Team Members
Research Team
Principal Investigator
Colleen Niswender, Ph.D.
Associate Professor of Pharmacology
Warren Director of Molecular Pharmacology, WCNDD
Research Faculty
Shalini Dogra, Ph.D.
Research Instructor of Pharmacology
My research elucidates the molecular mechanisms of neurotransmission to identify and validate novel therapeutic targets for treating psychiatric disorders including schizophrenia and mood disorders. I am primarily focused on evaluating brain circuitry-specific changes observed in disease states and then determining the mechanisms whereby metabotropic glutamate receptors regulate various brain circuits using state-of-the-art approaches like slice electrophysiology, optogenetics, fiber photometry and in vivo behavioral pharmacology. My goal is to decipher and validate the utility of compounds targeting these receptors as potential therapies for treating neuropsychiatric disorders.
Alice Rodriguez, Ph.D.
Research Instructor of Pharmacology
My current research is focused on the metabotropic glutamate receptor and cannabinoid receptor allosteric modulator drug discovery programs. I work closely with others in the molecular pharmacology and chemistry groups to develop positive and negative modulators of mGlu and CB receptors for use as therapeutic agents for disease states such as depression, anxiety, and schizophrenia. My mGlu work is centered on the group III mGlu receptors, including mGlu7 and mGlu8. mGlu7 is widely distributed in the CNS where mutations or deletions of the receptor result in symptoms of neurodevelopmental disorders such as Rett syndrome. Preclinical studies have suggested that modulators of mGlu8 may be beneficial in the treatment of various CNS disorders. We are currently developing new allosteric ligands that interact with and modulate group III mGlu receptors to better understand the involvement and therapeutic possibilities of these receptors. I am also involved in the development of CB2 PAMs as a new therapeutic approach for the treatment of schizophrenia and other CNS disorders. Our research provides insight into the complicated CB receptor pharmacology impacting new treatment strategies for brain disorders.
Postdoctoral Fellows
Kim Holter, Ph.D.
Postdoctoral Fellow
The primary role of my project is to evaluate the underlying physiological and therapeutic roles of mGlu1/5 heterodimers. Metabotropic glutamate receptors are obligate dimers and there is increasing evidence to support that they function not only as homodimers but also as heterodimers. However, while we know mGlu1/5 heterodimers exist, there is limited evidence for their underlying pharmacological and physiological roles. Fortunately, we have identified mGlu1 PAMs from the Warren Center for Neuroscience Drug Discovery that differ in their activity at mGlu1/5 heterodimers. I am continuing to characterize mGlu1 PAMs in vitro and using select compounds as tools to begin to understand on a physiological and therapeutic level what happens when you do vs do not potentiate the mGlu1/5 heterodimer.
Graduate Students
Tony Ferranti
Pharmacology Graduate Student
My project is focused on investigating the therapeutic potential of targeting metabotropic glutamate (mGlu) receptor heterodimers, specifically the mGlu7/8 heterodimer. While drug discovery efforts for mGlu receptors have traditionally focused on homodimers, emerging evidence suggests that mGlu heterodimers exhibit unique pharmacology and circuit-specific expression patterns in the brain to regulate neural plasticity. In particular, the mGlu7/8 heterodimer regulates long term potentiation on the hippocampus, which may underlie deficits in learning and memory deficits that present in neurodevelopmental disorders associated mGlu7/8 gene abnormalities, such as ADHD and epilepsy. My goal is to not only to demonstrate the precise physiological roles of the mGlu7/8 heterodimer to regulate hippocampal neural plasticity, but also to assess the molecular pharmacology of this target with small molecule allosteric modulators to generate more effective and safe treatment strategies for neurodevelopmental disorders.
Gigi Hunn
Pharmacology Gradudate Student
The goal of my project is to investigate potential treatments for Rett Syndrome, a rare neurodevelopmental disorder with severe cognitive and motor deficits. My focus will be to increase metabotropic glutamate receptor 7 expression in the brain by designing an antisense oligonucleotide that can block the binding of endogenous microRNAs, along with testing the effectiveness of positive allosteric modulators. I hope that these approaches will correct behavioral phenotypes in mouse models of Rett Syndrome.
Research Staff
Undergraduate Students
