Laura Jansen, MD, PhD is a physician-scientist and a perfect example of how an individual with training as both a physician and neuroscientist can utilize that dual expertise to advance our knowledge of disease. Dr. Jansen, an Associate Professor of Neurology at the University of Virginia, is interested in developmental brain abnormalities and the ways in which those abnormalities lead to epilepsy.
As a pediatric neurologist, Dr. Jansen has clinical expertise in developmental brain malformations, many of which lead to epileptic seizures. As a neuroscientist, Dr. Jansen obtains human brain tissue specimens from diseased patients and studies the ways in which pathological changes in those specimens lead to epilepsy. Most of the brain samples are epilepsy surgery specimens obtained in the operating room during focal resections for the treatment of intractable epilepsy. Others are postmortem tissues that become available through tissue banks or through collaborations with other investigators.
Dr. Jansen’s strategy of applying basic science techniques to human tissues has great promise not only to increase our knowledge of neuroscience, but also to develop new therapies for the treatment of human brain disease.
Utilizing these tissue samples, Dr. Jansen brings basic science techniques to the study of human brain tissue. In the diseased tissues, she studies a host of diverse and important topics, including GABA receptor currents, pharmacologic responses, protein chemistry, gene sequences, antigen localization, and enzymatic activities.
Employing this strategy, Dr. Jansen has made important discoveries. In a project inspired by Dr. Sid Gospe, she found that antiquitin, the protein product of the ALDH7A1 gene that is mutated in pyridoxine-dependent epilepsy, is normally expressed in glial cells and that its dysfunction leads to neuronal migration abnormalities and other structural brain defects. These malformations likely explain the neurodevelopmental impairments that persist in pyridoxine-dependent epilepsy despite postnatal pyridoxine supplementation.
In collaboration with Drs. Bill Dobyns, Ghayda Mirzaa, and others at the University of Washington, Dr. Jansen has further found that mosaic mutations affecting a particular signaling pathway, the PI3K/AKT/mTOR pathway, can induce a spectrum of dysplastic brain malformations including megalencephaly, hemimegalencephaly, and focal cortical dysplasia. Which gene in the pathway is affected, which cells in the brain contain the mutation, and when in the course of development the mutation occurs all affect the specific pathologic outcome.
Dr. Jansen’s current project, funded by CURE (Citizens United for Research in Epilepsy), utilizes dysplastic human brain specimens to investigate whether agents that target the PI3K/AKT/mTOR pathway have therapeutic potential in the treatment of epilepsy. Thus, Dr. Jansen’s strategy of applying basic science techniques to human tissues has great promise not only to increase our knowledge of neuroscience, but also to develop new therapies for the treatment of human brain disease.
Functional, structural, and genetic studies of resected epileptic brain tissue.
A. FLAIR-weighted MRI from an infant with intractable epilepsy due to focal cortical dysplasia, seen as an area of increased cortical thickness, blurring of the grey-white junction, and abnormal white matter signal in the left occipital region.
B. Immunohistochemistry of cortex resected from patient in (A), showing dysmorphic neurons (orange) co-expressing MAP2 (green) and phospho-S6 (red).
C. In vitro AKT kinase assay results from frozen brain tissue.
D. GABA-A currents recorded from Xenopus oocytes incorporating receptors from resected cortex.
E. Sanger sequencing of genomic DNA isolated from epileptic cortex.
Editor’s Note: Some people claim that they have never met a person who is both very successful and very nice at the same time. Those people have clearly never met Laura Jansen. Dr. Jansen is an excellent physician-scientist, who is making substantial contributions to the field of child neurology. Laura is also a charming and witty person, who is very fun to talk to. Next time you’re at the CNS meeting, introduce yourself to Laura; she will inform you and brighten your day.