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Research Programs of Excellence

Neuron

Shortly after its founding, the Iowa Neuroscience Institute funded five Research Programs of Excellence to focus collaborative efforts on key areas of research. The multidisciplinary teams, drawing together researchers from the traditional neuroscience disciplines of neurology, neurosurgery, psychiatry, and psychology, as well as biomedical engineers, computer scientists, and experts in brain imaging, genetics, and cell biology, were awarded $4 million from 2017-2022. In five years the teams collectively secured $89.2 million in external grant funding, published more than 350 scientific papers, and involved nearly 100 trainees in their research. 

In spring 2022, a second group of Research Programs of Excellence was selected from a competivite pool of proposals. These RPOEs will run from 2022-2025

Additionally, the Early-Stage Investigator Research Programs of Excellence support promising faculty researchers as they build their independent research careers.

Research Programs of Excellence 2022-2025

Schizophrenia

CerebellumThis team carries on the legacy of Nancy Andreasen, MD, PhD, in schizophrenia research with plans for collaborative, highly translational research to elucidate cerebellar mechanisms that contribute to schizophrenia pathophysiology, and to further develop cerebellar-targeted therapies. The researchers have already established a robust working group comprising cutting-edge brain imaging, electrophysiology, genetic and epigenetic research, circuit level mechanistic rodent studies, and neuromodulation-based therapy development. Together, they will push the boundaries of their individual labs, investigating the genetic and epigenetic factors that influence abnormalities including sleep oscillations and cognitive deficits.

Exceptional ability and autism: insights into cognitive divergence

This team seeks to identify the cognitive, neurobiological, and genetic basis of twice-exceptionality. Linked closely with the new Hawk-IDDRC, the project will expand knowledge about this critically underserved population and deepen understanding of the relationship between exceptional ability and psychiatric and neurodevelopmental disorders. The team concentrates expertise in neuroscience and gifted education to confront disparities in both scientific knowledge and available services for individuals with autism and exceptional intellectual ability.

 

Sleep, Mood, and Arousal in Alzheimer's disease and Lewy Body Dementia: Serotonin Hypothesis (SMASH)

Alzheimer’s disease and Lewy body dementia pose an ever-increasing public health concern as the population ages, affecting more than 6 million Americans. Both conditions are characterized by the accumulation of specific proteins in the brain. This team seeks to identify the anatomical origins of this protein buildup as well as clinical biomarkers of early-stage disease. Earlier diagnosis may enable interventions that slow or stop cognitive and memory impairments.

Neuroplasticity in the human brain: from molecules to circuits to systems

The human brain’s ability to undergo dynamic alterations in function, referred to as neuroplasticity, is essential for learning, memory, and recovery of function after injury or disease. This project brings together three teams of UI researchers who propose that functional recovery after a brain lesion relies on acute and chronic reorganization at sites that are in close proximity to the lesion and at sites that are remote but connected to the injured tissue. Controlling and enhancing neuroplasticity will facilitate better therapeutic strategies for individuals affected by neurological and psychiatric disorders.

2017-2022 Research Programs of Excellence

Neuromodulation

Led by Nandakumar Narayanan, MD, PhD, the goal of this RPOE was to solidify the interdisciplinary collaborations that will be integral to developing a leading translational neuromodulation research program at Iowa, and to develop and test new technology to deliver frequency-response adaptive brain stimulation. The team leveraged a wide array of techniques to record from the human and rodent brain, including EEG, single and multi-unit recordings, ensemble recordings, electrocorticography, and calcium imaging. They developed a considerable range of adaptive/closedloop technology, including new algorithms, and are still working towards adaptive stimulation. While this is a challenging problem, the momentum provided by this RPOE will continue through the many research careers, directions, and collaborations it has launched.

Bipolar Disorder

The Bipolar Disorder Research Program of Excellence, led by John Wemmie, MD, PhD, was founded on preliminary studies suggesting that patients with bipolar disorder exhibited abnormally acidic pH in the cerebellum compared to healthy control participants without bipolar disorder. The RPOE adopted a four-pronged approach to better understand the causes of this abnormality and its consequences. The approach included: 1) multimodal brain imaging, 2) cerebellum-targeted transcranial magnetic stimulation (TMS), 3) animal models, and 4) stem cells/genetic approaches. During the five-year funding period, the team reproduced the original observations of cerebellar abnormalities in bipolar disorder and extended them to learn that the abnormally acidic pH is related to disrupted metabolism in the cerebellum and altered functional and structural connectivity with forebrain circuits. The TMS studies confirmed that cerebellum-targeted TMS is safe, and it is sufficient to change functional connectivity between the cerebellum and forebrain emotional control sites. The animal studies suggest that the cerebellum is critical for communicating contingency errors to forebrain sites involved in mood and cognition and is thus likely to contribute to mood and cognitive symptoms central to the illness. The cellular studies have established in vitro conditions for culturing cerebellum-like neurons from patients, which will be critical in future studies for probing mechanisms underlying the apparent metabolic abnormalities. Finally, the genetic studies have confirmed elevated polygenic risk for bipolar disorder in the sample population, and have identified similarities between risk for bipolar disorder and that for other illnesses, including the white-matter inflammatory disease, multiple sclerosis. Overall, this work has substantially advanced understanding of the novel role the cerebellum in bipolar disorder.

Neuronal Ion Channels

The Composition and Trafficking of Neuronal Ion Channels Research Program of Excellence, led by Chris Ahern, PhD, investigated the molecular and genetic maintenance of electrical signaling, with a focus on sodium channel complexes. This work informs the development of new therapies for the treatment of diseases such as inherited and acquired pain disorders, epilepsy, amyotrophic lateral sclerosis and muscular dystrophy. The team made discoveries on the therapeutic potential for engineered transfer RNA (tRNA) molecules, taking a new direction in the identification of tRNA sequences that have the ability to repair premature termination codons associated with human disease. PTC mutations are considered to be “rare” mutations that are scattered across scores of human genes and broadly are a cause of intractable human disease. After working for almost 20 years already on similar “suppressor” tRNAs from other kingdoms of life, the RPOE support allowed the lab to expand this work to include human tRNA sequences. This work has proved to be foundational in spurring new investment and interest in tRNA for the treatment of human disease.

Mitochondrial Dynamics and Calcium Cycling

The Mitochondrial Dynamics and Calcium Cycling in Neuronal Injury, Excitability and Plasticity Research Program of Excellence, led by Stefan Strack, PhD, and Yuriy Usachev, PhD, used state-of-the-art imaging techniques and behavioral analysis in novel transgenic mouse models to learn more about the effects of mitochondrial dynamics and Ca2+ cycling in the brain at the molecular and cellular levels. The team explored how this information could be useful in developing therapies for neurodegenerative disease and epilepsy. The most significant conceptual advance of this RPOE is the identification of three proteins that influence mitochondrial form and function as potential drug targets for neurological disorders. In particular, the team identified two regulators of mitochondrial division/ fission, the division activator PP2A/Bβ2 and the fission inhibitor AKAP1/PKA, which may be promising targets for the treatment of peripheral neuropathy and cognitive decline, respectively.

Curing Heritable Blindness

The Science Behind Curing Heritable Blindness Research Program of Excellence, led by Val Sheffield, MD, PhD, and Ed Stone, MD, PhD, focused on the genetics and disease mechanisms underlying inherited blindness, seeking to translate discoveries into therapies including gene therapy, pharmaceuticals, and genome editing. Advancements toward this goal include the development of novel vectors for gene therapy, the use of induced pluripotent stem cells for developing retinal cells for treatment, and electromagnetic fields to reverse abnormal redox states associated with retinopathies.

Early Stage Investigator Awards

Marco Hefti, MD, & Elizabeth Newell, MD (2021-2023)

Developmental Insights into Alzheimer Disease Pathogenesis
Marco Hefti, MD, focuses on the developmental role of the tau protein and its relation to neurodegenerative tauopathies in human postmortem brain tissue, with the goal of identifying novel tau-targeted therapeutics for Alzheimer disease and other neurodegenerative tauopathies. His work represents a novel approach to understanding the pathogenesis of Alzheimer disease and related neurodegenerative tauopathies as an aberrant reactivation of developmental pathways regulating tau phosphorylation and aggregation.

Targeting the neuroimmune response following traumatic brain injury
Elizabeth Newell, MD, seeks to identify molecular mechanisms of traumatic brain injury (TBI) that may be targeted through the development of novel, precision therapies. She investigates the mechanisms by which neuroinflammation contributes to secondary injury following TBI, with a focus on age- and cell-specific mechanisms. She has developed a novel pediatric rodent TBI model to facilitate the study of age-dependent effects of neuroinflammation following severe TBI. 

Brian Dlouhy, MD, & Aislinn Williams, MD, PhD (2019-2021)

Understanding the amygdala’s role in controlling breathing
Brian Dlouhy, MDseeks to understand the mechanisms behind breathing impairment during and after seizures, a critical risk factor for sudden unexpected death in epilepsy - the most common cause of death in patients with chronic refractory epilepsy. His previous work found that when seizure activity spreads to the amygdala, it can induce apnea and oxygen desaturation. Using both animal models and human epilepsy patients, his work seeks to identify individuals at risk for sudden unexpected death in epilepsy, define the amygdala-brainstem pathway that causes seizure induced loss of breathing, and develop new circuit-based interventions with already approved drugs or novel neurosurgical techniques.

Voltage-gated calcium channels in developmental models of neuropsychiatric disease
Aislinn Williams, MD, PhDuses both animal and human models to study the mechanisms by which alterations in genes at the earliest stages of brain development increase risk for psychiatric disease, including bipolar disorder and schizophrenia. Her work aims to unravel how genes are changing during development and how these changes affect adult brain function. Identifying the developmental pathways involved in neuropsychiatric disease may lead to novel treatment targets.

Hanna Stevens, MD, PhD, & Jan Wessel, PhD (2017-2019)

Hanna Stevens, MD, PhD, studied how prenatal environmental factors, including maternal stress, environmental exposures, and genes affect early brain development, with the goal of understanding how these factors influence the risk of subsequent behavioral and psychiatric disorders.

Jan Wessel, PhD, investigated cognitive and motor control in health and disease with a view to understanding how motor and cognitive activity is optimally geared toward changing situational demands, and how age- and disease-related impairments to these functions can be alleviated.