Johns Hopkins University

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The multidisciplinary research team includes faculty from the Departments of Anesthesiology and Critical Care Medicine, Neurology, and Radiology and the Institute of Cell Engineering at the Johns Hopkins University School of Medicine. The team is led by Dr. Raymond Koehler, who has 30 years of experience in performing preclinical neuroprotection studies of stroke. Drs. Valina and Ted Dawson are neuroscientists who bring expertise in neuronal cell death signaling pathways involved in excitotoxicity, stroke, and Parkinson’s Disease. Dr. Steve Zeiler is a stroke clinician with preclinical research expertise in testing motor function recovery after stroke in mice. Drs. Peter Van Zijl and Jiadi Xu are MRI scientists with extensive experience in developing new modalities of brain imaging for use in stroke and other neurological disorders. Furthermore, the team has a long history of collaborating together on experimental stroke projects funded by the NIH.


Publications Related to PARP and Stroke at JHU

1.    Eliasson MJL, Sampei K, Mandir AS, Hurn PD, Traystman RJ, Bao J, Pieper A, Wang ZQ, Dawson TM, Snyder SH, Dawson VL. Poly(ADP-ribose) polymerase gene disruption renders mice resistant to cerebral ischemia. Nature Med. 1997;3:1089-1095. doi 10.1038/nm1097-1089


2.    Goto S, Xue R, Sugo N, Sawada M, Poitras M, Johns DC, Dawson TM, Dawson VL, Crain BJ, Traystman RJ, Mori S, Hurn PD. Poly (ADP-ribose) polymerase (PARP-1) impairs early and long-term experimental stroke therapy. Stroke. 2002;33:1101-1106. doi 10.1161/01.str.0000014203.65693.1e


3.    Andrabi SA, Kim NS, Yu SW, Wang H, Koh DW, Sasaki M, Klaus JA, Otsuka T, Zhang Z, Koehler RC, Hurn PD, Poirier GG, Dawson VL, Dawson TM. Poly(ADP-ribose) (PAR) polymer is a death signal. Proc Natl Acad Sci USA. 2006;103:18308-18313. doi 10.1073/pnas.0606526103


4.    Li X, Nemoto M, Xu Z, Yu SW, Shimoji M, Andrabi SA, Haince JF, Poirier GG, Dawson TM, Dawson VL, Koehler RC. Influence of duration of focal cerebral ischemia and neuronal nitric oxide synthase on translocation of apoptosis-inducing factor to the nucleus. Neuroscience. 2007;144:56-65. doi 10.1016/j.neuroscience.2006.08.065.


5.    Li X, Klaus JA, Zhang J, Xu Z, Kibler KK, Andrabi SA, Rao K, Yang ZJ, Dawson TM, Dawson VL, Koehler RC. Contributions of poly(ADP-ribose) polymerase-1 and -2 to nuclear translocation of apoptosis-inducing factor and injury from focal cerebral ischemia. J Neurochem. 2010;113:1012-1022. doi 10.1111/j.1471-4159.2010.06667.


6.    Wang Y, Kim NS, Haince JF, Kang HC, David KK, Andrabi SA, Poirier GG, Dawson VL, Dawson TM. Poly(ADP-ribose) (PAR) binding to apoptosis-inducing factor is critical for PAR polymerase-1-dependent cell death (parthanatos). Sci Signal. 2011;4:ra20. doi 10.1126/scisignal.2000902.


7.    Andrabi SA, Kang HC, Haince JF, Lee YI, Zhang J, Chi Z, West AB, Koehler RC, Poirier GG, Dawson TM, Dawson VL. Iduna protects the brain from glutamate excitotoxicity and stroke by interfering with poly(ADP-ribose) polymer-induced cell death. Nat Med. 2011;17:692-699. doi 10.1038/nm.2387.


8.    Andrabi SA, Umanah GK, Chang C, Stevens DA, Karuppagounder SS, Gagné JP, Poirier GG, Dawson VL, Dawson TM. Poly(ADP-ribose) polymerase-dependent energy depletion occurs through inhibition of glycolysis. Proc Natl Acad Sci U S A. 2014;111(28):10209-14. PMC4104885. doi: 10.1073/pnas.1405158111.


9.    Wang Y, An R, Umanah GK, Park H, Nambiar K, Eacker SM, Kim B, Bao L, Harraz MM, Chang C, Chen R, Wang JE, Kam TI, Jeong JS, Xie Z, Neifert S, Qian J, Andrabi SA, Blackshaw S, Zhu H, Song H, Ming GL, Dawson VL, Dawson TM. A nuclease that mediates cell death induced by DNA damage and poly(ADP-ribose) polymerase-1. Science. 2016;354. PMC5134926. doi 10.1126/science.aad6872


10.    Zhang J, Li X, Kwansa H, Kim YT, Yi L, Hong G, Andrabi SA, Dawson VL, Dawson TM, Koehler RC, Yang ZJ. Augmentation of poly(ADP-ribose) polymerase-dependent neuronal cell death by acidosis. J Cereb Blood Flow Metab. 2017;37:1982-1993. PMC5464694. doi 10.1177/0271678X16658491

Meet the Team

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Ray Koehler (PI) 
Experimental stroke 
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Valina Dawson (co-I) 
Cell death pathways
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Ted Dawson (co-I)  
Neurodegeneration
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Steve Zeiler (co-I) 
Stroke motor recovery
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Peter Van Zijl (co-I) 
MRI 
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Steve Lannan
Neurobehavior
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Senthil Karuppagounder
Pharmacology
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Jian Liang
Experimental stroke
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Jiadi Xu
MRI
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Adnan Bibic
MRI