Nicole Baganz - Research Instructor
7144 MRB III
My primary research focus is on receptor and signaling pathways that regulate the expression and activity of the serotonin transporter (SERT). Serotonin (5-hydroxytryptamine, 5-HT) is an important neurotransmitter involved in controlling mood. Alterations in 5-HT neurotransmission are linked to neuropsychological disorders, such as depression. Extracellular levels of 5-HT are tightly controlled by the antidepressant-sensitive SERT. Pro-inflammatory cytokines, released in response to immune challenge and activation of the stress axis, can increase SERT activity and have been shown to generate depressive-like effects on behavior. Using genetic, biochemical, and behavioral approaches, I am using rodent models to investigate the role of IL1R/p38 MAPK signaling pathways in modulating SERT across the lifespan and in relation to autism and mood disorders. Editor's Note: Nicole is also a prolific writer, winning the nonfiction category in the 2011 House Organ writing competition and was the first Guest Writer for Scientific American's The Scicurious Brain Blog.
Maureen Hahn - Research Associate Professor
7160A MRB III
My research seeks to understand the neurotransmitter signaling pathways underlying emotional and cognitive processes, including mood, attention, reward, learning, memory, and stress response, and the neuropsychiatric disorders that can arise with disruption of these systems. Research focuses on neurotransmitter transporters that regulate the catecholamines, norepinephrine (NE) and dopamine (DA). The duration and intensity of NE and DA signaling in the brain (and additionally in the sympathetic autonomic nervous system in the case of NE) are limited by the presynaptically localized transporters for NE (NET) and DA (DAT) that clear released neurotransmitter through active transport into terminals. DAT and NET are both targets for psychostimulants, including those that treat attention-deficit hyperactivity disorder (ADHD). NET is also a target for tricyclic antidepressants, and NET-selective reuptake inhibitors (NSRIs), the latter also effectively treat ADHD. One focus of our research is to investigate genetic variation in the human NET and DAT genes and the consequences for transporter function, and contribution to psychiatric and cardiovascular disease. Transgenic mouse models allow for in vivo assessment of the effects of NET and DAT variants on catecholamine neuronal activity, physiology and behavior. Mouse projects include the study of the first NET knockin mouse (NET A457P), bearing a NET mutation identified in humans with postural orthostatic tachycardia. NET A457P mice recapitulate the NET deficiency observed in human carriers, and express cardiovascular and psychiatric-related phenotypes.
Hideki Iwamoto - Research Assistant Professor
7141 MRB III
Presynaptic neurotransmitter transporters play important roles in terminating the transmission and recycling of neurotransmitters. Perturbing neurotransmitter transporters by manipulating genes or administering drugs significantly alters neural activity. In many psychiatric disorders, neurotransmitter transporters can be altered and may contribute to the symptom of these disorders. My research involves the use of electrophysiological methods in combination with fluorescence imaging to assess the functional roles of neurotransmitter transporters on neural activity in brain slice and neuromuscular junction preparations.
Matt Robson - Postdoctoral Fellow
7144 MRB III
Serotonin is a crucial neurotransmitter engaged in multiple pathways in the CNS and periphery and is well known to play a key role in the central control of mood, cognition and certain aspects of brain development. Serotonin transporters (SERT) are presynaptic proteins that clear serotonin to aid in cessation of serotonergic signaling, as well as neurotransmitter recycling. Alterations in SERT activity are believed to be involved in the etiology of neuropsychiatric diseases such as depression and autism. Using transgenic animals, behavioral, and biochemical methods, I am working to determine how genetic changes and specific aspects of inflammation effect the regulation of SERT activity within the CNS. In the future, this work may help elucidate new protein and signaling targets for the production of novel pharmacotherapies aimed at treating neuropsychiatric disorders.
Osama Refai - Research Fellow
7144 MRB III
Serious diseases of the nervous system such as Parkinson’s disease, Schizophrenia and Attention Hyperactivity Disorder (ADHD) are associated with alterations in signaling by the neurotransmitter (DA). DA is used to modulate neural signaling in both vertebrates and invertebrates, including the nematode Caenorhabditis elegans. In the worm, as in man, a presynaptic DA transporter (DAT-1) constrains DA signaling by limiting extracellular DA availability. My research capitalizes on the power of the C. elegans model to identify and characterize genes that control DA signaling. Specifically, I use a combination of genetic, pharmacological and imaging approaches to elucidate mechanisms of DAT-1 regulation. The conservation of DAT-1 structure with vertebrate DAT proteins and the transporter’s powerful contribution to DA signaling and behavior in the nematode provides a key opportunity to discover elucidate novel molecules and mechanisms that may better reveal paths to treatments of human disorders associated with perturbed DA signaling.
Linda Simmler - Postdoctoral Fellow
7148 MRB III
My research focuses on the contributions of serotonin in the acute and chronic actions of cocaine. Cocaine abuse and addiction is a world-wide problem with a significant impact on physical and mental health and overall quality of life. The psychostimulant and rewarding actions of cocaine are well known to relate to the drug's blockade of dopamine transporters. However, cocaine blocks the serotonin and norepinephrine transporters with comparable potency, suggesting that the actions of these neurotransmitters contribute to important aspects of drug action. Using a transgenic mouse model that displays significantly reduced cocaine potency for blockade of the serotonin transporter (SERT Met172), I am elucidating the SERT and serotonin-dependent neuroadaptations that contribute to cocaine action. Hopefully, my research will improve our understanding of the molecular plasticities underlying cocaine action in the brain and lead to better treatments for cocaine addiction.
Adele Stewart - Postdoctoral Fellow
7150 MRB III
Perturbations in dopamine signaling contribute to multiple neuropsychiatric disorders including attention-deficit/hyperactivity disorder (ADHD), bipolar disorder (BPD), and autism spectrum disorder (ASD). The dopamine transporter (DAT) is a critical determinant of the magnitude and duration of dopamine signaling via its ability to facilitate reuptake of synaptic dopamine back into presynaptic nerve terminals. My research efforts focus on elucidating the functional biochemical and behavioral consequences of novel coding variants in the human DAT gene (SLC6A3) identified in patients diagnosed with ADHD, BPD, and/or ASD. In particular, I am involved in evaluating alterations in social and reward-related behaviors and the response to psychostimulants in a novel mouse model harboring the DAT A559V mutation. Additionally, I am characterizing a novel DAT mutant (E602G) identified in a patient with BPD. The overarching goal of my work is to provide insight into how alterations in dopamine transporter function or regulation contribute to neuropsychiatric illness.