Martha Constantine-Paton, Principal Investigator
Martha Constantine-Paton, a founding member of the McGovern Institute, is a professor in the Department of Brain and Cognitive Sciences, and also holds an appointment in the Department of Biology. She moved to MIT in 1999, having previously held professorships at Princeton University and later at Yale University, where she was director of the Interdepartmental Neuroscience Program. She is a past recipient of the Society for Neurscience Young Investigator Award and more recently a National Merit Award from the National Eye Institute.
Jian-Ping Zhao, Research scientist
Jian-Ping is interested in development regulation of glutamate receptor function. Using electrophysiological techniques and collaborating with molecular biologists, he is working on cellular and molecular mechanism on how NMDA receptors play a role in neural plasticity and neuropsychiatric disorders.
Akira Yoshii, Research scientist
Akira has been a member of the Constantine-Paton lab since completing a residency in pediatric neurology. He is interested in developmental regulation of postsynaptic density protein in the central visual system, specifically PSD-95 which is a scaffolding molecule at the glutamatergic synapse and the major regulator of synaptic plasticity. Akira has found that PSD-95 was redistributed to dendrites after eye-opening and is currently studying the role of BDNF/TrkB signaling in trafficking of PSD-95. Our findings suggest that BDNF facilitates pandendritic delivery of PSD-95 through PI3 kinase/Akt pathway which regulates ER to Golgi transport. Akira is also examining the role of MyosinVa in trafficking PSD-95 inside dendritic spines. In the long term, he would like to extrapolate his current work to dissect the pathophysiology of neurological disorders such as autism and epilepsy, also hoping to understand the neural correlates of language acquisition and sociability.
Yasunobu Murata, Postdoc
I'm interested in how glutamate receptors and their associating proteins function in activity-dependent visual circuit formation. Patterned vision through opened eyes induces rapid alternations in the postsynaptic protein composition, which underlie many synaptic changes observed shortly after eye-opening. Now my focus is on two postsynaptic scaffolding proteins; PSD-95 and SAP102, because visual synapses replace SAP102 with PSD-95 together with many other signaling and cytoskeletal molecules during development especially around the time of eye-opening. I'm analyzing roles of postsynaptic scaffolds in receptor trafficking and synapse formation in culture neurons using lentivirus-mediated gene transfer/knockdown, immunocytochemical and biochemical approaches. Also I'm looking at developmental changes of spine structure and synaptic connection in layer II/III visual cortical neurons with gene knockdown techniques, hopefully to see how visual activity and postsynaptic proteins work cooperatively to form the functional neuronal network.
Paula Feinberg-Zadek, Postdoc
Cansu Tunca, Graduate student
Cansu is studying mice with mutations in the MyosinVa gene. MyosinVa is a molecular motor involved in the transportation of vesicles along actin filaments within dendritic spines. Previous work in the lab has shown that trafficking of PSD-95 to the synapse is impaired in MyosinVa mutants. Cansu is currently testing the mutant's ability to induce long term potentiation (LTP) and long term depression (LTD) in hippocampal slices using field potential recording techniques. In addition, she is examining the morphology of CA1 pyramidal neurons in the hippocampus in the MyosinVa mutant.
Rory Kirchner, Graduate student
Andrew Bolton, Graduate student
As an undergraduate, Andrew's work focused on the relationship between genomic instability, nutrition, and schizophrenia. His current interests lie in the effects of the amino acid homocysteine (HCY), shown to be consistently upregulated in schizophrenia, on dopamine signaling and NMDA receptor function. Andrew is using patch clamp electrophysiology to determine the effects of homocysteine on recombinant NMDA receptors transfected into HEK293 cells. He is also interested in studying the synaptic scaffolding protein SAP-97, a MAGUK related to NMDA receptor trafficking and dopamine receptor scaffolding that has proven to be downregulated in the cortex of schizophrenia patients.
Beth Klein, Administrative Assistant
Fernanda Gubert, Graduate student
Fernanda is interested in studying amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disease that affects selectively the motor neurons. The loss of the motor neurons from the brain and spinal cord leads to a progressive muscle dysfunction and death in 3-5 years of onset. Until now there is no efficient treatment for ALS and the cause of this disease is still unclear. A transgenic ALS mouse model that over-expresses the human SOD1 gene was developed in order to study the disease mechanisms and some possible treatments. Fernanda intends to transplant mesenchymal stem cells (MSCs), which are present in the bone marrow, possess extensive proliferative potential, and have proven to be capable of migrating to injury sites and releasing growth factors like VEGF, into the brain of SOD1G93A mice. Because excitotoxicity has been implicated as an important mechanism during the progression of ALS, illustrated by a marked loss of glutamate transporter EAAT2 expression and function, EAAT2 will be injected along with the MSCs.