Neuroscience Faculty

Research/Areas of Interest: My current interests are the physiology and pharmacology of channels belonging to the Cys-loop ligand-gated ion channel (LGIC) superfamily. These channels are associated with several neuropyschiatric disorders including epilepsy, anxiety, schizophrenia, depression, substance abuse and stroke. We use the patch-clamp technique to record and measure ion channel function of the following LGICs.

Research/Areas of Interest: The principal goal of my research is to understand how neurotransmission contributes to the function of neuronal networks. Neurotransmission is the most basic unit of neuronal communication. Disruption of the basic features of neurotransmission is associated with many neurological diseases. My lab aims to understand how specific properties of synaptic function contribute to network activity, and how changes in neurotransmission are involved in the pathology of disease states such as epilepsy and traumatic brain injury. We are specifically interested in astrocyte glutamate uptake, astrocyte/neuron interactions, GABAergic interneuron development, and metabolic control of neuronal activity. Using advanced neurotransmitter imaging, electrophysiological techniques, and more, my lab aims to answer questions about how neuronal network function is shaped by some of the most basic parameters of neurotransmission. We hope to contribute new understanding and novel therapies to treat epilepsy, traumatic brain injury, and other devastating neurological diseases.

Research/Areas of Interest: Alzheimer's disease (AD) accounts for approximately 70% of all cases of dementia. Currently, no cure or prevention for AD exists. During my predoctoral career, I conducted innovative studies on sporadic and familial AD mouse models aimed to elucidate the role of cerebellum in this pathology. Since I joined Dr. G. Tesco laboratory, I have been trying to comprehend the function of the protein GGA3 in both healthy and AD brains. I developed and advanced an innovative live cell imaging approach to investigate GGA3 trafficking in hippocampal neurons. I recently demonstrated that not only does GGA3 reside in axons, but fundamentally that this protein is essential for BACE1 trafficking regulation and homeostasis. Our current data demonstrate that GGA3 genetic deletion results in the accumulation of BACE1 in the axon of hippocampal neurons. Furthermore, we observed a general disruption of BACE1 axonal trafficking in GGA3 null neurons together with its accumulation in axonal swellings. We have also identified a novel AD-linked GGA3 loss of function mutation in late-onset AD patients. Altogether, our data demonstrate that GGA3 loss of function and consequent axonal accumulation of BACE1 initiate a cascade of events leading to AD-like axonopathy. Our studies provide a proof-of-concept that drugs aimed to preserve GGA3 function could be beneficial for AD treatment and/or prevention. Recently, I have been developing a new experimental approach to differentiate human neurons from iPSC derived from patient carrying familial AD mutations. I have already established a successful protocol to differentiate 2D iPSC-derived neuronal culture from these lines. Currently, I am collaborating with Dr. D. Kaplan to grow these neurons in silk-collagen protein scaffolds. This model is highly innovative. Differentiating neurons will grow in a donut-shaped porous silk sponge within an optically cleared collagen-filled central region which will allow, for the first time, live in vivo studies of a human Alzheimer's brain-like tissue during ageing under controlled experimental conditions.

Research/Areas of Interest: Research in the Maguire lab takes a systems physiology approach to studying the mechanisms contributing to neurological and neuropsychiatric diseases, with a focus on epilepsy and mood disorders. Our research has explored the impact of the neuroendocrine system on the comorbidity of epilepsy and depression as well as the role in postpartum depression. Working from the vantage point of synaptic changes, such as GABAergic dysregulation, to circuit dysfunction between the prefrontal cortex and the amygdala, to in vivo changes in excitability and behavior, we have explored many mechanistic levels contributing to neurological and neuropsychiatric diseases. We have incorporated cutting edge tools into our research program, where appropriate, to study the contribution of specific cell types and circuits in mediating physiological and pathological processes. Based on our discovery of neurosteroid-mediated alterations in GABAA receptor subunit expression during pregnancy and the postpartum period and our theory for a potential role in postpartum depression, a company designing neurosteroid-based treatment approaches embarked on a series of successful clinical trials for the treatment of postpartum depression. Our discoveries have also generated two useful mouse models of postpartum depression, leading to a collaboration with SAGE Therapeutics to perform preclinical studies on the underlying mechanisms and treatment options for postpartum depression. Our basic research program is also actively investigating the mechanisms of hypothalamic-pituitary-adrenal (HPA) axis regulation during the peripartum period and the contribution of dysregulation of the HPA axis in abnormal postpartum behaviors. Our research has also discovered a novel mechanism contributing to epilepsy progression and associated comorbidities, involving dysfunction in the regulation of the HPA axis. This work has carved out a niche in the field, establishing our lab as experts in this area. This work also earned two competitive research grants (RO1s) from the National Institutes of Health to fund this work. Our lab is presenting investigating the pathological consequences of seizure-induced activation of the HPA axis, focusing on the role of hypercortisolism in seizure susceptibility and associated comorbidities. Our research and technical expertise has led to collaborations with numerous faculty members within the Neuroscience Department at Tufts University School of Medicine (Steve Moss, Leon Reijmers, Maribel Rios), in other departments within the Tufts University School of Medicine (Carol Kumamoto, Larry Feig, Alain Charest), at Tufts University (Klaus Miczek), Tufts Medical Center (Jonas Galper, Julian Wu), and outside institutions (Bernard Luscher, Pennsylvania State University; Sue Paradis, Brandeis University).

Research/Areas of Interest: Research in my lab focuses on the receptors that mediate the actions of gamma-aminobutyric acid (GABA), the principal inhibitory neurotransmitter in the vertebrate nervous system. GABA receptors are also critical drug targets for anti-convulsants, sedatives and anesthetics. We are interested in understanding how neurons regulate the accumulation of these critical inhibitory receptors on the neuronal surface in addition to their functional properties. Given that altered GABA receptor function plays critical roles in a number of neuropsychiatric disorders, the results may lead to new insights and therapeutic strategies for such debilitating disorders as epilepsy, anxiety, schizophrenia, depression and substance abuse.