CVM awards $1.2 million to wide range of Intramural Projects

Twelve research projects were recently awarded funding through the CVM intramural Internal Grants Program. The intramural program is designed to foster research in any of the CVM’s nine areas of research, which capture the range of work at the college impacting the health of animals, humans, and the environment. Formerly known as the signature program, the intramural program made a total of $1.2 million in funding available to CVM researchers in 2023. 

This year’s funding was distributed to 12 individual projects through a competitive application process only open to CVM researchers. Read about the 2023 funded projects below. Congratulations to the awardees!

Erin Dickerson (VCS), “Targeting molecular subtypes of canine hemangiosarcoma”

Hemangiosarcoma (HSA) is a highly aggressive cancer that commonly affects dogs and leads to a significant number of deaths each year. Unfortunately, there is currently no definitive cure for this disease, making effective treatments crucial in veterinary medicine. In human medicine, the drug propranolol has shown promise in improving survival for people with a similar cancer called angiosarcoma. Previous studies by our group suggest propranolol may be an effective treatment for a subset of dogs with HSA. In this project, we aim to investigate Yes-associated protein 1 (YAP1) as a novel target of propranolol and to identify its role as a driver of this newly identified subtype of HSA. By better understanding the interactions between propranolol and YAP1, we hope to pave the way for more effective and targeted therapies to treat this aggressive disease. 

Sagar Goyal (VPM), “mRNA vaccine against porcine reproductive and respiratory syndrome virus”

Porcine reproductive and respiratory syndrome virus (PRRSV) causes huge economic losses to the swine industry despite the availability of vaccines. This is primarily due to continuous variation in PRRSV strains. An mRNA vaccine will reduce these problems because it will be easier and quicker to substitute the newly emerging strains of PRRSV in mRNA vaccine. Therefore, this project’s objective is to develop mRNA vaccines against PRRSV and evaluate them in vivo in pigs for safety and efficacy.

Alonso Guedes (VCS), “Defining the role of CD38 signaling in depolarization-secretion coupling of pre-synaptic sensory neurons”

Limitations of presently available analgesics contribute to the unsolved problem of chronic pain in animals and humans. The research team is working to discover and characterize a previously unknown pain modulatory system in the spinal cord centered on CD38, an enzyme involved in intracellular calcium regulation. The main goal of the project is to define the role of CD38 signaling in the pre-synaptic component of spinal sensory transmission. This understanding is critical towards the development of novel therapies for chronic pain. 

Yinduo Ji (VBS), “Role of putative cobalt transporter in MRSA biofilm formation”

Methicillin-resistant Staphylococcus aureus (MRSA), including livestock-associated MRSA, is a serious public health concern worldwide due to the limited therapeutic options to treat MRSA infections. MRSA infections are even further complicated by the ability of S. aureus to form biofilms, especially on indwelling medical devices. It is extremely difficult to eradicate biofilms due to the increased tolerance of bacterial cells to antimicrobials in biofilms. Therefore, there is an urgent need to develop a novel strategy to combat multidrug-resistant MRSA. Our pilot studies indicate that a putative cobalt transporter ATP-binding subunit CbiO is required for MRSA biofilm formation. Interestingly, we revealed that supplementation of a chemically defined medium with extra Cu²⁺ but not Co²⁺ ions can restore biofilm formation for the CbiO null mutant. The objective of this proposal is to determine the role of the putative cobalt transporter in S. aureus biofilm formation in vitro and in vivo and pinpoint the mechanism of copper ions mediated biofilm formation. 

Casey Johnson (VCS), “Quantitative MRI of canine patients with intervertebral disc disease”

The objective of this project is to investigate the health of the intervertebral discs, vertebral bodies,and spinal cord in canine patients with intervertebral disc degeneration (IVDD) using quantitative MRI. Intervertebral disc degeneration is a spine disorder in dogs that can result in chronic pain, paralysis, incontinence, and even death. IVDD is caused by diminished structure and function of the intervertebral discs, which can then herniate and compress the spinal cord and nerves. Current clinical imaging has limited ability to assess disc health and resultant spinal cord injury, which inhibits identification of problematic and painful discs and hampers treatment decisions and options. By better understanding the relationships between the health of the intervertebral discs, vertebral bodies, and spinal cord, we will be able to help advance clinical management of IVDD.

Kevin Lang (VBS), “Impact of host-pathogen interactions on genomic integrity and oncogenesis”

The objective of this study is to determine the molecular mechanism driving host DNA damage during Listeria monocytogenes (Lm) infections. Several bacterial infections have been linked to increased risk of cancer in humans. The foodborne pathogen Lm has been shown to induce host DNA damage. However, the mechanism behind this is unknown. This project’s work will enable the determination of the molecular mechanisms responsible for bacterial-induced DNA damage. Understanding the cellular pathways that respond to bacterial infections may lead to novel potential therapeutic options, and establish foodborne infections as potential cancer risk factors.

Peter Larsen (VBS), “Characterizing the effects of anthropogenic land use change on mosquitoes and arboviruses in an Amazonian indigenous reserve”

Mosquito-borne arboviruses are a significant threat to global health. The Amazon rainforest contains the greatest number of mosquitoes and arboviruses on the planet. Due to extensive deforestation, Amazonia now consists of either highly fragmented forests or large, mostly undisturbed Indigenous reserves. Our current knowledge of sylvatic mosquitoes comes from fragmented forests. This project’s objective is to characterize how anthropogenic land-use change of intact rainforests influence the distribution and diversity of mosquitoes/arboviruses. The team will collect mosquitoes across a disturbance gradient, morphologically identify mosquitoes and screen for arboviruses using advanced nanopore sequencing approaches. An overarching goal is to create Indigenous-led community-based monitoring of mosquito vectors and mosquito-borne pathogens in Amazonia. 

Hinh Ly (VBS), “Comparative animal model of human pregnancy-associated complications due to Lassa virus infection”

This project’s objective is to evaluate whether Pichinde virus (PICV) infection in guinea pigs could be used as a comparative animal model of Lassa virus (LASV) infection of pregnant women and to identify mechanisms that cause adverse pregnancy outcomes post-infection. Pregnant women are uniquely vulnerable to certain types of viral infection and there is an unmet need to identify vaccines and therapeutics to protect them from high risk pathogens, such as LASV. 

Timothy O'Brien (VPM), “Development of an organoid-derived exosome product for the treatment of osteoarthritis”

This project will leverage multi-tissue organoid (MTO)-derived cartilage as a source of exosomes to develop an off-the-shelf, disease-modifying therapy for osteoarthritis (OA). OA is a chronic debilitating joint disease, afflicting over 32 million people in the US. It affects over 40% of those over 55 years old, with women more commonly affected, and incidence increases with age, joint overuse, and obesity. As the population ages, those rates are expected to double by 2040. There is no approved therapy to slow or reverse the progression of OA. Existing treatments are focused on symptom relief and do not arrest the progression of the disease. The team has shown in vitro that their exosome product has anti-inflammatory activities and induces chondrocyte proliferation, and may thereby slow OA progression or reverse the tissue damage in OA.  In this study they will assess the MTO-derived exosomes by analyzing their contents and further investigating their immune modulating activities, and by testing them as a therapeutic in a rat model of knee OA.

Roberta O'Connor (VBS), “Identification of the target of euryponolide, a potent new anti-Cryptosporidium compound”

The objective of this project is to identify the molecular target of euryponolide, a new marine natural product with potent anti-Cryptosporidium activity. There is no effective treatment for cryptosporidiosis, a zoonotic, waterborne, parasitic infection that causes significant illness and death in both developing and industrialized countries. Immunocompromised patients of all ages are highly susceptible to Cryptosporidium infection. Also causing significant challenges for animal agriculture, the parasite is now recognized as endemic in cattle operations worldwide. There are no therapeutics to treat cryptosporidiosis in neonatal ruminants. Therefore, development of effective therapies for cryptosporidiosis is both a medical and veterinary imperative and a critical One Health issue. 

Bruce Walcheck (VBS), “Targeted ADAM17 blocker to enhance human and canine natural killer cell proliferation for treating cancer”

Natural killer (NK) cells are lymphocytes of the innate immune system that can directly kill tumor cells and have become a major focus of cancer immunotherapy. Points of interest include their use as an adoptive cell therapy (ACT), derived from the patient or a donor, delivered to cancer patients—humans and dogs—for various malignancies. The objectives of this project are to generate engineered antibodies that contain interleukin-15 and simultaneously bind to NK cells and tumors in humans or dogs using established molecular and cell expression techniques. These multi-specific antibodies will be investigated for enhancing NK cell killing of tumor cells.

Zheng Xing (VBS), “Development of mucosal immunity-based universal DNA vaccines for H5Nx avian influenza in turkeys”

Avian influenza virus (AIV) has always posed a significant threat to poultry. Developing more effective vaccines for AIV in turkeys is critical for stopping the trend of increased AIV, especially HPAI, outbreaks in poultry. There are currently no vaccines available for H5Nx HPAI in turkeys. Traditional inactivated vaccines for a systemic immune response do not provide effective protection against AIV in turkeys. The objective of this project is to develop universal H5Nx DNA vaccines that are delivered by non-pathogenic Salmonella and probiotic Lactobacillus strains in turkey breeders to induce mucosal immunity in the GI. We will determine the vaccine’s immunogenicity for the induction of both systemic and mucosal antibodies with different carriers and compare their protective efficacies against an H5N2 AIV in challenged turkey breeders.