):3230-6.
  6. Zhang F, Liu CL, Hu BR. Irreversible aggregation of protein synthesis machinery after focal brain ischemia. J Neurochem. 2006;98(1):102-12.
  7. Liu CL, Ge P, Zhang F, Hu BR. Co-translational protein aggregation after transient cerebral ischemia. Neuroscience. 2005;134(4):1273-84.
  8. Hu BR, Janelidze S, Ginsberg MD, Busto R, Perez-Pinzon M, Sick TJ, et al. Protein aggregation after focal brain ischemia and reperfusion. J Cereb Blood Flow Metab. 2001;21(7):865-75.
  9. Hu BR, Janelidze S, Ginsberg MD, Busto R, Perez-Pinzon M, Sick TJ, et al. Protein aggregation after focal brain ischemia and reperfusion. J Cereb Blood Flow Metab. 2001;21(7):865-75.
  10. Hu BR, Martone ME, Jones YZ, Liu CL. Protein aggregation after transient cerebral ischemia. J Neurosci. 2000;20(9):3191-9.

Meet Our Team

  • Bingren Hu, PhD, MD

    Bingren Hu, PhD, MD

  • Chunli Liu, PhD

    Chunli Liu, PhD

  • David Berry

    David Berry

  • Yamileck Olivas-Garcia

    Yamileck Olivas-Garcia

Example Project

One of the current working hypotheses in the lab is that the inactivation of a key membrane trafficking protein called N-ethylmaleimide sensitive factor (NSF) leads to release of cathepsin B, contributing to stroke brain injury.

Figure Legend: Schematic of NSF inactivation and CTSB Release after Stroke. Upper: In sham neurons, lysosomal hydrolytic enzymes and lysosomal structural proteins are synthesized on the ER-associated polyribosomes, modified in the ER and the Golgi lumen, and transported via vesicles to the late endosome (LE). LEs also receive waste cargos from early endosome (EE) of the endocytic pathway and autophagosome (AP) of the autophagic pathway. The enzyme- and waste cargo-loaded LEs then enter the “Endolysosomal Cycle” to fuse with acidic terminal lysosomes (L) to form an endolysosomes (EL) where cargo can be degraded in an acidic environment (~pH 4.5). After cargo degradation, ELs convert into new Ls via NSF-mediated mechanism to repeat the LE-to-L fusion cycle. Lower: After stroke, MCAO leads to NSF inactivation in neurons, thus causing disruption of the EL’s conversion to a new L. This causes endocytic and autophagic pathway backups. Consequently, increasing the size and number of all related structures before the EL to L conversion phase. The cascade damages CTSB-containing structures, releasing CTSB into the cytoplasm and extracellular space, contributing to brain injury after stroke.