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Detlev Boison Ph.D.

Dow Chair of Neurology & Director of Neurobiology Research boison
Director of Basic and Translational Research
Telephone: 503-413-1754
Fax: 503-413-5465

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:

Boison Lab Photo 2017

Left to Right
Front Row: Valerie Huang, Emily Swinth, Sadie Krahn, Nandita Kumar, Adriana Rocha, Rkia El-Kharrag, Naly Setthavongsack, Bahar Shamloo
Middle Row: Amogh Pradeep, Hoda Gebril, Ariel Weingarten, Traci Plumb, Keshara Bandara, Haiying Shen, Serene Perkins 
Back Row:
Jake Vander Velden, Jesica Reemmer, Landen Weltha, Danielle Osborne, Randy Owen, Detlev Boison, John Ost


Senior Research Associate:
Haiying Shen, MD, PhD 

Research Associates:        
Danielle Osborne, PhD
Traci Plumb, PhD

Postdoctoral Fellows:
Rkia El-Kharrag, PhD
Hoda Gebril, PhD
Adriana Rocha, PhD
Bahar, Shamloo, PhD

Research Lead:
Jessica Reemmer

Research Assistants:

Nandita Kumar
Shayla (Tien) Sorensen
Randy Owen
Jake Vandervelden
Ariel Weingarten
Landen Weltha

Volunteers (Summer 2017):
Amogh Pradeep
Emily Swinth

Wheeler Foundation Students (Summer 2017):
Valerie Huang
Naly Setthavongsack

Research Program

The focus of my work is the brain’s endogenous anticonvulsant and neuroprotectant adenosine, which is a key homeostatic bioenergetic network regulator coupling receptor-mediated signaling pathways with epigenetic functions and mitochondrial bioenergetics. 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. In addition to adenosine, we study the neuromodulatory role of glycine in the hippocampus within the context of epilepsy and schizophrenia. My research program is summarized in the following graphic and detailed below:

Boison Lab Graphic


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:

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:

The Role of Adenosine Kinase in Traumatic Brain Injury
Approximately 30% of all epilepsies are symptomatic and traumatic brain injury (TBI) is estimated to cause 20% of all symptomatic epilepsies. Thus, it is estimated that in the United States, at least 0.5 million surviving individuals live with posttraumatic epilepsy (PTE). Increased extracellular adenosine as an acute response to brain injury is known to provide seizure suppression and neuroprotection. However, astrogliosis associated with acute injury results in increased adenosine kinase (ADK), the key regulator of ambient adenosine levels. Upregulation of the astroglial based kinase ADK leads to deficits in the adenosinergic inhibitory feedback-system and thus promotes seizures. Astrogliosis is not only a hallmark of many types of epilepsy, but also a consequence of TBI. Since TBI can lead to subsequent epileptogenesis, it is important to understand how astrogliosis may contribute to epileptogenesis. We aim to investigate how ADK is regulated in response to TBI and how these findings can be translated into applications to prevent epileptogenesis. The rationale for these studies is derived from the following previous findings from our lab: (1) Deficits of the adenosinergic system, in particular upregulation of ADK during astrogliosis, contribute to epileptogenesis and seizures. (2) Pharmacological blockade or RNAi-mediated downregulation of ADK effectively suppress seizures.

Adenosine kinase as therapeutic target in stroke
Acute brain injury can result in neuroprotection and tolerance to subsequent injury. However, the mechanisms of this endogenous neuroprotection are incompletely known. As the increase in adenosine following acute seizures is both neuroprotective and antiepileptic, adenosine may also provide neuroprotection and tolerance in ischemia. The elevation of adenosine following acute seizures is due to downregulation of adenosine kinase (ADK), the key enzyme of adenosine metabolism. Thus, the adenosine- ADK system may be a candidate as an endogenous tolerance effector. We investigate how ADK is regulated in response to ischemic brain injury and how these findings can be translated into applications to prevent damage to the injured brain. The rationale for these studies is derived from the following previous findings from our lab: (1) ADK is rapidly and transiently downregulated as an acute response to both injurious seizures and transient focal cerebral ischemia. (2) Upregulation of ADK renders the brain more vulnerable to ischemic cell loss. (3) Intrastriatal implants of adenosine releasing stem cells protect the brain from subsequent ischemia. (4) Pharmacological blockade or RNAi-mediated downregulation of ADK effectively suppress seizures and seizure-induced injury. Our most recent publication can be accessed here:

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. Our key hypothesis has recently been published in The Journal of Clinical Investigation

The interface of diet, energy homeostasis, and brain bioenergetics
A ketogenic diet (KD) is an alternative metabolic treatment for epilepsy, and multiple retrospective and prospective studies confirm its clinical benefits. The KD’s high-fat low-carbohydrate composition forces ketone-based rather than glucose-based metabolism, but it is not known how this shift leads to anticonvulsant consequences. Primary applications of KD therapy include pediatric and medically refractory epilepsy; its use is increasing globally, and clinical benefits are similar across cultures and age groups. Despite its success, side effects and requisite strict compliance have limited widespread use of KDs, and a diet-based approach is often considered as a last resort. By better understanding the mechanisms involved in the anticonvulsant actions of a KD, pharmacological strategies might be developed that take advantage of beneficial aspects and limit problems associated with diet therapy. Adenosine acting at adenosine A1 receptors (A1Rs) is a logical candidate for the effects of KD therapy. Adenosine is well-established as a powerful anticonvulsant, and endogenous adenosine acting at A1Rs is an important seizure-control mechanism; deletion of A1Rs or increased adenosine clearance by elevated adenosine kinase (ADK) both cause spontaneous intrahippocampal electrographic seizures and increase the brain’s susceptibility to injury. Conversely, therapeutic adenosine augmentation is highly effective in controlling seizures. Adenosine is the core of ATP, a key molecule in basic biochemistry, and a ligand at its own family of G protein-coupled cell-surface receptors. Thus, adenosine is a homeostatic bioenergetic network regulator involved in metabolism and ongoing neuronal activity, and well-positioned to translate metabolic changes into altered brain activity. Using three lines of transgenic mice that all exhibit electrographic seizures due to deficient adenosine signaling we present here the first direct evidence that adenosine acting at A1Rs contributes to the therapeutic effects of KDs. Our findings have been published in the July 2011 issue of the Journal of Clinical Investigation:

See also: