The first six research projects funded by the One Health seed funding program were announced in late 2015 and include VCOM researchers from both the Virginia and Carolinas campuses. VCOM faculty serve as Co-PIs on these projects along with faculty members at the Virginia Maryland College of Veterinary Medicine (VMCVM). Student involvement, both from VCOM and Virginia Tech, has been high, as a goal of this initiative is to involve more VCOM students in research endeavors. Synopses of these projects are included below:
- Dr. Jennifer Berglind (VCOM Carolinas) and Dr. Irving Coy Allen (VMCVM), The Contribution of NLR Proteins in Modulating Gastrointestinal Inflammation Following Exposure to Wheat Gluten: Celiac disease is an autoimmune enteropathy that affects 2 million Americans and can result in damage to the epithelial cell layer of the small intestine. Gluten intolerance in animals has also been reported; for example, Irish Setters develop wheat-dependent partial-villous atrophy with intraepithelial lymphocyte infiltration that resembles Celiac Disease in human infants. Recent studies have shown that pattern recognition receptors (PRRs), such as TLRs, play a key role in modulating inflammation associated with Celiac Disease. The research team identified a unique sub-group of PRRs from the NLR family that significantly protect against aberrant gastrointestinal inflammation in pre-clinical animal models of inflammatory bowel disease (IBD). The overall goal of this collaboration is to elucidate the contribution of this subgroup in modulating the host immune response to gluten.
- Dr. Blaise Costa (VCOM Virginia) and Dr. Bradley Klein (VMCVM), The Role of Tri-Heteromeric (GluN1/2/3) NMDA Receptors in Stroke and its Mitigation: To protect brain from stroke induced harmful stimuli, brain cells produce a unique combination of proteins known as tri-heteromeric (TH) glutamate receptors. However, as the extent of TH receptor activity is insufficient to counter neurotoxic stimuli, eventually brain cells start to undergo death. The team aims to identify novel compounds to selectively potentiate the activity of TH receptors, which are neuroprotective. It is hoped that TH receptor selective compounds will serve as drug candidates to prevent stroke-induced neurotoxicity.
- Dr. Teresa Johnson, Dr. Renee Prater (VCOM Virginia) and Dr. Tanya LeRoith (VMCVM), Establishment of the Lamb Model of Respiratory Syncytial Virus: Respiratory syncytial virus (RSV) is a major cause of human and veterinary disease. Globally, RSV is one of the three leading causes of pneumonia in children ≤5 years of age, and is also a pathogen highly associated with bovine respiratory disease complex. The research team postulates that RSV impairs dendritic cell (DC) maturation during the initial interactions, preventing induction of sustained protective immune responses. The team will utilize the lamb model of infant RSV disease to evaluate RSV pathogenesis and the immunogenicity of candidate RSV vaccines for development of antiviral drugs and improved vaccines.
- Dr. Renee Prater, Dr. Shaadi Elswaifi (VCOM Virginia) and Dr. Nammalwar Sriranganathan and Dr. Steven Boyle (VMCVM), Nanoparticles to Deliver Antisense Nucleic Acid Constructs as Therapeutics for Intracellular Bacterial Infections: This project aims to determine whether protein nucleic acids (PNAs) can be used to control infections caused by bacteria that cause chronic infections by surviving in immune cells. The first goal of the project is to determine if PNAs can penetrate immune cells to kill bacteria surviving intracellularly. The second goal is to determine if PNAs can be used to treat animals that are infected by those bacteria. The study also aims to target bacterial antibiotic resistance genes to determine if PNAs may be used to reverse bacterial resistance to antibiotics.
- Dr. Chris Reilly (VCOM Virginia) and Dr. Xin Luo (VMCVM), HDAC6 inhibition in SLE: Systemic lupus erythematosus (SLE) is an autoimmune disease where the body's immune system becomes hyperactive and attacks healthy tissue causing inflammation and damage to many organs. Bone marrow (BM) hematopoietic stem cells (HSCs) maintain homeostasis of the immune system; HSCs rapidly proliferate and differentiate into mature lymphoid and myeloid cells which enter the blood stream. HSCs have been used to treat SLE clinically; however, in a third of SLE patients it is not effective. The research team has found that differentiation of BM B cells from HSCs is altered in diseased lupus mice. Histone deacetylase 6 (HDAC6) plays a role in transcriptional regulation, cell cycle progression and developmental events by deacetylating signaling and structural proteins. The team has found selective HDAC6 inhibition reverses aberrant BM B cell development in diseased lupus mice and decreases disease. Given the data, HDAC6 inhibition may be a novel avenue to treat or prevent SLE.
- Dr. Beverly Rzigalinski (VCOM Virginia) and Dr. Marion Ehrich (VMCVM), Cerium-Containing Nanoparticles for Amelioration of Neurodegenerative Conditions: Cerium oxide nanoparticles (CeONP) are promising agents for treatment of neurodegenerative disorders such as stroke, Parkinson’s disease and traumatic brain injury. The next step in bringing cerium oxide nanoparticles from bench to bedside demands accurate assessment of pharmacokinetic and pharmacodynamics in mammalian systems. This collaborative project addresses this critical need by examining pharmacological parameters in rats delivered cerium oxide nanoparticle by various routes of administration. Further, this study will also assess safety and toxicological findings, if any.
Additional projects awarded in the second round of funding will be starting soon.