Current Research Directions
Dr. David Giovannucci:
Work in the Giovannucci lab uses a variety of electrophysiological, optical and biochemical methods to define the cellular and molecular mechanisms that underlie the cytosolic calcium dynamics that control salt, peptide and protein secretion. The exocytotic secretion of neuropeptide has profound consequences for neuronal function, cardiovascular homeostasis and GI tract regulation in health and disease. This work has significance for human health concerns such as GI cancer, hypertension and dry mouth. The lab also leads a multidisciplinary/multi-PI project advancing the use of biomarkers in saliva that correlate with neural stress, brain trauma and human performance. The Giovannucci lab has been continually supported by government, military, intramural or private grant funding.
Dr. Robert Smith
The Cognitive Disorders Research Laboratory (CDRL) is focused on asking and answering the largest possible questions in translational neuroscience. We combine proteomic, kinomic, and mechanistic approaches to study severe neuropsychiatric illnesses including schizophrenia, depression and autism spectrum disorders. Our recent work includes establishing bioenergetic dysfunction as a consequence of developing a brain with broken synapses. In a ground breaking series of experiments, we started with observations from postmortem brain samples, identified drugs using a novel bioinformatics work flow, and reversed cognitive defects in an animal model of cognitive dysfunction with a repurposed FDA approved drug.
Dr. John Wall:
The structural complexity of the adult human cerebral cortex is a subject of frequent astonishment. Equally astounding is the issue of how this complex structure is continuously maintained from week-week in an individual adult person. Cortical structure can change due to, e.g. learning and injury; however, from aging work on healthy adult groups it is currently thought that during week-week baseline living mature cortical structure is statically maintained. This static view of cortical maintenance had, surprisingly, never been directly tested in an individual person. Our human brain imaging group has recently used an unconventional longitudinal N-of-1 MRI design to study cortical structural maintenance by reiteratively sampling cortical thickness at regular week intervals over several months in an individual person. The results suggest cortical thickness undergoes continuously reversing incremental and decremental fluctuations over week and multi-week intervals.
This different view of cortical maintenance has provocative implications. One possibility is that ongoing thickness maintenance fluctuations reflect homeostatic maintenance of brain structure which, in turn, is related to broader systemic homeostatic maintenance of the body. Given the current view of brain maintenance, where brain structure is statically maintained over short intervals, there has been no reason to consider this possibility. We are exploring this issue by continuous tracking of cortical maintenance fluctuations and concurrent variations in systemic metabolic and other factors associated with body maintenance, to test for relationships between maintenance of the body and brain structure at an individual person level. This work has potential applications for understanding individual specific brain/body maintenance interactions that are of interest for developing N-of-1 precision medicine thinking.
Dr. Ipe Ninan:
Our studies over the last 10 years have been focused on how environmental, genetic and developmental factors influence the fear circuitry. We have demonstrated the synaptic mechanisms underlying the effect of a common single nucleotide polymorphism in the BDNF gene, the BDNF Val66Met, on cognitive and anxiety-related behaviors. Consistently, our studies have also demonstrated the key molecular mechanisms by which BDNF or the lack thereof modulates synapses. Another major interest of my lab has been understanding how fear expression is altered during adolescence. Our research has revealed a diminished plasticity and an altered somatostatin interneuron-mediated inhibition in the adolescent medial prefrontal cortex, a brain region critical for fear extinction. Despite the progress in our understanding of the synaptic and circuit mechanisms involved in fear regulation, little is known about the mechanisms underlying the resistance to extinguishing fear memory. This forced us to think beyond the classical fear circuitry. Consistent with the recently suggested role of the medial habenula-interpeduncular nucleas pathway in aversive behaviors, we have uncovered previously unknown synaptic plasticity mechanism in the medial habenula-interpeduncular nucleus pathway as well as their role in fear memory. Given that the medial habenula-interpeduncular nucleus pathway in upstream of the median raphe nucleus, which regulates fear memory expression, we are interested in understanding the role of the medial habenula-interpeduncular nucleus-median raphe pathway in fear regulation. Apart from the traditional electrophysiological and fear beavior paradigms, we employ optogenetic and pharmacogentic apporoached to elucidate the involvement of this pathway in fear regulation.