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Kathryn Meurs

Dean - Veterinary Medicine

CVM Main Building A229

Bio

Dr. Meurs completed her DVM at the University of Wisconsin – Madison and completed a small animal internship at North Carolina State University. She completed a Cardiology residency at Texas A&M University and is board certified from the American College of Veterinary Internal Medicine (Cardiology). Dr. Meurs has a Ph.D. in Genetics from Texas A&M University and her areas of interest include familial aspects of cardiovascular disease, especially cardiomyopathy.

 

Area(s) of Expertise

Genetics, Spontaneous Animal Disease Models, Genetics of Cardiovascular Disease

Publications

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Grants

Date: 09/20/21 - 9/30/24
Amount: $6,277,542.00
Funding Agencies: National Institutes of Health (NIH)

The overall goal of this project is to design, construct and outfit a swine biomedical research facility on the campus of the fourth ranked College of Veterinary Medicine in the United States with ready access to trained veterinary specialists and state of the art biomedical (e.g. MRI, CT and nuclear medicine) facilities. The facility will provide additional high-quality space for biomedical research by NIH funded faculty from NC State University, Duke University and the University of North Carolina. The design and construction of the swine biomedical research facility will feature a free-standing masonry and steel building that will house the production and care of gnotobiotic and gene-edited swine, as well as state-of-the-art procedures (surgical, telemetry, arthroscopy, endoscopy). In addition, the unit includes flexible space that can accommodate pregnant and non-pregnant sows, and farrowing facilities to generate needed gene edited progeny from our own lines as well as those obtained from the NIH-supported NSRRC. Procedural space will provide a sterile surgery suite (two tables) to accommodate an increasing bioengineering need for endoscopic and arthroscopic procedures. The building will be placed immediately adjacent to space (referred to as the G20 facility) previously created for the use of severe combined immunodeficiency and other gene edited miniature or juvenile pigs (G20 OD020279) to allow for shared use of the space when possible. The proposed facility has been designed to maximize synergy and minimize overlap with the G20 space. Combined they will give us a high degree of flexibility and will allow us to conduct a broad range of research thus having a broad impact across multiple NIH Centers/Institutes. This project team is uniquely situated to drive the design and development of this facility and the expansion of this program. By serving in leadership roles within the College of Veterinary Medicine and NC State University we have the ability to provide access to the veterinary college biomedical campus, the research animal facilities and the state-of-the-art equipment in the tertiary care veterinary hospital. Our team of investigators has comparative medicine expertise and an extensive collaborative network with biomedical researchers at Duke and the University of North Carolina. As a team, we have successfully managed infrastructure grants, such as the expansion of facilities for housing and studying transgenic and non-transgenic miniature pigs (G20 OD020279) and building projects including a 20,000 square foot wet lab and GMP lab space.

Date: 01/01/23 - 12/31/23
Amount: $348,032.00
Funding Agencies: Zoetis, LLC

Study Development - Zoetis

Date: 08/01/18 - 7/31/23
Amount: $2,945,825.00
Funding Agencies: National Institutes of Health (NIH)

The National Research Council has documented a dire national need for veterinary specialists trained in biomedical research. Furthermore, veterinary researchers play a key role in comparative and translational research activities since they naturally bridge basic and clinical research. To address this training need, we request continued NIH funding for 7 fellows per year for 3 years. NC State University will provide funding for up to 2 fellows per year and 2 pre-T32 positions. Trainees will be degree-seeking fellows in the Comparative Medicine and Translational Research training program established by the faculty in the College of Veterinary Medicine (CVM) and the Comparative Medicine Institute (CMI) at North Carolina State University. This training program specifically targets individuals with the DVM degree who have completed specialty training and is designed to prepare trainees to compete for an early career development award and a rapid transition to independence as a principal investigator or in another research-intensive career. Trainees complete requirements leading to the PhD degree in Comparative Biomedical Sciences (CBS) in one of 7 areas of oncentration: 1) Immunology 2) CellBiology, 3) Pharmacology, 4) Neurosciences, 5) Infectious Diseases, 6) Population Medicine, and 7) Pathology. Training faculty are well-funded productive scientists that have a strong training track-record and diverse research expertise. Training faculty are all members of the CBS graduate program and the CMI and represent 4 departments from 2 Colleges. Research projects emphasize comparative and translational themes fostered by the CVM and CMI in tissue engineering, pharmacology and physiology, genetics and genomics, and emerging infectious diseases. Program requirements include: (1) a capstone comparative medicine and translational research seminar course; (2) professional development courses and workshops; (3) a course in research ethics; (4) a grant writing course and a pilot grant program that provide a pathway to a K award; and (5) annual research symposia. These requirements are in addition to those associated with the graduate program. Sixteen fellows have completed training. Thirteen hold faculty positions in academia, one is a research pathologist, and two are research fellows at other institutions. Fellows were awarded 7 NIH or other career development grants and 15 extramural research grants and published 67 papers (48 first author) arising from their research while in training.

Date: 07/01/21 - 6/30/23
Amount: $242,055.00
Funding Agencies: Nippon Zenyaku Kogyo Co., LTD. (ZENOAQ)

Study to Investigate Treatment for Canine Atopic Dermatitis in clinical cases in the dog. Patients from the North Carolina region will be recruited.

Date: 01/31/21 - 11/30/22
Amount: $70,986.00
Funding Agencies: Scout Bio, Inc.

This is a clinical field effectiveness and safety study in client-owned cats diagnosed with DM. This is a multi-site, placebo-controlled, randomized, double blinded field trial comparing the rate of diabetic remission in naïve and previously treated diabetic cats when treated with SB-009 + insulin or placebo + insulin. It is expected that 60 evaluable cases will be enrolled with approximately 30 cats randomly assigned to either treatment (IVP, SB-009) or control (CP, placebo). The cats will be evaluated by a veterinarian at the following visits: screening (7 to 2 days before Day 0), Day 0, Day 7 (telephone contact to check status), Day 14, Day 28, Day 42, Day 56, Day 70, Day 84, Day 112, Day 140, Day 168, and Day 196. On Day 0 Cats will received a single injection of IVP or CP. All cats will continue to receive daily insulin until the cat is determined to be in remission, at which point administration of insulin will stop. Daily insulin may be started again if at any point it is determined the cat has fallen out of remission. The effectiveness will be measured by comparing the percent of cats entering diabetic remission in 6 months.

Date: 08/11/20 - 10/31/22
Amount: $83,146.00
Funding Agencies: TriviumVet

Rapamycin is a specific inhibitor of the mechanistic target of rapamycin complex I (mTORC1) protein complex, which acts as a central regulator of cell growth and nutrient response. It has been used extensively in clinical medicine in humans, principally to prevent the rejection of organ transplants. Experimental evidence suggests that mTORC1 inhibition is associated with a number of beneficial cardiovascular effects, including reducing cardiac hypertrophy and improving cardiac function in the presence of pressure overload and genetic cardiomyopathies, reducing ischemic injury after acute and chronic myocardial infarction, and the reactivating cardiac autophagy. Researchers suggest that these effects are likely dependent on the fact that partial inhibition of mTORC1 abolishes the detrimental effects of mTORC1’s maladaptive functions during cardiac stress, while still maintaining its physiological functions. Treatment with rapamycin has been shown to improve markers of cardiac health and function in dogs, rodents, and humans. The present study will be the first to evaluate the potential of the drug to reverse or delay the progression of the pathology observed in cats with naturally occurring HCM. Results from an ongoing toxicokinetic study in healthy laboratory cats will be shared with the investigators before this study commences, and a summary of the findings will be provided in a client information brochure to participating centers.

Date: 07/01/19 - 6/30/22
Amount: $134,750.00
Funding Agencies: V Foundation for Cancer Research

This study addresses two important challenges related to the development of neoantigen vaccine approaches for treating T-cell lymphoma. The first is quantitative: effective vaccination must elicit anti-tumor effectors in numbers equivalent to those generated in natural infections in order to outpace cancer progression. The second challenge is the negative role that the tumor physiologic microenvironment might play in negatively regulating such immune reactivity, leading to vaccine failure. Peripheral T-cell lymphomas (PTCL) are a group of heterogeneous, clinically aggressive malignancies that are refractory to traditional chemotherapy agents and associated with a poor outcome. Survival with standardof-care CHOP therapy is <8 months.(1, 2) The persistence of a tiny population of chemoresistant malignant cells – called minimal residual disease, or MRD – demonstrable by sensitive molecular assays during treatment is thought to be the source of relapse and treatment failure. New chemotherapy agents and small molecule inhibitors have entered the picture, yet outcomes remain stubbornly inferior to those with B-cell tumors.(3, 4) Eradicating MRD via immunotherapy to improve PTCL outcomes and effect cures is a tantalizing possibility. However, trials in PTCL using monoclonal antibodies (Abs) or chimeric antigen receptor T cells targeting various T-cell surface markers have only had limited successes.(5) In solid tumors, immune checkpoint blockade has been shown to elicit T-cell responses directed against tumor-specific neoantigens, which can exert clinically meaningful effects.(6) Recently, neoantigen vaccination in melanoma has also been shown to be an effective, direct means to raise such anti-tumor immune responses.(7, 8) In spite of the strong rationale and some success in treating solid tumors, though, targeting neoantigens to eradicate MRD in PTCL is not well-explored. As non-germline-encoded proteins, neoantigens are attractive mmunotherapy targets because the corresponding (cognate) T-cell repertoire has not been subject to central deletional tolerance, and high-avidity (strongly reactive) effectors are recruitable. Despite this advantage, clinical responses to immune checkpoint blockade are not universal, and success rates vary. In fact, for most tumor types, responding patients are the minority. One mechanism underlying these differential responses is neoantigen availability, which reflects the somatic mutation rate of the tumor; lymphomas, for example, usually have few mutations and are immunologically “cold”. Another important cause for the failure of neoantigen-targeted immunotherapy is that T cells in the tumor physiologic microenvironment must operate under harsh, unfavorable conditions, characterized by hypoxia, acidosis and lactate accumulation, which can inhibit effector functions.(9, 10). In PTCL, the situation is potentially more dire, since malignant lymphocytes occupy secondary lymphoid tissues, competing for and depleting nutrients needed by anti-tumor T cells for optimal activation and proliferation.(11) Robust antigen-driven T-cell expansion is vital for effective immunity, and increasingly, it’s been recognized that T-cell quantity, not just quality, is a critical determinant of the success or failure of cancer vaccines. Objective responses against tumors are only produced with a massive expansion of the cognate T-cell population to levels rivaling those achieved in viral infections. Characterizing the lymphoid microenvironment in PTCL to determine its ability to support the high metabolic demands of such T-cell proliferation is essential for developing effective strategies for neoantigen vaccination. Our preliminary data examining MRD in canine PTCL, a model of human PTCL, shows that patients always have readily detectable circulating cancer clones, despite induction of complete remission (CR). Our hypothesis is that these malignant cells, trafficking through and proliferating in lymph nodes, continue to cause significant metabolic derangements hostile to T-cell responses to vaccinat

Date: 05/01/20 - 4/30/22
Amount: $115,474.00
Funding Agencies: American Kennel Club Canine Health Foundation, Inc.

Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) is an inherited heart disease diagnosed most commonly in the Boxer dog. We previously identified the first known causative mutation for ARVC in the dog in the striatin gene. However, this mutation does not explain all affected canine cases. As in the human form of ARVC, there appears to be more than one cause of familial ARVC in the Boxer. To identify a second causative variant, we have collected DNA samples from 20 Boxer dogs with confirmed Boxer ARVC that are negative for the striatin mutation and we are proposing a whole genome sequencing approach to find the second cause. We previously used a similar approach to successfully identify a second causative mutation for dilated cardiomyopathy in the Doberman pinscher. Here, we propose to identify the second genetic variant that leads to the development of ARVC in the Boxer dog. Ultimately, we will use this information to improve our understanding of the pathophysiology of ARVC, to help us improve treatment modalities and to use this information to develop a strategy to gradually reduce the prevalence of the additional variant and the disease.

Date: 08/01/20 - 4/30/22
Amount: $146,591.00
Funding Agencies: Aniluxx Biotechnology

Dogs: mix of gender and breeds and between 7 months and 5 years of age, of any breed or sex and in general good health other than allergic dermatitis Number of Dogs: will be depend on cost but no more than 5 per group or 15 in total Active: Hydrocortisone butyrate Dosing regimen: Daily (or twice daily?) to affected areas for 7 (or 14) days (stop treatment when resolves – LOCF analysis) Application rate: 10 mg per cm2 of affected area Owner application; Owner is likely to need to apply daily and will need to be trained. No Maximum application area: - Weigh product before and at the conclusion to determine useage Safety Measurements: Complete blood count and biochemistry will check general health of dog. Blood sampled at initiation and conclusion. QoL questionnaire of dog prior to treatment –As per QOL questionnaire Favrot et al 2010 Vet Dermatology 21 64-70. QoL done at initiation and conclusion. This questionnaire covers all the major elements of behavior related to atopy including scratching, activity, lethargy etc. Owner log of behavior to document any further systemic issues such as eating, drinking, fever, side effects of the medication etc. Efficacy Measurements: Visits to Dermatologist on Day 0 and 7 (and 14?). Ease of application – questionnaire to owner of ease of application Criteria for improvement • Change in Canine Atopic Dermatitis Extent and Severity Index (CADESI)-4. • VAS Measure pruritic scores

Date: 03/15/19 - 1/31/22
Amount: $63,105.00
Funding Agencies: American Kennel Club Canine Health Foundation, Inc.

Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) in the Boxer dog is an adult onset, familial disease characterized by the presence of ventricular arrhythmias, fainting and sudden death. We identified a causative mutation in the cardiac Striatin gene that is highly associated with the development of Boxer ARVC. We have demonstrated that some Boxer dogs with the mutation have a more severe form of the disease and will become quite sick while others will remain free of clinical signs. The reason for the variability in clinical signs is unknown but is thought to be associated with concurrent factors for that individual dog which could include a role for chronic infections, as well as genetics, hormonal levels, or other external factors including diet or exercise. The range of disease manifestation of Bartonella infection in dogs is broad, but Bartonella has been shown to infiltrate the heart muscle and has been identified in human beings with ARVC. We hypothesize that chronic Bartonella spp. infection may lead to the development of the more severe form of Boxer ARVC. Understanding the role of this, and other infectious diseases in the severity of ARVC will greatly improve the ability to manage this common and sometimes fatal heart disease.


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