Pilot Projects

The Delaware INBRE Pilot Awards offer needed assistance to early-career investigators on the path to research independence.

 

Pilot Projects 2021-2023

 

Mitra Assadi-Khansari, MD
Pediatric Neurology
Christiana Care

Project title: Enhancement of behavioral and cognitive outcomes in autism via neurostimulation

Thematic area: Neuroscience

Summary: Autism spectrum disorder (ASD) encompasses a wide range of limitations in reciprocal social and communicative milestones, as well as restrictive and/or repetitive patterns of behavior which lead to significant functional challenges impacting individuals throughout their lifespan. The clinical, social and financial burdens of ASD are staggering, and yet, despite the gradual increase in the incidence, the therapeutic alternatives remain extremely limited and ineffective. Moreover, there are no interventions to improve social cognition. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neurostimulation technique which alters the cortical excitability by repeated induction of electromagnetic activity. Receiving FDA approval in 2013 for depression, rTMS is a promising tool in the field of neuropsychiatry. The overarching aim of this project is to demonstrate the efficacy rTMS in improving social and cognitive outcomes in ASD by stimulating the mirror neurons populated in the inferior parietal lobule (IPL).

 

Carissa Baker-Smith, MD, MPH
Dir. of Preventive Cardiology, Division of Cardiology, Department of Cardiovascular Medicine
Nemours

Project title: Neighborhood Deprivation Index Predicts Loss of Ideal CV Health in Adolescents

Thematic area: Cardiovascular

Summary: The American Heart Association’s (AHA) “Life’s Simple 7 Metrics” defines ideal cardiovascular health (ICVH) as the presence of 4 health behaviors (healthy diet, regular physical activity, normal body mass index (BMI), never smoked/vaped) and 3 health factors (normal total cholesterol (TC-c), blood pressure (BP) and blood glucose (BG)). In adulthood, ICVH is associated with lower rates of premature cardiovascular disease (CVD). When present at 18 years of age, ICVH is associated with a nearly 70% lower risk of premature CVD. However, most adults do not possess ICVH5 and it is now recognized that CVD begins in youth. Deprivation index (DI), a measure of neighborhood (e.g., NDI) or area deprivation (e.g., ADI) is associated with the loss of ICVH; it is unknown when in life DI impacts CVH status. DI is defined as the low physical, social and economic position of a community. DI plays a key role in the absence of ICVH in adults, but the impact of DI on CVH status in children has not been studied. This project will help to determine if DI is associated with loss of ICVH status during adolescence.


Amanda Hernan, PHD
Research Scientist, Head of the Dynamics in Epilepsy and Cognitive Development Lab at Nemours, Assistant Professor of Psychological and Brain Sciences University of Delaware
Nemours

Website

Project title: A role for astrocytes in treatment of cognitive deficits after early life seizure

Thematic area: Neuroscience

Summary: Astrocytes are crucial for the normal development of neurons, are actively involved in neuronal signaling and are crucial for maintaining excitatory/inhibitory balance, and are damaged in adult epilepsy. We have previously shown that ACTH has actions beyond its systemic effects alone in this animal model and may be acting through a subtype of neuropeptide receptors in the brain to improve outcome after recurrent early life seizures (ELS); indeed, very recent preliminary data indicate that ACTH is only effective in animals that express melanocortin 4 receptors (MC4Rs) in the brain. These receptors are on neurons but also astrocytes, one of the most abundant cells in the brain. This project is designed to understand the role of astrocytes and MC4Rs on those astrocytes in altering the way neurons communicate after ELS.

 

Hakeem Lawal, PHD
Associate Professor Biology
Delaware State University

Website

Project title: Characterizing the Neuroprotective Properties of a Putative Anti-Parkinson’s

Thematic area: Neuroscience

Summary: The overall goal of this project is to delineate the neuroprotective properties of dacarbazine, a compound that we identified in a previous screen for putative anti-Parkinson disease therapeutics. There is no known cure for Parkinson’s disease (PD) and current drug treatment options are of limited efficacy or induce serious side effects. The work proposed could help advance strategies for the development of effective treatment for PD and possibly point to disease modifying therapies against that disorder.

 

Fabrizio Sergi, PHD
Assistant Professor Biomedical Engineering
University of Delaware

Website

Project title: Simultaneous TMS and fMRI to study causality of neuromuscular pathways

Thematic area: Neuroscience

Summary:  This project aims to establish causality in the function of the corticospinal and reticulospinal pathways, which serve a fundamental role in post-stroke recovery. This project aims to develop and validate a new methodology, which combines transcranial magnetic stimulation (TMS) with functional magnetic resonance imaging (fMRI) of the brainstem, to study the response of brainstem nuclei during motor responses essential for the control of human movements, the long-latency responses. Our work is enabled by a new MRI-compatible TMS amplifier available at our imaging center, and by our own previous work on the integration of robotics with fMRI to quantify function of the brainstem associated with long-latency responses. If successful, this project will yield the first demonstration of successful combination of TMS and fMRI to study causality of neural function in a distributed motor circuit, involving the primary motor cortex and the brainstem, involved in control of motor tasks. This project will open a new and unique window of observation in the neural substrates of motor impairment and recovery after stroke. Understanding the fundamental neurophysiology of primary and secondary pathways is a necessary step required before applying similar investigations to post-stroke individual.

 

Kevin Solomon, PHD
Assistant Professor of Chemical & Biomolecular Engineering
University of Delaware

Website

Project title: Barley Stripe Mosaic Virus as an RNA Vaccine Vector for Cancer Immunotherapy

Thematic area: Cancer

Summary: RNA vaccines have recently emerged as promising cancer immunotherapies for otherwise untreatable cancers. These therapies aim to stimulate macrophages of the immune system to fight tumors marked with antigens encoded in their RNA cargo. The effectiveness of these approaches is substantially improved by vaccine carrier design; carriers must effectively deliver their cargo to antigen-presenting cells and stimulate activation of immune pathways, but not otherwise confer toxicity or deleterious immune responses. Conventional carriers, unfortunately, are limited in their ability to present ligands that stimulate an immune response, may be toxic, or otherwise interact with the immune system in undesirable ways. This project evaluates a novel vaccine carrier based on the plant barley stripe mosaic virus (BSMV) for the delivery of RNA vaccines. The plant-based origins of BSMV promises a lower risk of deleterious immune responses while its well-established design rules allow for unparalleled engineering opportunities to enhance immune activation. More importantly, the RNA promiscuity of BSMV and similar studies with other plant virus suggest a high capacity for the delivery of RNA payloads.

 

Shubhika Srivastava, MD
Pediatric cardiologist, Chief of the Cardiology Department
Nemours

Project title: Development of a risk stratification tool to identify role of cardiovascular involvement in children and young adults following SARS-COV2 infection and or exposure

Thematic area: Cardiovascular

Summary: Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV2) is spreading all over the world and poses a great threat to humans. Its impact on children and young adults has been evolving. Reports of cardiovascular involvement range from asymptomatic to those severely impacted directly by the virus or suffer consequences of a multi systemic inflammatory response that can affect the heart (MIS-C) and other organ systems. Early and long-term sequelae continue to be defined. Existing comorbidities, race and ethnicity and age impact the prevalence of cardiac involvement. There is paucity of data regarding cardiovascular involvement in COVID -19 in children. This makes management decisions difficult especially when clearing children and young adults for sports participation. Approximately 35 to 45 million youth 6 to 18 years of age participate in some form of athletics. With reopening of schools and variable infection rates, the actual burden of COVID -19 infection and its impact on this population (10 years- 30 years age) is unclear as is utilization of cardiovascular testing. Our objective is to build a risk stratification tool specific for patients positive for COVID19 based on a large data enclave representative of the population who tested positive for COVID -19; the National COVID database (N3C).

 

Murali Temburni, PHD
Associate Professor
Delaware State University

Project title: Role of astrocytic GPCR pathways in the development of synchronous activity of neurons in culture

Thematic area: Neuroscience

Summary: The central hypothesis of this project is that during development signaling between astrocytes and neurons is crucial for the establishment of synchronously oscillating neuronal networks. Our preliminary results using the developing chick embryonic brain as a model system indicate that astrocytes are necessary for synchronous activity of neurons in culture. We have developed a model in which astrocytic G Protein Coupled Receptors (GPCR) sense neurotransmitter, elevate intracellular Ca++ flux and in turn release “gliotransmitters” like glutamate and ATP. We implicate the metabotropic glutamate receptor (mGluR), the purinergic P2Y1 GPCR and the metabotropic GABA-B receptor in the development of neuronal synchrony. For this project, we will test the astrocytic GPCR model bidirectionally – by activating the pathway with optogenetics using melanopsin, a light activated photopigment and blocking the other two GPCR pathways (P2Y1 and GABA-B) with dominant negative proteins).

 

Elizabeth Wright-Jin, MD
Pediatric Neurologist
Nemours

Project title: Sex and microglia in neonatal hypoxic ischemic brain injury

Thematic area: Neuroscience

Summary: Hypoxic ischemic injury is a leading cause of cerebral palsy in infants born at term gestation. Children who sustain these injuries early in life can be left with debilitating cognitive and motor deficits. Therapeutic hypothermia has reduced the incidence and severity of these injuries, however, many children develop cerebral palsy and intellectual disability despite this treatment or do not receive this treatment within the short time window it must be initiated after birth. Notably, boys have a higher likelihood of developing cerebral palsy than girls. Animal studies have begun to reveal sex-specific responses to neonatal brain injury may underlie this increased risk in males. Microglia, the primary immune cell in the brain, have a major role in sexually dimorphic brain development; and given their central role in response to brain injury, microglia may influence this discordant outcome. This project will investigate the influence of sex on microglia response after neonatal hypoxic ischemic injury.