2024 Innovation & Discovery Grants
The Foundation for The Horse set a record in 2024 by awarding $664,467 for 18 research projects at 12 institutions. These grants include 11 Innovation and Discovery Research Grants to established equine researchers investigating novel approaches to an array of conditions affecting equine health and welfare. (See also Young Investigator Research Grants.)
Now in its third year, the Innovation and Discovery Research Grants program, supported in part by a generous gift from Mrs. Penelope Knight and Coyote Rock Ranch, has awarded more than $978,000 to support 18 projects by 17 veteran equine investigators.
The Innovation and Discovery Research Grant program’s capacity to award funds increased significantly due to Mrs. Knight’s gift in the fall of 2023 and The Foundation’s increased investment of $3 million in overall support for its mission impact for the 2024-2025 funding cycle. That amount honors The Foundation’s 30th anniversary.
For the fifth consecutive year, the Thoroughbred Education and Research Foundation (TERF) partnered with The Foundation to help make these research projects possible. TERF, whose mission is to make racing safer through research, education, and scholarships, provided funding and collaborative support for one Innovation and Discovery grant. Since 2020, TERF has partnered with The Foundation on nine projects totaling $153,404.
Following is the list of 2024 Innovation and Discovery Research Grants:
RESEARCH PROJECT: Targeting lipopolysaccharide composition of Salmonella enterica serovars to increase susceptibility to equine macrophage host defenses
Salmonella enterica is a serious threat to equine health worldwide and is the leading cause of intestinal disease often associated with laminitis. The existence of many Salmonella enterica serovars that infect horses with differential resistance to antibiotics, causes additional therapeutic complications. Therefore, identifying new targets for drug therapies is needed. Macrophages are essential for immunity against bacterial infections by producing and concentrating antimicrobial molecules in phagosomes to kill microbes. Our previous work has identified a critical role for lipopolysaccharide (LPS) modulation in evading macrophage killing. However, mechanisms by which various Salmonella enterica serovars evade equine macrophage killing to cause intestinal disease is unknown. In this proposal we aim to characterize how different Salmonella enterica serovars modulate their LPS structure to evade equine macrophage host defense, and identify drugs that target the LPS biosynthetic pathway to increase Salmonella enterica susceptibility to host antimicrobials including macrophage killing. The proposed study will reveal a new class of antibiotics that can be leveraged for development of treatments for infection by multi-serovar pathogens.
RESEARCHER: Dr. Basel Abuaita, Louisiana State University
RESEARCH PROJECT: Development of sdAb to block endotoxin in horses (second year of grant)
Horses are very susceptible to the deleterious effects of endotoxin. This is seen most commonly with GI ailments such as colic or salmonellosis, or also with neonatal sepsis. We are attempting to develop novel antibody fragments that can be used as a treatment to lessen the effects of endotoxin in horses. These antibodies should bind active sites on endotoxin, and prevent to over-activation of immune cells. We already developed candidate antibodies in the first part of this study. Now, we wish to test their efficacy in preventing the activation of equine white blood cells.
RESEARCHER: Dr. Christopher Cebra, Oregon State University
RESEARCH PROJECT: Characterization of Sarcocystis neurona rhoptry proteins translocating into the host cell (two-year grant)
In the United States, more than 75% of horses get exposed to Sarcocystis neurona and risk developing a neurological disease called equine protozoal myeloencephalitis (EPM). Sarcocystis neurona cannot live outside the host cells. In an infected horse, S. neurona lives in the brain and spinal cord. Damage caused by parasite replication results in varying degrees of lameness, muscle atrophy, difficulty swallowing and breathing, or even death. Affected horses undergo prolonged treatment with expensive drugs. However, in some cases, neurological disease reappears when therapy is discontinued. This could be possible because the intracellular parasite may be hiding or has hijacked the host cell. Our goal is to understand the interaction between the host and S. neurona so that a disruption of this interaction can reveal the parasite to the host. The drugs and immune cells can then get to it. In silico analysis of two rhoptry kinase proteins from S. neurona indicates that they interact with the host cell. We propose to perform wet-bench experiments to determine if the computer predictions are accurate. Our experiments include (i) tagging these parasite proteins to make them glow and following them by microscopy to find out where they end up in the host cell. (ii) Use the tagged proteins as bait and identify who they interact with inside the host cell. (iii) If we destroy these proteins, how will they impact the parasite’s growth? The outcome of these experiments will tell us how these proteins are helpful for the parasite and if breaking this interaction will benefit the host cell.
RESEARCHER: Dr. Sriveny Dangoudoubiyam, Purdue University
RESEARCH PROJECT: Nanoparticle Immunotherapy for Treatment of Squamous Cell Carcinoma in Horses
This study will investigate the safety and efficacy of a new type of immunotherapy, which potently activates host immune responses against tumor cells, in horses with aggressive genital cancer due to squamous cell carcinoma. This immunotherapeutic, which consists of small immune stimulatory particles and is administered by direct tumor injection, has already demonstrated efficacy in horses with corneal and eyelid squamous cell carcinoma and in four horses with genital cancer. This new immunotherapy therefore holds promise as a new injectable immunotherapy for cutaneous cancers of horses generally.
RESEARCHER: Dr. Steven Dow, Colorado State University
RESEARCH PROJECT: Air-borne transmission of Equid alphaherpesvirus 1 (EHV-1)
EHV-1 is a cause for respiratory and neurologic disease in horses. This virus spreads through infectious secretions produced in the respiratory tract into others, either via direct contact between 2 horses; via touching hands, gear or equipment (fomites), but also via air-space via droplets and aerosols. For reasons of biosecurity at home barns or at equestrian events, we need to define a safe distance between two horses that prevents transmission. A study in calves suggests a distance of approx. 15 feet (4.4 meters); however, this distance has not been tested for the prevention of EHV-1 infection in horses. From a clinical stand-point we don’t believe that this distance is sufficient to prevent infection. We believe that multiple days of shedding by an infected will allow some (moderate) stimulation of an immune response in the exposed horses. We want to characterize the immune response in the exposed horses, and we want to test the resilience of this immune response. After this experiment we will know about efficacy and value of a 15 ft distance between a shedding and exposed horses. We can make science -based recommendations to the equine industry.
RESEARCHER: Dr. Lutz Goehring, University of Kentucky
RESEARCH PROJECT: Quantifying functional back movement in the reining Quarter horse
The back plays important roles during movement of the horse. Its role changes for example in relation to gait, or the surface a horse is exercised on or whether the horse moves straight or in circles. Little is known in practical terms about how the horse ‘tunes’ its back in order to efficiently perform different tasks.
Our study sets out to quantify back movement – with small wireless inertial measurement units – and back muscle activity – with wireless electromyography – in Quarter horses exercising in different gaits, on different surfaces and during straight-line and circular exercise. We are choosing reining Quarter horses as an example breed that is regularly exposed to a variety of athletic tasks and as a specific group for which we have recently collected back movement and movement symmetry data. Studying different exercise conditions will allow us to improve our understanding about how horses activate back muscles allowing them to efficiently perform under a variety of conditions. Drawing from an existing data base of back movement (but not muscle activity) data of our research group collected from varying breeds and disciplines under similar exercise conditions, we aim to maximize the generalizability of our findings by assessing similarities (and differences) with movement characteristics of our cohort of Quarter horses. The results of our study will be the first comprehensive data base of functionally relevant back movement and muscle activation characteristics for a specific group of athletic horses.
RESEARCHER: Dr. Thilo Pfau, University of Calgary
RESEARCH PROJECT: Proteomics and A2M Reagents for Arthritis (second year of grant)
Our laboratory seeks to improve the ability of equine practitioners to diagnose and treat osteoarthritis (OA) in horses. OA is the primary cause of lameness in horses of all ages, breeds, and disciplines. While the area of therapeutics for managing joint disease in horses continues to expand it can easily outpace the current body of knowledge, and this proposal seeks to fill some of this gap. First, we propose expanding our ability to measure alpha-2 macroglobulin (A2M) through creation of an equinespecific antibody. A2M is an anti-inflammatory protein currently available for treating OA in humans and
horses, and in several species in increased in OA-affected joints. This protein can be measured in humans, however there are no reagents available to measure A2M in horses. By developing an antibody that recognizes equine A2M we will expand our ability to quantitate this protein. Additionally, we seek to expand our previous work evaluating proteins present within joint fluid from horses with knee (carpal) OA to the joint fluid and blood from horses with ankle (fetlock) OA. This expansion will confirm the validity of potential diagnostic and therapeutic protein markers across multiple joints and determine whether any systemic blood markers of OA exist in the horse.
RESEARCHER: Dr. Heidi Reesink, Cornell University
RESEARCH PROJECT: Prevalence of insulin dysregulation and laminitis (second year of grant)
Laminitis or Founder remains a major cause of suffering and death in horses, yet our understanding of prevention and treatment of this devastating process remains poor. Recent research from the United Kingdom and Australia has established a clear link between insulin dysregulation (ID) and lifetime laminitis risk. To date, there has only been one ID epidemiologic study from the United States, which identified high baseline plasma insulin levels in 18% of horses, most of which were obese. No studies to date have evaluated the prevalence of ID utilizing the oral sugar test (OST)to improve diagnostic sensitivity, so the true prevalence of ID may be higher than previously reported. Additionally, no studies to date have examined the relationship between ID and the prevalence of subclinical laminitis, meaning radiographic signs of laminitis without clinical lameness. This study aims to test a large population of sport horses in the United States for ID using the OST and for subclinical laminitis using foot radiographs. We hypothesize that the prevalence of ID will be higher than previously reported, particularly in non-obese horses, and that a subset of horses with ID will have radiographic changes consistent with previous laminitis. This information will be utilized to provide equine veterinarians with guidelines on the stall-side screening of patients for these risk factors, especially prior to corticosteroid administration. Diagnosis of ID and subclinical laminitis is critical for early intervention to reduce the risk of future clinical laminitis episodes.
RESEARCHER: Dr. Lauren Schnabel, North Carolina State University
RESEARCH PROJECT: Sodium and glucose transport in equine diarrhea
The horse has a unique intestinal tract among animals. Because of this, studies on the intestine performed in other species, such as mice, are often not applicable. One of the ways in which diarrhea occurs is through “turning on” and “turning off” the ion channels found on the gut’s lining. Normally the channels help the horse absorb and regulate nutrients and ions. If the channels are not working properly and are either actively secreting or not absorbing substances such as sodium, glucose and chloride, diarrhea results as water follows these substances. The first goal of our project is to make sure that rectal tissue mimics the large intestine well enough to serve as a model. Previously, in order to study the horse’s intestine, samples had to be obtained through invasive methods, including surgery or after death. We are modeling the horse’s intestine using cells grown from a rectal biopsy. The horse only needs to be lightly sedated to obtain this sample. The second goal is to determine how the harmful bacteria commonly known as C. diff (Clostridioides difficile) causes diarrhea in the horse. C. diff produces a toxin that may turn off the transporters that absorb sodium and glucose, but this has not be studied in the horse. When sodium and glucose are not absorbed, water remains in the intestine and the horse develops diarrhea. It is important to understand the cellular mechanisms behind C. diff diarrhea in the horse as this will lead to development of targeted treatments.
RESEARCHER: Dr. Breanna Sheahan, North Carolina State University
RESEARCH PROJECT: Equine placentitis in the lab: an organoid model
Each year, several mares are affected by a condition called placentitis, which is an infection and inflammation of the placenta. The placenta is the cradle of every new life, critical for all aspects of pregnancy for both foal and mare. Therefore, when the placenta becomes infected, it can have severe consequences. Placentitis can lead to abortion, premature birth, stillbirth, delivery of a compromised foal, increased perinatal mortality, and reduced future fertility in the mare. Beyond the health and welfare impacts on the animals, placentitis causes emotional distress to owners, and results in multimillion-dollar losses in the equine breeding industry. Placentitis is typically caused by bacteria, particularly Streptococcus equi subspecies zooepidemicus (Strep. equi), that ascend the reproductive tract from the outside.
Despite the importance of this disease, the exact underlying mechanisms are not fully understood, leading to inefficient preventive, diagnostic, and treatment protocols. Currently, our understanding is limited to experimentally induced cases of placentitis or clinical cases, both of which limit our investigation by providing only a snapshot of the condition at the time of sample collection and are typically after the detection of clinical signs, bypassing the initial stages of the disease. To address this gap, we propose studying the interaction of Strep. equi with placental organoids, also known as mini placentas in the lab. Organoids are three-dimensional (3D) cell cultures that more accurately represent the original organ compared to traditional two-dimensional (2D) cell cultures. Our group, for the first time, has successfully developed equine placental organoids that mimic the structure, function, and molecular characteristics of the mare’s placenta. By infecting these organoids with Strep. equi, we aim to create an equine placentitis model. Once established, we can use this model to identify the initial interactions between Strep. equi and the placenta and study the progress of the disease without using live animals. We believe this research will lead to better understanding, diagnosis, and treatment of placentitis, ultimately benefiting the health and welfare of mares and their foals.
RESEARCHER: Dr. Pouya Dini, University of California, Davis
RESEARCH PROJECT: A Final Validation of the Equine Exfoliome for Colic
Gastrointestinal (GI) disease, particularly colic, accounts for over 20% of equine deaths, making it a significant welfare and economic issue. Despite advances in diagnosing and managing colic, research has primarily focused on treatment rather than prevention. There is need for a paradigm shift towards prevention, necessitating a deeper understanding of the causes of colic, especially the unclear functional disturbances potentially linked to microbiomic changes. Our collaborative group has developed a technique to study gene expression in cells shed in horse feces, termed the exfoliome. We have generated multiple manuscripts describing this approach and its potential impact. However, this technique has not yet been compared to the gene expression profile of tissues from multiple regions of the GI tract in horses with GI disease. This proposal aims to acquire the final data needed to validate this method by comparing the gene expression profiles from various GI tract tissues with the exfoliome in horses with NSAID-induced GI injury. Using archived samples from thoroughly characterized horses, we seek to enhance our understanding of equine GI diseases and develop effective prevention strategies.
RESEARCHER: Dr. Canaan Whitfield-Cargile, University of Georgia