OHSU

Mary Stenzel-Poore

The Stenzel-Poore research program centers on the interplay between neuroprotection and ischemic injury and how the immune system regulates these processes. The lab integrates both a discovery and translational approach to research, working to speed the development of therapeutics from the bench to the bedside. Our discovery based research focuses on the molecular mechanisms of brain injury and protection using systems biology approaches. Through the use of in vitro and in vivo mouse models of ischemia, we have shown that activation of Toll-like receptors (TLR), a family of innate immune receptors, prior to an ischemic event provides significant protection against brain injury. We have discovered that this pretreatment (i.e. preconditioning) reprograms the response to ischemia to produce an endogenous neuroprotective transcriptomic signature that depends on interferon-associated genes. We are developing these TLR agonists for use as neuroprotectants through our translational research program that tests promising agents in our novel non-human primate model of stroke. Importantly, we have shown that preconditioning with a TLR9 agonist, CpG oligonucleotides, substantially protects rhesus macaques against a subsequent cerebrovascular ischemic event, demonstrated by both a reduction in infarct size and neurological deficit. These findings have enabled us to initiate IND studies in preparation for Phase I clinical trials with human patients. These studies are supported through efforts of an expert stroke team of multi-disciplinary investigators who bring state of the art competencies in basic research, neurosurgery, primate behavior, multi-modal imaging, drug testing feasibility studies and biomarker development.

 

BIOGRAPHY

 

Mary Stenzel-Poore is Professor and Chair of the Department of Molecular Microbiology and Immunology (MMI) at Oregon Health & Science University (OHSU). She received her PhD in Immunology from OHSU in 1986. She was a postdoctoral fellow at the Salk Institute in San Diego prior to joining the Department of MMI at OHSU as an Assistant Professor in 1995. In 2009 Dr. Stenzel-Poore was appointed chair of MMI and Associate Dean for Basic Sciences at OHSU. She was appointed as the Senior Associate Dean for Research in the School of Medicine at OHSU in 2012. 

 

KEY PUBLICATIONS

 

Packard AEB, Hedges JC, Bahjat FR, Stevens SL, Conlin MJ, Salazar AM, Stenzel-Poore MP. (2012) Poly-IC preconditioning protects against cerebral and renal ischemia-reperfusion injury. Journal of Cerebral Blood Flow & Metabolism. 32(2):242-247. PMCID: PMC3272611.

Bahjat FR, Williams-Karnesky RL, Kohama SG, West GA, Doyle KP, Spector MD, Hobbs TR, Stenzel-Poore MP. (2011) Proof of concept: pharmacological preconditioning with a Toll-like receptor agonist protects against cerebrovascular injury in a primate model of stroke. Journal of Cerebral Blood Flow & Metabolism.  31(5):1229-42. PMCID: PMC3099644. 

Stevens SL, Leung PY, Vartanian KB, Gopalan B, Yang T, Simon RP, Stenzel-Poore MP. (2011) Multiple preconditioning paradigms converge on interferon regulatory factor dependent signaling to promote tolerance to ischemic brain injury. Journal of Neuroscience. 31(23): 8456-63. PMCID: PMC3130521.

Vartanian KB, Stevens SL, March BJ, Williams-Karnesky R, Lessov NS, Stenzel-Poore MP. (2011) LPS preconditioning redirects TLR signaling following stroke: TRIF-IRF3 plays a seminal role in mediating tolerance to ischemic injury. Journal of Neuroinflammation. 8:140. doi:10.1186/1742-2094-8-140. PMCID: PMC3217906.

 

See a full listing of Dr. Stenzel-Poore's publications.