Matthew P. Anderson, M.D., Ph.D.
Department of Pathology
Department of Neurology
Harvard Medical School
Center for Life Sciences
Beth Israel Deaconess Medical Center
330 Brookline Avenue, E/CLS-709
Boston, MA 02215
Lab Website: The Anderson Lab
The Anderson Lab applies mouse genetics (Cre/loxP and BAC recombineering), protein biochemistry, and electrophysiology to study the basis of inherited neurological diseases, autism, and epilepsy. Gene copy number variations (CNV) were recently reported in autism. Maternal 15q11-13 duplication, the most common autism CNV, contains two genes with maternal allele-specific expression in neurons. We developed and are investigating murine models of this disorder focusing on glutamate synapse development and function. Many epilepsy disorders result from ion channel mutations. T-type calcium channel Cav3.2 (CACNA1H) is mutated in epilepsy disorder patients suggesting a role in seizure susceptibility. Interestingly, Cav3.2 increases in hippocampal CA1 pyramidal neurons in acquired temporal lobe epilepsy following status epilepticus. We developed and are investigating murine models of this inherited and acquired ion channelopathy. Selectively deleting T-type channel Cav3.1 in thalamus (Cre/loxP-targeted gene-deletion) disrupted burst firing and caused severe sleep fragmentation. This brain-mapped murine sleep disorder is also under investigation. Recent studies uncovered mutations in non-ion channel gene, leucine-rich glioma-inactivated 1 (LGI1). LGI1 co-purifies with pre-(potassium channel Kv1.1) and post- (PDS95) synaptic protein complexes, but the brain function of the epilepsy gene remains an enigma. We created mice with extra wild-type gene copies and with a truncated dominant negative gene mutant found in epilepsy patients. Preliminary results suggest a role in glutamate synapse development. Collaborative studies with Jeff Flier's lab investigate electrophysiological properties of newborn neurons formed in adult hypothalamus. Collaborative studies with Jeff Flier and Jeff Macklis investigate the functional integration of neural progenitors into the hypothalamus.
For a complete listing of all of Matthew Anderson's publications on PubMed, click here.