Samuel Jones

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 concentration: 1) Immunology 2) Cell Biology, 3) Pharmacology, 4) Neurosciences, 5) Infectious Diseases, 6) Population Medicine and Global Health, 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 5 departments from 3 Colleges. Research projects emphasize comparative and translational themes fostered by the CVM and CMI in functional tissue engineering, translational pharmacology and physiology, and emerging and infectious diseases. Program requirements include: (1) a capstone comparative animal models course; (2) professional development courses and workshops; (3) courses in research ethics and research rigor and reproducibility; (4) a grant writing course and (5) annual research symposia. These requirements are in addition to those associated with the graduate program. Twenty four fellows have completed training. Twenty hold faculty positions in academia, one is a research pathologist, one is a clinical pathologist in industry, and one is a postdoctoral fellow. Fellows were awarded 18 NIH or other federal grants as PI and more than 50 extramural research grants and published 125 papers (84 first author) arising from their research while in training.

The majority of students entering the DVM program do so largely because of interests related to private practice. Providing veterinary students with positive experiences in research early in their curriculum is likely to encourage students to consider a career as a clinician-scientist. The objective of the North Carolina State University & Boehringer Ingelheim Veterinary Scholar Program is to provide DVM students with supportive mentored research experiences in biomedical laboratories located within our College of Veterinary Medicine. The NC State College of Veterinary Medicine has developed a portfolio of research training opportunities for veterinary students and veterinarians. All of these are integrated to some degree, but those that interface with the Veterinary Scholars Program (VSP) Summer Research Internship (which includes the Boehringer Ingelheim Veterinary Scholars, Morris Animal Foundation Veterinary Student Scholars, AVMA/AVMF Student Scholars, Resnick Fellows, and CMI Fellows) are the Combined DVM/PhD Program and ORIP funded T35 Interdisciplinary Biomedical Research Training Program designed to provide continued research training beyond the VSP Summer Research Internship. Touch points between these programs include the seminar series held during the summers attended by students in all 3 programs, the National Veterinary Scholars Symposium attended by students in all 3 programs, poster and oral presentations during our Spring CVM Research Forum during which students from all 3 programs present their work, informal interactions in class, laboratories, and other activities.

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 multidisciplinary and interdisciplinary research activities since they naturally bridge basic and clinical research. To address this training need, faculty in the North Carolina State University College of Veterinary Medicine (CVM) established the Interdisciplinary Biomedical Research Training Program (IBRTP) for veterinary students in 2009. The objective of this training program is to provide interdisciplinary biomedical research experience specifically targeted to veterinary students with a strong interest in a research career. The training program also serves as a bridge to foster new interdisciplinary research collaborations amongst faculty members. Trainees complete a 3-month research experience in the laboratories of faculty members drawn from nine different disciplines. Trainees are mentored by two faculty members from different disciplines to create and execute an interdisciplinary project. The 29 faculty members participating in this program are well funded and have a strong training track record. The nine disciplines selected are areas of strength at NC State; Clinical Sciences, Cellular and Molecular Biology, Genetics and Genomics, Engineering, Food Safety, Statistics, Pharmacology, Regenerative Medicine, and Toxicology. Research projects emphasize the melding of two disciplines to create a novel approach to a biomedical research problem. Projects combining clinical and basic science disciplines are given priority. Trainees will be veterinary students in their first or second year who are building on prior research experience. The training program started in 2009 with funds committed by NC State University CVM. Four trainee slots funded by the NIH were added in 2010. The number of NIH supported trainee slots grew to 7 in 2012. To date, a total of 22 NIH funded trainees have completed the program. We propose in this renewal application that the number of NIH funded training slots be increased to 10 per year. Program requirements include: (1) a weekly seminar series on topics related to research ethics and scientific and professional development; (2) a weekly journal club discussing interdisciplinary research papers; (3) participation in the NIH-Merial National Veterinary Scholars Symposium and the annual CVM research symposium. These requirements are in addition to those associated with a student������������������s research training experience.

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 multidisciplinary and interdisciplinary research activities since they naturally bridge basic and clinical research. To address this training need, faculty in the North Carolina State University College of Veterinary Medicine (CVM) established the Interdisciplinary Biomedical Research Training Program (IBRTP) for veterinary students in 2009. The objective of this training program is to provide interdisciplinary biomedical research experience specifically targeted to veterinary students with a strong interest in a research career. The training program also serves as a bridge to foster new interdisciplinary research collaborations amongst faculty members. Trainees complete a 3-month research experience in the laboratories of faculty members drawn from nine different disciplines. Trainees are mentored by two faculty members from different disciplines to create and execute an interdisciplinary project. The 29 faculty members participating in this program are well funded and have a strong training track record. The nine disciplines selected are areas of strength at NC State; Clinical Sciences, Cellular and Molecular Biology, Genetics and Genomics, Engineering, Food Safety, Statistics, Pharmacology, Regenerative Medicine, and Toxicology. Research projects emphasize the melding of two disciplines to create a novel approach to a biomedical research problem. Projects combining clinical and basic science disciplines are given priority. Trainees will be veterinary students in their first or second year who are building on prior research experience. The training program started in 2009 with funds committed by NC State University CVM. Four trainee slots funded by the NIH were added in 2010. The number of NIH supported trainee slots grew to 7 in 2012. To date, a total of 22 NIH funded trainees have completed the program. We propose in this renewal application that the number of NIH funded training slots be increased to 10 per year. Program requirements include: (1) a weekly seminar series on topics related to research ethics and scientific and professional development; (2) a weekly journal club discussing interdisciplinary research papers; (3) participation in the NIH-Merial National Veterinary Scholars Symposium and the annual CVM research symposium. These requirements are in addition to those associated with a student������������������s research training experience.

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.

Environmental pollutants pose an incredible threat to animal and human health. Found ubiquitously in our daily lives and across the globe, individuals are exposed to these pollutants throughout their lives. They impact health at all stages of life, from in utero congenital defects to early childhood developmental defects and to the increased incidence and progression of chronic adult disease. Developmental toxicity is of particular interest in vertebrate models, since many of these pathways are contaminant targets and are highly conserved across vertebrate species (Leung et al. 2017). Most, if not all this work has come down to how contaminants interact with molecular pathways ������������������ what endogenous compound they mimic, what receptors they bind to, how they affect the amount of a certain product, etc. However, understanding these mechanisms is not enough to predict development in response to toxic exposures. Many of these contaminants have variable impact on individuals, which again is largely determined by genetic factors. This project proposes to answer some of the questions surrounding genetic effects on environmental exposures, better known as gene-environment interactions (G x E) using a unique model: a wild-derived inbred Kiyosu panel of medaka (Japanese rice-paddy) fish. Our partners have formed a panel consisting of over 100 inbred lines from this wild population and mapped out each of their genomes. As a multi-disciplinary, international collaboration we will be screening 10 environmental contaminants (chosen for impact and chemical diversity) with multiple early developmental, high dimensional, quantitative measurements on cardiac physiology, cardiac development and skeletal development, the latter of which I will be focusing.

A major risk factor in the vulnerability to immune disorders is biological sex. In some of the most prevalent immune disorders such as allergy/anaphylaxis, autoimmune disease, and chronic pain disorders, females are at increased risk. Adult sex hormones, such as estrogen, may explain some of the sex differences; however,this is challenged by the fact that many immune disorders exhibit a sex bias in prepubertal children. Our recent published and preliminary studies have uncovered sex differences in the mast cell that may explain female vulnerability or male resilience to many immune disorders. Mast cells are innate immune cells that act as effector cells and orchestrators of the immune response. The fact that many mast cell-associated disorders (allergy, autoimmune disease, chronic pain disorders, irritable bowel syndrome) exhibit a sex bias in both childhood and adulthood positions the mast cell as a novel regulator of sex differences in immune diseases. Specifically, we have shown that female mast cells possess an increased capacity to synthesize, store and release potent mast cell mediators including histamine, serotonin, proteases, etc. In animal models of IgEmediated anaphylaxis and psychological stress, female animals exhibited enhanced release of mast cell mediators and more severe pathophysiologic and clinical disease, similar to findings in humans. Moreover, our recent preliminary data demonstrates that sex differences in mast cells emerge early in life prior to puberty and thus may explain sex differences observed in children. The components of sexual differentiation that impact the mast cell phenotype and consequently increase female vulnerability to immune disorders is unknown. Based on preliminary data, we hypothesize that sex differences in mast cell phenotype and immune-related disease susceptibility are established early in life by perinatal androgens. In this F30 proposal, we aim to establish the role of perinatal androgens in determining sex differences in the mast cell and susceptibility/resiliency to later life immune pathophysiology in immunological and psychological stress models. Toward this goal, by conducting perinatal androgenization experiments in mice we will 1) identify the contribution of perinatal androgens in mast cell disease susceptibility and 2) determine the contribution of perinatal androgens in mast cell phenotype, function, and gene expression patterns. The exploratory studies proposed in the grant application will represent a major paradigm shift in the understanding of sex and mast cell-related immune disorders.

The goal of this project is to obtain proof of principle data to establish MARCKS inhibition as a viable therapeutic strategy for the treatment of equine asthma. We hypothesize that the MARCKS protein plays a key role in the inflammatory response in the lungs of horses with asthma and that inhibition of the MARCKS protein with the MANS peptide will diminish the in vitro inflammatory response of equine pulmonary cells from asthmatic horses. Objective 1: Determine whether MARCKS protein expression and/or phosphorylation is upregulated in BAL-isolated pulmonary cells of horses with mild/moderate (n=6) or severe (n=6) asthma vs. healthy horses (n=6). Asthma severity will be classified by clinical signs and BAL cytology[4]. Objective 2: Determine the effect of MARCKS inhibition (with the MANS peptide) on the in vitro cytokine response and respiratory burst of antigen stimulated pulmonary cells. The effect of MANS peptide treatment both before, and after, antigen stimulation will be evaluated.

Alzheimer������������������s Disease is characterized by the accumulation of extracellular beta-amyloid plaques and intracellular neurofibrillary tangles of tau protein. Scientists do not know exactly what role these plaques and tangles play in contributing to AD, but they are associated with increased destruction of nerve cells in patients with the disease, leading to memory loss and behavioral changes.iii To study AD and the pathological process of neurodegeneration, most researchers use transgenic mouse models. With genetic manipulation, scientists can induce the deposition of beta-amyloid plaque in mouse brains, similar to the deposition in human AD patients. However, the biochemical composition of the beta-amyloid plaque is different in mice and humans, and mice do not develop the neurofibrillary tangles associated with human AD.iv Another major limitation of transgenic mouse models for AD is that the progressive neuronal loss in the hippocampus and neocortical regions of the brain that is characteristic of the human condition does not occur in mice.v No mouse model can fully reproduce the disease progression of AD patients, so the need for a better animal disease model is significant.

The goals of the Veterinary Scholars Program at North Carolina State University are to promote advanced study, research, and other scholarly activities of veterinary students, to encourage students to consider careers in academic or industrial veterinary medicine or comparative biomedical research; to enrich the foundation of veterinary practice with scientific principles, evidence based decision making, and problem solving skills; and provide opportunities for mentored research experience. The College of Veterinary Medicine is pleased to offer a Summer Research Internship Program to first and second year DVM students. In the program, veterinary students have the opportunity to spend the summer doing mentored clinical or basic science research in any of a number of biomedical laboratories located within our College of Veterinary Medicine. This program is sponsored by Merial (now Boehringer Ingelheim), the Fund for Discovery, the Comparative Medicine Institute, NC Veterinary Medical Foundation Fund for Discovery, and the Office of the Associate Dean for Research. The program provides a stipend to support the student������������������s research activities with a faculty mentor who directs the research. In addition to the mentored research activities, the program will includes a seminar series, a trip to a biomedical research institute or company in the triangle (such as the NIEHS or EPA), and a mini-research forum at the end of the summer for students in the program to share their work. All students entering this program are eligible to attend the Boehringer Ingelheim Veterinary Scholars Program Symposium held yearly at the end of the summer at various participating Veterinary Schools. Students will meet peers from other institutions, present their work during poster sessions, and hear presentations from nationally recognized speakers. An information session explaining the program and introducing mentors to prospective students will be held in mid to late October. Applications will be due in early February.