Interim Dow Chair of Neurology & Director of Neurobiology Research 
Director of Basic and Translational Research
Telephone: 503-413-1754
Fax: 503-413-5465
Email: dboison@downeurobiology.org
Detlev Boison obtained his Ph.D. in Biochemistry from the University of Cologne, Germany. Before joining the R.S. Dow Neurobiology Laboratories in 2005, he headed a research group at the University of Zurich, Switzerland, where he obtained his Habilitation (venia legendi) in cellular pharmacology.
The Boison lab:
Back Row, left to right: Haiying Shen, Kiran Akula, Wes Plinke, Detlev Boison*, Philipp Singer, Theresa Lusardi, Zhongya Wang, Gene Eysmont, Sylvain Dubroqua and Ben Yee. Front Row, left to right: Marissa Hanthorn, Shayla Coffman, Ursula Sandau, Martine Emond, Letisha Wyatt, Deepti Lall, and Yan Zhao
Co-Investigator
Benjamin Yee, DPhil
Senior Research Associate:
Haiying Shen, MD, PhD
Research Associates:
Theresa Lusardi, PhD
Ursula Sandau, PhD
Postdoctoral Fellows:
Kiran Kumar Akula, PhD
Sylvain Dubroqua, PhD
Philipp Singer, PhD
Zhongya Wang, PhD
Martine Pascale Emond, PhD
Deepti Lall, PhD
Letisha Wyatt, PhD
Research Assistants
Shayla Coffman
Marissa Hanthorn
Wesley Plinke
Research Student
Gene Eysmont
Research Scholar
Yan Zhao
Research Interests
The focus of my work is the brain’s endogenous anticonvulsant and neuroprotectant adenosine. We try to understand how adenosine function and dysfunction contributes to normal and pathological brain function, respectively, and to translate these findings into novel therapeutic approaches. We study adenosine-related physiological and pathophysiological mechanisms in rodent models of disease and in mice with engineered mutations in adenosine metabolism or signaling. Bioengineered polymers, stem cell therapies, and gene therapies are used to afford therapeutic augmentation of the adenosine system. We apply these tools to study disease mechanisms and treatment options in epilepsy, traumatic brain injury, stroke, and schizophrenia.
The Adenosine Kinase Hypothesis of Epileptogenesis
Research from several laboratories suggests that epilepsy is a disease of astrocyte dysfunction and challenges the neurocentric dogma in epilepsy research. Identification of the astrocyte as a new therapeutic target for epilepsy therapy is important, since current antiepileptic drugs, that all act by modifying the function of neurons, fail in about one third of all patients with epilepsy. The brain of individuals who suffer from epilepsy is characterized by astrogliosis. Little is known about the mechanisms that link astrogliosis to neuronal dysfunction, but it is hoped that identifying these mechanisms could lead to new possibilities for therapeutic intervention. Using a mouse model of focal epileptogenesis whereby injection of the chemical kainic acid (KA) into the amygdala restricts astrogliosis and epileptogenesis to the CA3 region of the hippocampus, we have shown that adenosine kinase (ADK) expressed by astrocytes is a key molecular link between astrogliosis and neuronal dysfunction. Expression of ADK was shown to be upregulated only in the CA3, and spontaneous focal electroencephalographic seizures were also restricted to this region of the brain. Consistent with a central role for ADK in neuronal dysfunction, transgenic expression of ADK in the CA3 induced spontaneous seizures in this region of the brain, and mice in which expression of ADK was reduced in the forebrain were resistant to KA-induced epileptogenesis. Furthermore, ADK-deficient ES cell-derived neural progenitor grafts suppressed astrogliosis, ADK upregulation, and seizures when implanted after KA administration. We therefore suggest that increased expression of ADK might predict epileptogenesis and that ADK-based therapeutic strategies might provide a new approach for the treatment of individuals with epilepsy. These findings have been published in the Journal of Clinical Investigation and in Progress of Neurobiology and can be accessed here:
Adenosine kinase is a target for the prediction and prevention of epileptogenesis in mice
The adenosine kinase hypothesis of epileptogenesis
Focal Adenosine-Augmentation Therapies to Treat Epilepsy
Research from our lab has demonstrated that deficiencies in the brain's own adenosine-based seizure control system contribute to seizure generation. Consequently, reconstitution of adenosinergic neuromodulation constitutes a rational approach for seizure control. Therefore, focal adenosine augmentation therapies (AATs) have significant potential for antiepileptic and disease modifying therapy. Due to systemic side effects of adenosine focal adenosine augmentation - ideally targeted to an epileptic focus - becomes a therapeutic necessity. This has experimentally been achieved in kindled seizure models as well as in post status epilepticus models of spontaneous recurrent seizures using four different therapeutic strategies: (i) Polymer-based brain implants that were loaded with adenosine; (ii) Brain implants comprised of cells engineered to release adenosine and embedded in a cell-encapsulation device; (iii) Direct transplantation of stem cells engineered to release adenosine; and (iv) Knockdown of ADK in vivo using viral gene therapy vectors. To meet the therapeutic goal of focal adenosine augmentation, genetic disruption of the adenosine metabolizing enzyme adenosine kinase (ADK) in rodent and human cells in vitro (ex vivo gene therapy) or directly in vivo (in vivo gene therapy) was used as a molecular strategy to induce focal adenosine augmentation, which demonstrated potent antiepileptic and neuroprotective properties. Examples of AATs have been published in Brain and in Experimental Neurology and can be found here:
Lentiviral RNAi-induced downregulation of adenosine kinase in human mesenchymal stem cell grafts: a novel perspective for seizure control.
Suppression of kindling epileptogenesis by adenosine releasing stem cell-derived brain implants.
The adenosine hypothesis of schizophrenia
Schizophrenia (SZ) is a debilitating mental illness with tremendous human, social and financial costs to society. Unfortunately, existing treatments are unsatisfactory and current development remains stagnant due to poor understanding of the biological bases of the disease. Two perspectives have emphasized disturbances in two neurochemical messengers in the brain -dopamine and glutamate, in relation to disparate SZ- symptoms. In our studies we examine a third messenger -adenosine, as a potential link uniting the dopamine and glutamate hypotheses of SZ. Adenosine can regulate both dopamine and glutamate neurotransmission via receptors with opposing actions (A1 vs. A2A adenosine receptors). Adenosine is therefore uniquely positioned as an upstream coordinator/regulator between these two neurotransmitter systems. Hence, adenosine-based treatment may be an attractive alternative with dual corrective actions on the glutamate and dopamine systems, thereby achieving effective control over selected SZ symptoms. Our central hypothesis is that subtle disturbances in adenosinergic neuromodulation can give rise to selected behavioral endophenotypes implicated in SZ; thus corresponding corrective interventions targeting at the ADO system should confer therapeutic potential against such SZ endophenotypes, and thereby validate our hypothesis.
The abstract for a related publication can be found here: Transgenic overexpression of adenosine kinase in brain leads to multiple learning impairments and altered sensitivity to psychomimetic drugs.
See also: