Previous Awardees

School: School of Arts & Sciences
Department: Center for Molecular and Behavioral Neuroscience
Unit: Newark
Primary Appointment Title: Assistant Professor
Project Title: Targeting Memory Circuit Function to Develop Noninvasive Brain Stimulation Treatment Strategies for Alzheimer’s Disease
Project Description: The objective of our project is to test a novel robot guided closed-loop non-invasive brain stimulation (NIBS) intervention capable of real-time tracking and modulation of distinct episodes of memory-related brain activity (EEG) in young adults. This contribution is significant because identifying and quantifying neural circuits and proximal functions can define new targets for NIBS, tailor NIBS protocols for specific circuits and dysfunction, and more objectively measure the efficacy and outcome of NIBS for Alzheimer’s Disease. If successful, this intervention could lead to improved memory functioning in individuals with Alzheimer’s Disease.

School: School of Arts & Sciences
Department: Genetics
Unit: New Brunswick
Primary Appointment Title: Assistant Professor
Project Title: Transgenic disruption of pathogen transmission in mosquito vectors using piRNA signaling
Project Description: Mosquito-borne diseases are a leading cause of mortality worldwide, with malaria alone causing approximately half a million annual deaths. Progress from traditional methods has plateaued as mosquitoes evolve resistance to insecticides, so genetic modification of the mosquito has been proposed as an alternative to impede pathogen transmission. In the laboratory, we have created transgenic mosquitoes that are less likely to transmit the malaria parasite by capitalizing on natural processes of the insect immune system known as RNA interference. The Busch Biomedical Grant will allow us to refine and improve our technique so it can one day be deployed in field trials.

School: Ernest Mario School of Pharmacy
Department: Chemical Biology
Unit: RBHS
Primary Appointment Title: Professor and Chair
Project Title: Cell adhesion molecule L1 and metastasis
Project Description: This is a collaboration between Drs. Chen and Schachner to investigate the inhibitory activities of three antagonists of a cell adhesion molecule, L1, against metastasis in an experimental mouse melanoma model system in vivo.

School: Robert Wood Johnson Medical School
Department: Medicine
Unit: RBHS
Primary Appointment Title: Assistant Professor
Project Title: Understanding hypoxia-induced chromatin reprogramming in pancreatic cancer progression
Project Description: A deeper understanding of how pancreatic cancer progresses into metastases will enable the development of new therapeutic approaches. As one of the key contributing factors, hypoxia within the pancreatic tumor could drive cancer cells into an aggressive state that formed metastases. In this study, we identified the gene Kdm8, which encodes an oxygen-sensing histone demethylase, in the regulation of pancreatic cancer progression. Our preliminary results showed that depleting Kdm8 in pancreatic cancer cells greatly enhanced the metastasis formation in mice. Our studies aim to (1) define Kdm8 function in pancreatic cancer progression and metastasis using physiologically relevant mouse models and (2) uncover the underlying mechanisms of hypoxia-induced phenotypic reprogramming through the regulation of Kdm8 function.

School: Robert Wood Johnson Medical School
Department: Neuroscience and Cell Biology
Unit: RBHS
Primary Appointment Title: Professor
Project Title: The Role of the Microbiome and Genetic Vulnerability in Brain Development and Behavior
Project Description: Our long-term goal is to understand how both genetic (G) and environmental (E) factors contribute to neurodevelopmental disorders (NDDs), which affect ~17% of US children. Our recent children’s study indicates that antibiotics, which are commonly used in the first 2 years of life, elicit major changes in the gut microbiome and increase the risk of NDDs. In our new GxE model, we 1) define the effects of antibiotic exposure on the mouse gut microbiome, brain development, and gene expression; 2) characterize the consequences for adult NDD-related behaviors; and 3) determine whether restoring the microbiome can rescue these microbiome and neurodevelopmental abnormalities. These studies will provide insights into basic NDD mechanisms, and may inform guidelines for physician use of antibiotics during early childhood.

School: School of Arts & Sciences
Department: Cell Biology and Neuroscience
Unit: New Brunswick
Primary Appointment Title: Professor
Project Title: Inhibition of Guanine Deaminase in a Mouse Model for Human Hyperuricemia
Project Description: Gout is the most common inflammatory arthritis, with a prevalence of 4% among adults in the U.S. It is caused by elevated serum uric acid levelsor hyperuricemia. Although there are a number of urate-lowering therapies, they are contraindicated, not tolerated, ineffective, or associated with life-threatening side effects. Our proposed work establishes the principle of liver guanine deaminase as a novel target for hyperuricemia.

School: School of Nursing
Department: Nursing
Unit: Camden
Primary Appointment Title: Professor & Senior Associate Dean for Research
Project Title: Lymphatic system stimulation and fluid overload symptoms in patients with heart failure
Project Description: Emerging perspectives suggest that lymphatic system plays a critical role in fluid overload management in patients with heart failure (HF). Fluid overload is a progressive body fluid retention or redistribution that impedes multiple body system functions and leads to symptoms of pulmonary congestion (e.g., dyspnea) and systemic venous congestion (e.g., edema). Lymphatic exercises designed to stimulate lymphatic system by simulating lymphatic pumping is effective to reduce fluid level and fluid accumulation symptoms in cancer patients but it has never been tested in patients with HF, and the relationship between lymphatic system stimulation and fluid overload symptoms in HF is unknown. The overall goal of our research program is to elucidate the mechanisms of lymphatic system stimulation on fluid overload symptoms and body fluid level in HF.

School: New Jersey Medical School
Department: Anesthesiology
Unit: RBHS
Primary Appointment Title: Associate Professor
Project Title: Cellular implications of Parkinson´s disease-associated VPS35 mutation
Project Description: A point mutation in VPS35 causes late-onset autosomal-dominant Parkinson´s disease (PD) and activates leucine-rich repeat kinase 2 (LRRK2) by unknown means. Activating point mutations in LRRK2 are the most common cause of familial PD, and increased LRRK2 activity is also observed in sporadic PD cases. We aim to elucidate how mutant VPS35 activates LRRK2, and determine the effects on different cell types in the brains of mutant VPS35 knockin mice. Understanding how pathogenic VPS35 regulates LRRK2 will provide novel insights into mechanisms underlying a rare genetic cause of PD and strengthen the notion that PD patients due to the VPS35 mutation may benefit from LRRK2 kinase inhibitor treatments. In addition, identification of novel binding partners of mutant VPS35 which activate LRRK2 will warrant future work to determine their involvement in sporadic PD cases.

School: School of Arts & Sciences
Department: Chemistry
Unit: Newark
Primary Appointment Title: Assistant Profressor
Project Title: Biological transient polymer networks for environmentally responsive drug delivery
Project Description: With advent of next-generation therapeutics, such as mRNA vaccines and monoclonal antibodies, there is a pressing need to develop a next generation of versatile and responsive drug delivery systems. This project aims to establish the scientific basis for such a new drug delivery system by developing a novel biomaterial that forms a transient polymer network over which we can demonstrate exquisite chemical control. By leveraging this chemical control to tune the microscopic behavior of this biomaterial, we will further our understanding of its self-assembly and dynamic structural characteristics and progress towards the end goal of engineering it into a targeted drug delivery system that is capable of responding to changes in the local microenvironment of the body.

School: Robert Wood Johnson Medical School
Department: Biochemistry and Molecular Biology
Unit: RBHS
Primary Appointment Title: Assistant Professor (Research)
Project Title: Computational design of gene therapy viral vectors to accommodate larger genomes
Project Description: Gene therapy vectors based on Adeno-Associated Viruses (AAVs) have been successfully used in treating several genetic diseases. However, a major drawback of the AAV vectors is their inability to carry large genes due to limited packaging capacity. This precludes using these vectors to deliver large therapeutic genes such as the cystic fibrosis transmembrane conductance regulator (CFTR). There is an urgent need to increase vector capacity. AAV is a member of the large Parvovirus family. We propose to engineer a parvovirus, PPV6, that can carry much larger DNA (6.5 kb vs. 4.7 kb for AAV), as a new viral vector for gene therapy. We will expand PPV6 tropism using computational protein design and machine learning, generating libraries of viral capsids optimized for both diversity and efficacy.

School: Robert Wood Johnson Medical School
Department: Medicine
Unit: RBHS
Primary Appointment Title: Assistant Professor (Research)
Project Title: Investigating the Role of SLC45A4 in GABA Metabolism
Project Description: Solute carrier (SLC) proteins are membrane transporters that govern the cross-membrane exchanges of glucose, amino acids, inorganic ions, and other small molecule metabolites. Despite the pivotal roles of SLCs in cell metabolism and physiology, a large fraction of SLC family members are still orphan transporters without known substrates. In order to systematically study the biochemical functions of the orphan SLC transporters, we developed a computational workflow which combines public transcriptomic and metabolomic datasets to uncover the metabolic functions of SLC transporters. Using this association analysis, an uncharacterized gene, SLC45A4, was identified to be the single greatest determinant of γ-Aminobutyric acid (GABA) levels in human cancer cells. We are currently studying GABA synthesis in non-neuronal cells and the role of SLC45A4 in this process.

School: New Jersey Medical School
Department: Microbiology, Biochemistry, Molecular Genetics
Unit: RBHS
Primary Appointment Title: Associate Professor
Project Title: DNA structures that activate ATM-related protein kinase Tel1
Project Description: Protein kinase ataxia-telangiectasia mutated (ATM) plays a key role in the cellular response to DNA double-stranded breaks (DSBs). Loss of ATM function results in the pleiotropic neurodegeneration disorder ataxia-telangiectasia, characterized by the presence of progressive ataxia, frequent infections, and an increased risk of developing leukemia and lymphoma. ATM is activated at DSB sites by the Mre11-Rad50-Nbs1 (MRN) complex. Despite extensive research efforts, the detailed ATM activation mechanism is still unknown. In this proposal we will test the hypothesis that DNA secondary structure promotes ATM activation at the site of DSB using genetically tractable budding yeast as a model system.

School: Robert Wood Johnson Medical School
Department: Pharmacology
Unit: RBHS
Primary Appointment Title: Professor
Project Title: Sigma-1 Receptor (S1R) Antagonist PW507 as Opioid Adjuvant Therapy: Selective Enhancement of Opioid Analgesia with Benign Side Effects Profile
Project Description: Although opioid narcotic drugs (e.g., hydrocodone, oxycodone, morphine, fentanyl) are approved for short-term use as analgesics for acute pain (e.g., post-surgery, cancer pain), they remain controversial for long-term use (≥3 months) for chronic pain due to their myriad side effects (tolerance, addiction, etc.). The Opioid Crisis, which evolved in part from the escalation of opioid narcotic prescriptions, poses an alarming public health challenge in the US. A promising strategy for addressing this challenge is to combine the opioid with another drug (“adjuvant”) that augments the opioid’s analgesic potency to afford lower doses and reduced side effects. Employing modern drug discovery strategies, the Protect Team has discovered a novel family of Sigma-1 Receptor (S1R) antagonists that offer potential as safe and effective adjuvants to opioid analgesics. We will now test the hypothesis that combinations of our S1R antagonists and low-dose opioids may elicit the same analgesic effects as full-dose opioids but with minimal side effects.