Pilot Projects

Children's Center for Neurosciences Research has awarded eight pilot projects since its inception.  The overwhelming number of applications we have received demonstrates the growing need for neurological medical advancements and treatment options for today’s youth.  It is a privilege for our center to provide support for these studies. Through these research initiatives, we are taking strides to improve the quality of care for patients with neurological conditions.  Please see below for a description of the pilot projects funded by our center.

Robert Craig Castellino, MD, Emory University
Erwin G. Van Meir, PhD, Emory University

Thomas G. Burns, PsyD, ABPP-CN, Emory University and Children’s Healthcare of Atlanta
Tricia Z. King, PhD, Georgia State University and Georgia Institute of Technology
Richard A. Jones, PhD, Emory University and Children’s Healthcare of Atlanta
Binjian Sun, PhD, Children’s Healthcare of Atlanta
Laura Hayes, MD, Children’s Healthcare of Atlanta

Sports Related Concussion (SRC) has received a considerable amount of attention in recent years. This study will utilize neurocognitive testing in the acute (<7 days) and delayed (one month) phases of recovery to establish the severity and duration of post-concussive symptoms. Advanced neuroimaging procedures will also be utilized to evaluate cerebral blood flow, cerebrovascular reactivity, diffusion tesnsor imaging, fMRI, and morphometric analyses. This will be compared with traditional neuropsychological testing, which will include the ImPACT computerized concussion battery. These biomarkers will examined to determine (1) which factors reliably predicts the outcome of SRC, and to (2) provide insight into the mechanisms involved in SRC that will help to form prognostic judgments for determining which subjects diagnosed with SRC would benefit most from ongoing monitoring and (3) when does the physiological markers suggest the best time for to return to play when compared with neurocognitive testing.

Victor Faundez, MD, PhD, Emory University
Elizabeth R. Wright, PhD, Emory University
Nicolas S. Krawiecki, MD, Emory University

Axon growth and maintenance requires a steady supply of organelles from neuronal cell bodies. Perturbations of trafficking and organelle transport mechanisms account for a diverse group of Mendelian disorders know as axonopathies. Among these axonopathies, those generated by mutations to genes encoding WASH complex subunits in humans cause hereditary spastic paraplegia, a late-onset distal axonopathy. Our proposal will test the hypothesis that the WASH complex regulates or is regulated by components of the BLOC pathway. We will test this hypothesis using powerful mouse genetic tools and motor function assays. Our goal is to identify genetic modifiers that could alter the outcome of hereditary spastic paraplegia.

Gary J. Bassell, PhD, Emory University
Christina Gross, PhD, Emory University
Shannon Gourley, PhD, Emory University

The genetic and environmental etiologies of neurodevelopmental diseases, such as autism spectrum disorders, are highly diverse, and as a result, therapeutic strategies are lacking. The study of single-gene causes of these diseases has emerged as a promising research strategy that might further identify treatment approaches broadly applicable to larger groups of affected individuals. Recent evidence suggests that many genetic defects linked to autism converge onto a specific molecular complex within the cell – the phosphoinositide-3-kinase (PI3K)/mTOR signaling complex. For example, the most common inherited intellectual disability, fragile X syndrome (FXS), which is also frequently associated with autism, is characterized by dysfunction of the PI3K/mTOR complex. We hypothesize that reduction of PI3K/mTOR function might be a promising therapeutic strategy for FXS and other forms of autism. To test this hypothesis, we will follow a collaborative, two-pronged approach, which will characterize the effects of systemic and brain region-selective reduction of PI3K signaling on several molecular, cellular and cognitive functions in two mouse models of FXS. With this research project, we expect to generate new insight into brain region-selective functions of FMRP, and comprehensively test the suitability of PI3K reduction as a novel therapeutic strategy for FXS and possibly other developmental disabilities.

Shannon Gourley, PhD, Emory University
Kerry James Ressler, MD, PhD, Emory University

Work in the Gourley lab is driven by abundant epidemiological evidence that adolescence represents a period of increased vulnerability to the development of treatment-resistant depression. This outcome may relate to the effects of stress hormone exposure—a risk factor for depression at any age—on the prefrontal cortex, which reaches full structural maturity only at the end of adolescence. Based on this hypothesis, a major component of this proposal is to test whether genetic manipulation of two master regulators of postnatal cortical maturation, p190RhoGAP and BDNF, indeed are predictive of depressive-like behavior. Secondly, we will test the therapeutic-like properties of pharmacological agents that act on p190RhoGAP and BDNF function. There are no specialized pharmacological treatments for adolescent-onset depression; this proposal aims to better characterize the neurobiological consequences of stress hormone exposure on the structure and stability of prefrontal cortical neurons with the ultimate goal of developing specialized pharmacotherapies to treat adolescent-onset depression.

Chia-Yi (Alex) Kuan, MD, PhD, Emory University
David Archer, PhD, Emory University

Pediatric stroke is one of the most serious complications of sickle cell disease (SCD). Without treatment, 11% of SCD patients have clinically apparent stroke before the age of 20. In addition, silent cerebral infarct occurs in 27% of SCD children before their 6th, and 37% by their 14th birthdays. While chronic blood transfusion decreases the incidence of overt stroke, it triggers immune responses and iron overload, which may contribute to neurocognitive deficits of this population. Hence, the current state of preventive and acute treatment of SCD-related pediatric stroke needs further investigation and improvement. Proper use of transgenic sickle mouse models in experimental stroke may suggest new therapy, but surprisingly very little research has been conducted in this direction to this date. The GOAL of this pilot project is to establish a paradigm that is tailored for studying the cause and therapies of ischemic stroke in transgenic sickle mice. Once established, this experimental paradigm will open a multitude of research avenues.

Andrew Reisner, MD, Emory University and Children’s Healthcare of Atlanta
Jeanne Hendrickson, MD, Yale University
Silvia Bunting, MD, Emory University and Children’s Healthcare of Atlanta

Historically, coagulopathy has been recognized as an accompaniment of severe trauma. Numerous studies have shown that coagulopathy is commonly observed in patients who have sustained trauma. For decades, it was believed that the coagulopathy was a late and iatrogenic effect of transfusion of crystalloid and red blood cells, resulting in a relative or absolute deficiency of clotting factors. More recently, it was shown that the coagulopathy occurs “early”. The purpose of this study is to define the profile of coagulopathy following TBI in children, to assess the degree of platelet dysfunction and its contribution to the trauma-induced coagulopathy, and to apply association rule mining technology to evaluate the utility of thrombo-elastography (TEG) in identifying the pathophysiological mechanism involved in TBI and to direct specific coagulopathy-correcting treatments. Patients admitted to the PICU for TBI are enrolled into the study. Study labs are added that include the addition of coagulation profiles to be collected serially in the first 48 hours following admission. In addition, all patients who have sustained a severe TBI will obtain admission platelet function assays (PFA) and TEG (Regular TEG) on arrival in the ED or ICU as well as subsequent daily PFA and Regular TEG. Testing will also occur at 24, 48, and 72 hours after admission.

Andrew P. Escayg, PhD, Emory University
Sandra L. Helmers, MD, MPH, Emory University and Children’s Healthcare of Atlanta