Completed Pilot Projects
Michael Gitcho, PhD
Delaware State University
Neuronal and Glial expression of TDP-43 in Alzheimer’s Disease
The greatest risk factor for Alzheimer’s disease is aging. About 5.3 million people aged 65 and older are estimated to live with the disease. Baby boomers will add an additional 10 million cases in the next decade.
For those with Alzheimer’s disease there is an increase in plaque deposition that accelerates memory loss. The major pathological protein in frontotemporal dementia and motor neuron disease is TDP-43, which was recently found to be present in up to 50 percent of Alzheimer’s disease cases.
Dr. Gitcho’s pilot project investigates what cell types are responsible for this age-related increase in pathology. Understanding the mechanisms associated with these changes and also how age contributes could improve understanding about the progression of Alzheimer’s disease.
This mouse model potentially could lead to the development of new therapeutics targeted at slowing the progression.
Anilkumar Gopalakrishnapillai, PhD
Nemours
Metformin as adjuvant therapy to prevent relapse in pediatric acute myeloid leukemia
Acute myeloid leukemia, or AML, accounts for 15 to 20 percent of childhood leukemias. Although the majority of kids achieve remission with the existing chemotherapy treatment, half suffer a return of the disease.
Therefore, drugs that can prolong disease-free stage are needed.
Metformin is a widely used anti-diabetic drug that is known to show anti-cancerous effect in several cancer types. It is safe and non-toxic but, because of the lack of preclinical data, its inclusion in the treatment regimen of pediatric cancer, especially AML, is difficult to justify.
Dr. Gopalakrishnapillai’s pilot project aims to fill this gap by providing preclinical basis for the use of metformin to supplement existing chemotherapy. This study will also help researchers understand how metformin kills AML cells.
Shannon Lennon-Edwards, PhD
University of Delaware
Vascular Effects of Dietary Potassium in Humans
Hypertension is linked to the development of multiple kinds of cardiovascular disease in the United States. Dietary sodium restriction is an important lifestyle modification for people with hypertension, but it appears to have detrimental effects on vascular health independent of changes in blood pressure.
While sodium can increase blood pressure, potassium has been shown to be protective and to lower blood pressure in those with hypertension. Dr. Lennon-Edwards’ pilot project will use a controlled dietary study approach comparing the effects of high-sodium diets combined with either high or moderate levels of potassium on two levels of the vasculature, conduit and microvasculature. These studies will be performed in salt-resistant adults to study the vascular effects independent of changes in blood pressure.
Qi Lu, PhD
Delaware State University
Evaluating the Effects of Nanoparticles on the Packing and Organization of Lipid Domains
The goal of this study is to make clear the impact of nanoparticles on the structural organization in lipid domains in order to evaluate the potential of using these microscopic particles in preventing cancer invasion and metastasis.
Lipid rafts are floating membrane microdomains enriched in cholesterol and sphingolipids that float in the liquid-disordered phase of cellular membranes. They serve as platforms for the nanoscale assembly of membrane proteins.
The modulation of malignant phenotype of cancer cells in terms of cancer cell adhesion, aggressive invasion and metastatic spread is mediated, to a large extent, by lipid rafts.
On the other hand, silver nanoparticles, or NPs, were observed to cause the structural reorganizations of lipid vesicle bilayers and lead to an enhanced fluidization in vesicles.
Dr. Lu’s project intends to evaluate the potential of using NPs in cancer prevention and therapy in regard to the mechanism of cancer invasion and metastasis.
Michael McCulloch, MD
Nemours
Data Driven Mathematical Modeling of the Hypoplastic Left Heart Syndrome Circulation
Dr. McCulloch is a board-certified pediatric cardiologist with a passionate interest in the complex physiology and anatomy of newborns with hypoplastic left heart syndrome. The congenital condition – also known as HLHS – occurs when parts of the left side of the heart do not develop completely. It is the most common congenital heart defect resulting in death.
He proposes to produce first mathematical model of the HLHS anatomy and physiology to help answer questions about the reasons for the high mortality rate for these patients. Even with treatment, patients face a 30 percent one-year mortality rate.
This mathematical model will focus on determining the answer using bedside vital
sign data. Through three separate but interrelated methods, Dr. McCulloch and his team aim to produce a model capable of predicting impending periods of hemodynamic instability on
an individualized patient basis.
If successful, this approach could change the mortality rate for this fragile patient population by providing instantaneous, continuous feedback on a patient’s clinical status.
Thomas Planchon, PhD
Delaware State University
Adaptive Bessel Light-Sheet Flourescence Microscope (AB-LSM) for Live-Cell Imaging
Dr. Planchon’s research focuses on developing novel optical imaging technologies to enable discoveries in the field of biological sciences at large.
His INBRE pilot project aims at developing a novel optical microscope, specifically addressing a need in imaging of live cells and live biological specimens. Scientists often encounter a critical barrier while looking at specimens – the cell or organism under observation eventually dies off from light exposure, a process known as phototoxicity.
Planchon’s research proposes to create a microscope that can film live specimens without killing them. The tool, called the Adaptive Bessel Light-Sheet microscope, gets its low toxicity by using a computer-controlled liquid crystal device to generate the thinnest light-sheet possible – 100 times thinner than the width of an average human hair.
This imaging technique method could be used in cancer, cardiovascular or neuroscience – the three research areas under Delaware INBRE.
David Pokrajac, PhD
Delaware State University
Improving Realism of Software Breast Phantoms
Breast cancer is the most common cancer among American women, except for skin cancers, and the second leading cause of cancer death. Continuous improvement and innovation of affordable medical imaging systems that can provide high-sensitivity and high specificity breast cancer screening is essential to decrease the burden of cancer on public health.
Dr. Pokrajac’s project addresses the need to speed up the translation of breast imaging research to clinical reality by improving the quality of preclinical validation of novel imaging systems.
Motivated by the need to increase the realism of software breast phantoms – which offer flexibility to simulate anatomic variations and provide ground truth for simulated tissue structures – he proposes to develop novel simulation algorithms, obtain the optimal values of phantom parameters and validate the approach using simulated and clinical images.
He will determine optimal values of phantom parameters using histologic imaging and segmentation of reconstructed mastectomy computed tomography data. The simulated images
will be validated by comparison to the clinical images through objective and subjective validation.
The ultimate goal of the proposed modification is to set the foundation for a larger-scale NIH funded projects on the extension of breast imaging simulation to digital breast pathology
Rhonda Prisby, PhD
University of Delaware
Characterization of Bone Marrow Microvascular Ossification in Rodent and Human Long Bones
Vascular origins of bone diseases like osteoporosis are poorly understood and understudied.
Dr. Prisby has discovered severe calcification of bone marrow blood vessels in a rodent model of aging. Her pilot project seeks to address the consequence associated with bone marrow blood vessel ossification by characterizing the development and progression of the pathology as a function of age.
If such pathology is evident in the human skeletal system, results would perhaps provide some explanation for the development of bone disease and the complications associated with poor fracture healing with advanced age.
Successful completion of this project could provide paradigm-shifting causes of bone disease, which are vascular in nature, and aid in understanding the development, progression and the inefficacies of pharmaceutical treatment in bone disease.
Regina Sims Wright, PhD
University of Delaware
Diet Quality, Inflammation, and Cognition: An Analysis of the HANDLS Study
Poor diet quality is a significant predictor of cardiovascular disease, the top cause of death in the U.S. It also has been linked to cognitive difficulties, and growing evidence suggests inflammation is the primary pathway of influence.
No studies have examined how individual components of diet quality influence these complex associations. Moreover, none have examined this association in a racially diverse sample, which is problematic because poor diet quality is more common among African Americans as compared to whites, in part because of socioeconomic and cultural barriers.
Dr. Sims Wright plans to use data from the Healthy Aging in Neighborhoods of Diversity across the Life Span study, or HANDLS, to disentangle the mechanisms linking diet quality to cognitive function through inflammatory pathways.
Her research aims to make a meaningful contribution toward understanding the roles of numerous components of the diet to inflammatory and cardiovascular pathways that may contribute to cognitive decrements and how these pathways may vary as a function of race.
Jennifer Sims-Mourtada, PhD
Christiana Care Health System
Molecular Mechanisms to Distinguish Aggressive Tumors
A large proportion of prostate tumors occur as indolent tumors that are clinically insignificant. But a minority these are fast growing, malignant cancers that need significant clinical intervention.
Currently, the molecular mechanisms to distinguish indolent from aggressive tumors is unknown.
Dr. Sims-Mourtada’s project proposes that these aggressive tumors “prepare the soil” of the metastatic microenvironment by increasing the sensitivity of bone marrow stromal cells to factors secreted by tumor cells.
Her project examines the role of stromal primary cilia – which are non-moving structures that serve as beacons for cellular signaling – on growth and survival of prostate cancer cells. She hopes to determine if localization of hedgehog signaling components – a factor that binds to receptors on the cilia – promotes survival of prostate cancer cells.
John H. Slater, PhD
University of Delaware
Modular Arrays of Vascularized Multi-Cellular Micro-Tissue Constructs for High-Throughput Drug Screening
The delivery of new marketplace therapeutics for the treatment of cardiovascular disease and cancer is hampered by two challenges: the high cost of new drug development and a high failure rate. The average expenditure to introduce a new drug is $802 million, with some reaching $5.5 billion.
But the level of risk for a company to generate a new therapeutic could be lowered through the use of more physiologically relevant in vitro screening models and lead to an increased selection of disease‐specific therapeutics with increased efficacy.
Three‐dimensional cell culture systems that more closely replicate the physiological conditions encountered by cells in vivo are being developed. These systems are anticipated to serve as better preliminary screening models with the potential to replace animal models in the future.
Dr. Slater’s work in his pilot project outlines a methodology to address one of the major limitations with current three-dimensional cell culture platforms: the ability to create highly vascularized fluidic systems embedded in synthetic matrices for nutrient delivery and waste removal.
Megan W. Wenner, PhD
University of Delaware
Reproductive Aging and Vascular Function
Cardiovascular disease is the leading cause of death in women. Young women are generally thought to be protected because of the vaso-protective effects of estrogen.
But there is a decline in estrogen as women transition to menopause. Postmenopausal women have impaired vascular function that can be reversed by estradiol therapy. Recently, there has been controversy regarding the safety and efficacy of hormone therapy in menopausal and postmenopausal women, specifically questioning whether estradiol therapy offers cardio-protection to these women.
The ‘timing hypothesis’ suggests that starting hormone therapy early in the menopausal transition – before atherosclerotic disease is present – can offer cardio-protection and help alleviate menopausal symptoms such as hot flashes.
Dr. Wenner’s project is investigating the effects of reproductive age and estradiol on ET-1 mediated microvascular vasoconstrictor function in peri-menopausal women. ET-1, or endothelin-1, is a potent vasoconstrictor that has been implicated in the development of atherosclerosis. Functional changes in the microcirculation can be used as an index of future cardiovascular disease risk.
