Scientific Review Committee

Sangram S. Sisodia, Ph.D.
The University of Chicago

Dr. Sangram Sisodia’s laboratory studies the molecular and cellular basis of Alzheimer's disease (AD), the most common cause of senile dementia. AD affects neurons in the neocortex, hippocampus and basal forebrain. Affected brain regions contain abundant levels of senile plaques composed of ß amyloid, derived from amyloid precursor proteins (APP).  Early-onset, familial forms of AD (FAD) are caused by inheritance of genes encoding mutant variants of presenilin 1 (PS1), presenilin 2 (PS2), and APP. Research in his laboratory has focused on understanding the normal biology of  PS1 and PS2, and the molecular and cellular mechanisms by which mutant PS and APP cause AD. To explore these issues, his laboratory has employed cellular and biochemical approaches, as well as transgenic and gene-targeted mouse models.  The mouse models have offered important insights into disease pathogenesis and his laboratory has discovered critical genetic and environmental factors that influence these processes.

Scott T. Brady, Ph.D.
University of Illinois at Chicago

The size and complex shapes of many neurons present unique challenges in delivering essential components to the right places in the right amounts. An efficient set of intracellular transport processes known as axonal transport are required to generate and maintain the functional architecture of neurons. Recent evidence suggests that many late onset neurodegenerative diseases, including Alzheimer’s, Huntington’s, and Parkinson’s disease, as well as ALS, are the result of disruptions in this trafficking of proteins essential for neuronal function. Remarkably, these often involve changes in the regulation of motor proteins and targeting of cargoes carried by axonal transport. Based on these approaches, Dr. Scott Brady’s lab is identifying novel pathogenic mechanisms and new therapeutic targets by studying these changes in neuronal transport mechanisms.

Michael D. Ehlers, M.D., Ph.D.
Duke University Medical Center

The research in the Ehlers Lab is focused at the interface of cell biology and neural circuit plasticity.  Our work is directed at understanding the organelles and mechanisms for protein trafficking and turnover in dendrites, and the relationship to synapse formation and function. The complex morphology of the neuron, with its elaborately branched dendrites onto which impinge hundreds to thousands of individual synapses, requires that highly specialized mechanisms exist for localizing, maintaining, and removing proteins at the synapse.  Such mechanisms are crucial for the initial establishment of postsynaptic specializations during synaptogenesis, and for activity-dependent changes in synaptic strength that underlie experience-dependent plasticity.  
Our work on the endocytic machinery of dendritic spines, the trafficking and regulation of glutamate receptors, and plasticity-induced remodeling of the postsynaptic membrane has provided new insight into compartmentalized membrane trafficking and signaling at synapses.  More recently, we have begun to examine the submicron organization of signaling complexes at the synapse as a basis for molecular information storage.
Using a combination of cutting-edge molecular techniques, high resolution live cell imaging, mouse genetics, and electrophysiology, we are actively pursuing three major lines of ongoing research in the lab.  First, we are using fluorescence and single molecule imaging together with genetic inactivation of single synapses to examine the nanoarchitecture and submicron surface mobility of receptors at glutamatergic synapses.  Second, we are developing and employing mouse genetic models for targeted electrical activation of genetically defined subsets of neurons.  With these models, we are probing the functional organization and plasticity of complex circuits including the mammalian olfactory system.  Third, we are working to determine how dendritic endosomes and localized endosomal membrane trafficking in spines controls the functional and structural plasticity of glutamatergic synapses during cellular paradigms of learning and memory.

Nicholas Hatsopoulos, Ph.D.
The University of Chicago

Dr. Nicholas Hatsopoulos’ research focuses on the neural basis of motor control and learning. He is investigating what features of motor behavior are encoded and how this information is represented in the collective activity of neuronal ensembles in the motor cortex. He is also interested in what way these representations change as motor learning occurs. To answer these questions, the electrical discharge of many motor cortical neurons is simultaneously recorded using multielectrode arrays and correlated with motor behavior. The encoding properties of individual motor cortical neurons are being studied to determine how these single cell properties relate to higher-order representations involving groups of neurons. The possibility that changes in functional connectivity among neurons may occur during motor learning is also being explored. Finally, various decoding strategies are being developed by which the activities of neural ensembles can be used to predict the behavior of the animal. Ultimately, this research may lead to neural prosthetic technologies that will allow people with spinal injuries or other severe motor disabilities to use brain signals to control either a cursor on a computer screen, a robot device, or even their own arm.

John A. Kessler, M.D.
Northwestern University

Dr. John Kessler’s laboratory focuses on the biology of embryonic stem cells and neural stem cells. He is interested in defining mechanisms regulating neuronal and glial differentiation of stem/progenitor cells, and on understanding how growth factors promote neuronal and glial survival and phenotypic expression. These studies seek to identify the cytokines that regulate stem cell proliferation and differentiation, to define the intracellular signals that transduce their effects, and to understand how the effects of different growth factors are integrated by the progenitor cell. Although the principal focus of these studies is on definition of mechanisms underlying stem cell differentiation, a significant effort is also devoted to applying molecular neurobiology to clinical problems. Specifically they are developing techniques for the treatment of spinal cord injury and stroke.

Jeffrey H. Kordower, Ph.D.
Rush University Medical Center

Dr. Jeffrey Kordower is a leading researcher in the fields of gene therapy, neural transplantation, nonhuman primate models of neurodegenerative disease and experimental therapeutic strategies for Parkinson’s and Huntington’s disease. In 1995, he made the pioneering demonstration that fetal transplants can survive in patients with Parkinson’s disease; a paper that was published in The New England Journal of Medicine. In 2000, he published the lead article in Science, demonstrating for the first time that gene delivery of a trophic factor called GDNF can prevent degeneration and restore function in nonhuman primate models of Parkinson’s disease. Dr. Kordower is a Scientific Advisory Board (SAB) Member for numerous biotechnology companies and foundations, including a founding member of the SAB for the Michael J. Fox Foundation. Currently his main interests involve gene therapy and cell replacement strategies using stem cells in rodent and nonhuman primate models of Parkinson’s and Huntington’s disease.

A. Kimberley McAllister, Ph.D.
University of California

Research in McAllister's laboratory focuses on understanding the cellular and molecular mechanisms of synapse formation, competition, and elimination in the developing visual cortex. The lab studies the formation, persistence, and elimination of individual synapses between dissociated, cultured visual cortical neurons using time-lapse imaging.
 
In addition to studying the cellular and molecular mechanisms of synapse formation and plasticity, her lab is also interested in elucidating the role for immune molecules in early postnatal cortical development. McAllister's lab is working to identify the role for cytokines and synaptic activity in regulating MHCI expression as well as detemrining the mechanisms that MHCI uses to negatively regulate cortical connectivity. Since these immune molecules are implicated in several neurodevelopmental disorders, including autism and schizophrenia, MHCI molecules could mediate the effects of the environment on cortical connectivity both during normal development and in neurodevelopmental disorders.

D. James Surmeier, Ph.D.
Northwestern University

The research in Dr. D. James Surmeier’s lab revolves around the question of how neuromodulators shape the excitability of basal ganglia neurons. The basal ganglia is a richly interconnected set of nuclei that regulates motor and cognitive behaviors. Disorders in basal ganglia function underlie a wide variety of psychomotor disorders including Parkinson's disease, dystonia, Huntington's disease, schizophrenia, and Tourette's syndrome. In many of these diseases, the principal defect appears to involve an alteration in dopaminergic signaling. For example, the symptoms of Parkinson's disease are a consequence of the death of dopaminergic neurons that innervate one of the basal ganglia nuclei, the striatum. Using a combination of optical, electrophysiological, and molecular approaches, Dr. Surmeier has made great strides in understanding the impact of neuromodulators, like dopamine, on basal ganglia function that will hopefully lead to new therapeutic strategies for diseases like Parkinson's disease.