NINDS Research Program Award (R35) Awardees

The first 30 recipients of the NINDS R35 Research Program Award are:

Katerina Akassoglou, Ph.D.
J. David Gladstone Institutes, California
Neurovascular interactions: mechanisms, imaging, therapeutic potential

Dr. Akassoglou’s research focuses on the interface between the brain and the immune and vascular systems, referred to as the blood-brain barrier (BBB). Alterations in the BBB occur in neurological conditions including stroke, multiple sclerosis, and brain and spinal cord injuries. By studying neurovascular interactions through varied and innovative methods, Dr. Akassoglou hopes to reveal disease mechanisms and identify new strategies for therapeutic development.

Allan I. Basbaum, Ph.D.
University of California, San Francisco
From the spinal cord to the brain: Neurology of the pain and itch neurons

Dr. Basbaum’s research centers on neural circuits that mediate pain and itch. Building on past research to establish how sensory messages are carried from the body to the spinal cord, future studies will take a multidisciplinary approach to understand how these messages are interpreted by the brain to produce varied pain and itch perceptions. These comprehensive analyses will inform new approaches to managing conditions that involve chronic pain and itch. 

Greg J. Bashaw, Ph.D.
University of Pennsylvania
Molecular mechanisms of axon guidance receptor regulation and signaling

Dr. Bashaw studies how different types of neurons develop and organize into functional circuits. His research program will investigate cellular signaling pathways that determine neuron type and that guide neuronal fibers called axons as they navigate to specific targets in the developing brain. Understanding the complexities of axon guidance signaling will yield important insights into neurodevelopmental disorders and strategies to repair neuronal connections after injury.

Nancy M. Bonini, Ph.D.
University of Pennsylvania
Molecular genetic insight into neurodegenerative disease from drosophila

Dr. Bonini’s research focuses on amyotrophic lateral sclerosis (ALS), a rapidly progressive motor neuron disease, and on frontotemporal dementia, the second most common form of dementia. She will apply a multidisciplinary approach spanning fruit fly disease models to patient-derived tissues to study biological pathways and risk factors that contribute to these diseases, and that may point to new avenues for treatment.

Manuel A. Castro-Alamancos, Ph.D.
Drexel University, Pennsylvania
Sensory pathways for stimulus detection during behavior

Dr. Castro-Alamancos conducts studies in rodent models to understand how neuronal circuits that process sensory information operate in different behavioral contexts, such as whether a sensory stimulus is new, familiar, or associated with a behaviorally relevant meaning. Understanding the basis for such differences is important for understanding normal behavior as well as conditions associated with impaired sensory processing.  

Edwin R. Chapman, Ph.D.
University of Wisconsin-Madison
Structure and dynamics of exocytotic fusion pores

The release of neurotransmitters at synapses, or the connections between neurons, is a fundamental process that is crucial for normal nervous system function. Dr. Chapman’s research applies novel methods to unresolved questions about the early steps in this process, in which vesicles containing neurotransmitters fuse with the releasing neuron’s cell membrane. Insights from this research may inform the development of treatments that work by altering neurotransmitter release.

Robert B. Darnell, M.D., Ph.D.
Rockefeller University, New York
Combining new molecular and informatic strategies to find hidden ways to treat brain disease

The human nervous system is composed of diverse cell types, each in turn representing a spectrum of subtypes with unique physical and functional properties. Dr. Darnell’s research program will use molecular and bioinformatic approaches to analyze RNA regulation (a key contributor to cellular diversity) in the human brain. Understanding this diversity will be critical for precision medicine approaches to treat the underlying causes of disease. 

Graeme W. Davis, Ph.D.
University of California, San Francisco
Homeostatic stabilization of neural function in health and disease

Changes in neural circuits that allow us to learn and adapt are known as neuronal plasticity. While essential for normal nervous system function, this plasticity must also be balanced by processes that stabilize overall neuronal activity. Such homeostatic stabilization is the focus of Dr. Graeme Davis’s research program, which will aid our understanding of disorders in which homeostatic mechanisms may be impaired, such as epilepsy, autism, and neurodegenerative diseases.  

Ronald L. Davis, Ph.D.
Scripps Research Institute, Florida
Biology of memory

Dr. Ronald Davis studies the molecular and cellular underpinnings of learning and memory. Using a variety of experimental models and methods, his research program will focus on brain mechanisms that mediate forgetting, how the brain organizes memories, and the roles of genes that suppress memory formation. This research will advance our understanding of how we learn and forget, as well as how these mechanisms are altered in disease.

Donna M. Ferriero, M.D.
University of California, San Francisco
Precision therapy for neonatal brain injury

Neonatal brain injury due to hypoxia-ischemia, or insufficient blood and oxygen flow, is an important cause of death and disability in children, including intellectual disability, epilepsy and cerebral palsy. Therapeutic hypothermia (TH) is the standard of care for hypoxic-ischemic (HI) brain injuries, but only 60% of babies respond to treatment. Dr. Ferriero aims to identify new therapeutic targets by defining the biological signatures of TH responders and non-responders.

David D. Ginty, Ph.D.
Harvard Medical School, Massachusetts
Elucidating cutaneous mechanosensory circuits, from development to disease

The first step leading to touch perception is activation of sensory neurons in the skin called low-threshold mechanoreceptors (LTMRs). Dr. Ginty uses genetic tools in mouse models to investigate the development and function of different types of LTMRs and how they organize into neural circuits in the spinal cord and brainstem. His research will also assess abnormalities in these circuits in animal models of autism and neuropathic pain.

Aaron D. Gitler, Ph.D.
Stanford University, California
Innovating yeast and human genetics approaches to define mechanisms of neurodegenerative disease

Dr. Gitler’s research focuses on disease mechanisms in amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Parkinson's disease. To expand on his past research using mainly yeast genetics, he will use genome-wide screening to identify genetic modifiers of disease in human cells and validate their function in neuronal cell cultures and mouse models. Findings from these studies may translate into new targeted treatments for neurodegenerative diseases.   

David H. Gutmann, M.D., Ph.D.
Washington University, Missouri
Defining the mechanistic basis for Neurofibromatosis-1 nervous system disease heterogeneity

Neurofibromatosis type 1 (NF1) is a rare genetic condition leading to cognitive and behavioral problems, low-grade brain tumors, and other symptoms that vary across affected individuals. Currently, there is no way to predict disease course or severity in an individual child with NF1. To address this challenge and inform precision-medicine strategies, Dr. Gutmann will study disease variability using patient-derived cells, genetic mouse models, and bioinformatics approaches.

Yuh-Nung Jan, Ph.D.
University of California, San Francisco
Dendrite morphogenesis, function and regeneration

Dr. Jan’s research focuses on the development and function of dendrites, neuronal fibers that typically serve as the receiving end for messages from other neurons. He will continue fundamental research to define how dendritic branching patterns are controlled, using the fruit fly nervous system as a model. Newer directions for Dr. Jan’s research program will include studies of dendrite regeneration after injury as well as mechanosensation in Drosophila sensory neurons.  

David Kleinfeld, Ph.D.
University of California, San Diego
Resilient versus fragile aspects of blood flow in the mammalian brain

Dr. Kleinfeld’s research is advancing our understanding of blood flow in the brain and how blood flow dynamics change after blockage (such as in stroke) and in response to neural activity. Using a range of behavioral, physiological, and imaging approaches, studies will define the vascular architecture in the hippocampus - a brain region that is highly sensitive to reduced blood flow, and investigate how patterns of flow are coordinated across the brain.

Arnold Kriegstein, M.D., Ph.D.
University of California, San Francisco
Development and expansion of the human cerebral cortex

Although research using model organisms has been instrumental to understanding brain development, such models cannot fully recapitulate complexities that are unique to the human brain. Dr. Kriegstein’s research program will address this challenge by studying developmental processes in human brain tissue and in cerebral organoids, a new experimental technique that grows cortex-like three-dimensional structures from human-derived stem cells.

Seok-Yong Lee, Ph.D.
Duke University, North Carolina
Structure, function, and pharmacology of neuronal membrane transport proteins

Membrane transport proteins, including neuronal ion channels, selectively transport certain types of molecules across the cell membrane, and this selectivity is critical for cellular signaling processes. Dr. Lee’s research seeks to explain the selectivity of membrane transport proteins through studies to define the structure and function of ion channels involved in pain and itch. Findings from this research will inform new strategies to modulate pain and itch signaling.

Eve E. Marder, Ph.D.
Brandeis University, Massachusetts
Neuromodulation and robustness of neurons and networks

Dr. Marder focuses on how neurons and neuronal networks maintain overall stability despite ongoing modulation, turnover of cellular components responsible for neuronal activity, and variability in the number of ways a given neuron or network might generate a desired activity pattern. Her research combines experimental and computational studies of a small circuit in crustaceans to yield fundamental insights relevant to understanding more complex neuronal circuits.

David A. McCormick, Ph.D.
Yale University, Connecticut
Cortical dynamics and neural/behavioral performance

Our arousal state affects our ability to detect and respond to sights, sounds, and other sensory information, which in turn influences how well we respond to or perform behavioral tasks. Dr. McCormick’s research program will employ state-of-the-art methods in animal models to understand the mechanisms through which arousal influences sensory processing in the brain, and to determine what parameters lead to optimal responses and behavioral performance.

Guo-Li Ming, M.D., Ph.D.
Johns Hopkins University, Maryland
Functional roles of genetic risk factors for brain disorders in neurogenesis and neurodevelopment

Copy number variations (CNVs) are deletions or duplications of genetic information on chromosomes, and they are increasingly recognized as risk factors for neurodevelopmental disorders. Understanding precisely how CNVs and other genetic variants disrupt brain development will be key to strategies to treat or prevent disease. Dr. Ming aims to advance this understanding through studies in animal models and patient-derived induced pluripotent stem cells (iPSCs).

Leonard Petrucelli, Ph.D.
Mayo Clinic Jacksonville, Florida
Expanding insights into FTD disease mechanisms

Dr. Petrucelli’s research focuses on understanding and developing treatments for frontotemporal dementia (FTD), a group of common, early-onset dementias affecting personality, behavior, and language, and for which there is no cure. The goals of his research program are to investigate mechanisms underlying FTD linked to different genetic and molecular pathways, explore therapeutic approaches, and identify biomarkers that may be used to monitor disease.  

Rosa Rademakers, Ph.D.
Mayo Clinic Jacksonville, Florida
Genetic discovery and pathobiology of frontotemporal lobar degeneration and related TDP-43 proteinopathies

Dr. Rademaker’s research has previously led to the discovery of genetic factors that cause or modify the clinical presentation of FTD. She aims to build on these accomplishments to find additional genetic causes and modifiers of FTD, and to study their functions and contributions to disease pathogenesis. This research has the potential to inform disease diagnosis, inclusion criteria for clinical studies, genetic counseling guidance, and translation to targeted treatments.

Wade G. Regehr, Ph.D.
Harvard Medical School, Massachusetts
Mechanisms and Functions of Synapses and Circuits

Dr. Regher’s research program includes basic research on synaptic plasticity, or the capacity for signaling between neurons to change, and on neuronal circuit organization and function. One line of studies will focus on the mechanisms of two specific forms of short term synaptic plasticity and their roles in different behaviors, and another will investigate circuit elements in the cerebellum important for regulating motor learning, sensorimotor integration, and social behaviors.

Jose Rizo-Rey, Ph.D.
UT Southwestern Medical Center, Texas
Mechanisms of neurotransmitter release and its regulation

The process of neurotransmitter release is fundamental to neuronal function. Although elements of the molecular machinery that contribute to this process are known, many questions remain about how they operate together to enact quick and precise release. Building on notable past accomplishments, Dr. Rizo-Rey will lead an ambitious program of studies to identify and reconstitute structural complexes involved in different stages of neurotransmitter release.  

Stephen M. Strittmatter, M.D., Ph.D.
Yale University, Connecticut
Genome-wide discovery and translational research for neural repair

A major focus of spinal cord injury research seeks to discover ways to promote the regeneration of damaged nerve fibers called axons, and thereby restore motor or sensory function. Dr. Strittmatter’s research employs advanced screening methods to identify genes that limit axon repair in the mammalian CNS. His program will conduct mechanistic studies of these genes in animal models of spinal cord injury in order to validate new therapeutic targets.

J. Paul Taylor, M.D., Ph.D.
St. Jude Children’s Research Hospital, Tennessee
Dynamic RNA-protein assemblies and neurological disease

RNA allows cells to translate genetic sequences into proteins. RNA molecules assemble with proteins inside cells to form aggregates called RNA granules, which transport, store, and regulate the translation and breakdown of RNA. Dr. Taylor’s research focuses on how RNA granules form and function, and how disturbances in these dynamics contribute to related neurodegenerative diseases such as ALS, FTD, and inclusion body myopathy.

Sally Temple, Ph.D.
Regenerative Research Foundation, New York
Defining characteristics of cortical progenitor cells over time in mouse and human

Dr. Temple has pioneered research in mice showing how the brain’s cortical architecture develops from embryonic progenitor cells through a spatially and temporally regulated process, and she is expanding her work to studies using human progenitor cells. This research will yield new knowledge about the mechanisms, timing, and regulation of human cortical development that may be leveraged to counteract developmental and neurodegenerative disorders.

Bruce D. Trapp, Ph.D.
Cleveland Clinic Lerner Research Institute (Ohio)
Pathogenesis of neurological disability in primary diseases of myelin

Myelin is a material surrounding nerve fibers that facilitates rapid signal conduction and provides essential support for neuronal growth and survival. Diseases associated with myelin damage or loss, such as multiple sclerosis, lead to nerve fiber degeneration. To inform strategies that may prevent or repair damage in myelin diseases, Dr. Trapp studies how myelin supports neuronal survival, how demyelination affects neurons and synapses, and how demyelination occurs.

Charles J. Wilson, Ph.D.
University of Texas, San Antonio
Oscillations and resonance in basal ganglia circuits

The basal ganglia are structures at the base of the brain with primary roles in motor control and learning. Dr. Wilson’s research focuses on how signal processing in locally connected basal ganglia neurons contributes to rhythmic activity generated by the overall basal ganglia circuit. These studies will refine models of basal ganglia function and dysfunction in conditions such as Parkinson’s disease, with relevance to improving treatment with deep brain stimulation.

Paul F. Worley, M.D.
Johns Hopkins University, Maryland
De novo synthesis and memory

Memory formation involves mechanisms that strengthen active synapses and weaken inactive ones, and these mechanisms depend on rapid protein synthesis inside neurons. Dr. Worley has identified key molecular effectors of this process, including the protein NPTX2. Through basic and translational studies, he will test the hypothesis that decreases in NPTX2 provide a biomarker for cognitive status in human neurological disease and may contribute to certain memory deficits.