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Title

Adjunct Faculty

Office Building

Animal Disease Research and Diagnostic Laboratory

Office

105

Mailing Address

Animal Disease Research 105
Animal Disease Research-Box 2175
University Station
Brookings, SD 57007

Education

• B.S. in textile science (honors) | South Dakota State University | 1991
• M.S. | University of Tennessee, Knoxville | 1997
• DVM (honors) | Colorado State University | 2013
• Residency in veterinary anatomic pathology | Colorado State University | 2016
• Diplomate | American College of Veterinary Pathologist | 2018
• Ph.D. Candidate | Colorado State University

Academic Interests

• Translational medicine
• Pulmonary vascular biology
• Cardiopulmonary pathology
• Obesity-induced pulmonary hypertension on left heart disease
• Epicardial adipose tissue as a risk factor for adverse cardiac events and therapeutic target
• Adaptations to environmental hypoxia

Academic Responsibilities

• Diagnostic pathology
• Investigative pathology and research

Committees and Professional Memberships

Committees

• Yukon Quest International Sled Dog Race
  • Race veterinarian for the 300 and 1,000 mile races.
  • Race pathologist.
• Peer-Reviewed Articles for Pulmonary Circulation

Professional Memberships

• Pulmonary Vascular Research Institute (PVRI)
• National Cattleman’s Beef Association (NCBA)
• American Angus Association, Lifetime Member
• Aberdeen Angus Society
• Academy of Veterinary Consultants (AVC)International Sled Dog Veterinary Medicine Association (ISDVMA)
• American Association of Veterinary Laboratory Diagnosticians (AAVLD)
• American College of Veterinary Pathologists (ACVP)

Awards and Honors

• 2018, Dr. Bob Tombs Scholarship
• 2018, Mark Gearhart Memorial Scholarship
• 2017, ATS Fellows Track Symposium Award
• 2017, Pattridge Family Scholarship
• 2017, 18th CSU CVMBS Research Day 3rd Place Oral Presentation, Clinical Sciences
• 2016, NCBA, WD Farr Scholar
• 2016, Mortimer, Beef Today, Elanco Scholarships
• 2015, CSU Veterinary Specialty Resident of the Year
• 2014, Mortimer, Beef Today, Elanco Scholarships
• 2014, CSU Veterinary Specialty Resident of the Year
• 2010, Thomas Spurgeon Book Award Given to CSU First Year Veterinary Student
• 2009, William Inskeep II Pathology Scholarship

Grants

• Metabolism and Inflammation Predict Cardiovascular Disease Outcomes in Fattened Beef Cattle. USDA NIFA, July 3, 2018, $499,772.

Patents

U.S. Patent No. 6,197,709
Meltbown composites and uses thereof.
Inventors: Peter Ping-Yi Tsai, Knoxville, Tennessee; Charles B. Hassenboehler, Knoxville, Tennessee; Larry C. Wadsworth, Knoxville, Tennessee; Greta Heismeyer, Lenoir City, Tennessee 
Assignee: The University of Tennessee Research Corporation, Knoxville, Tennessee 
Granted: September 1998

Work Experience

• 2013-present, Hypobaric Hypoxic Chamber Neonatal Calf Study director

Areas of Research

I seek to use my veterinary training and specialty certification in veterinary anatomic pathology to cultivate my interests in pulmonary vascular biology and cardiovascular pathology as they apply to the development of a translationally-relevant pre-clinical large animal model of pulmonary hypertension on left heart disease (LHD, WHO Group 2 PH). Mechanistic insight gained from the development of a large animal model of PH on LHD has the added benefit of adding to our knowledge of the condition in beef cattle. For reasons that are poorly understood, a subset of cattle in response to industry feeding and fattening regimens develop congestive heart failure (CHF) with evidence of global cardiac and pulmonary remodeling leading to PH and right heart failure (RHF). Bovine CHF is an important cause of mortality in North American feedyards, and independent of mortality, the condition negatively impacts productivity and carcass traits. There is an unmet need for biomarkers predictive of disease that can be used to assess risk and inform management decisions pertaining to beef cattle entering feeding programs. My research proposes to bridge the gap between basic science and clinical trials in Group 2 PH-LHD patients with the added benefit of developing a mechanistic understanding of bovine CHF,  informing the industry on how best to mitigate the impact of bovine CHF, enhance cattle health and welfare and improve sustainability of beef production. This can only be achieved in an environment that supports an integrative, multidisciplinary One Health approach to optimizing human health and the health of the production animal species that sustain global protein requirements.

To this end, my extensive training as a T32 postdoctoral fellow under the mentorship of Kurt Stenmark, MD in the Cardiovascular Pulmonary Research Lab, UC Denver Anschutz School of Medicine has enhanced my understanding of the complex, multistep pathophysiology of pulmonary vascular remodeling in the setting of environmental hypoxia, chronic lung disease (WHO Group 3) and left ventricular dysfunction and valvular diseases (WHO Group 2). I have actively participated in disease modeling, experimental design and in vivo assessment of cardiopulmonary function in both neonate and adult cattle, performing right heart catheterizations in controlled experimental and field settings and participated in interventional studies. My veterinary training has proved advantageous in the mitigation of enteric and respiratory diseases that commonly plague calves in the neonatal period, improving experimental outcomes and data integrity. The nature of the work facilitates interactions with pediatric and adult pulmonary pathologists, transplant pathologists, cardiologists, surgeons, emergency and critical care physicians and researchers committed to basic scientific and pre-clinical research in the fields of molecular cardiology, metabolomics, macrophage biology, immunology and bioengineering. The intersection of these specialties with veterinary medicine is but one example of the boundless opportunities for collaborations between the human medical and veterinary disciplines prerequisite to advancing our mechanistic understanding of human and animal cardiopulmonary diseases, identifying potential therapeutic targets and testing interventional therapies. It is my belief that T32 training has developed my comprehension of pulmonary vascular disease, cardiovascular pathology and adipose tissue biology beyond the applied sciences cultivated during my veterinary and pathology training. Further, these collaborative efforts have expanded my familiarity and experience with state-of-the-art technologies used to perform rigorous quantitative analysis of cardiopulmonary remodeling, high throughput omics technologies for screening large numbers of samples for the discovery and validation of candidate biomarkers predictive of disease, and second harmonic generation microscopy coupled with two-photon excited immunofluorescence to assess cardiac fibrosis, among others. Dr. Stenmark advanced my understanding of bovine pulmonary anatomy, intrapulmonary shunting and microvessel disease in bovine CHF and other forms of parenchymal lung disease by challenging me to investigate and describe structural-functional alterations similarly identified in the human condition. Thanks to Dr. Stenmark, I confirmed the presence of myocardial sleeves on the extrapulmonary segments of the bovine pulmonary veins, although their role in the regulation of blood flow to the heart remains enigmatic. Further, it appears that obstructive lesions in the pulmonary arterial circulation gives rise to intrapulmonary shunting between pulmonary and bronchial arteries and pulmonary arteries and veins. Our analysis of arterial-venous blood gas samples supports this assertion. In-vivo and ex-vivo three-dimensional reconstruction of bovine pulmonary blood flow is necessary to address these gaps in our knowledge and directs my future research ambitions.

Translationally Relevant Large Animal Model of Obesity-Induce PH on LHD: Group 2 patients represent the largest and fastest growing category of PH patients worldwide and PH as a complication of LHD is prognostically significant with no specific PH-directed therapies. PH-LHD patients often suffer a constellation of comorbid obesity disease burdens as a result of caloric excess and sedentary lifestyle choices. Epic numbers of Americans are experiencing chronic metabolic derangements with attendant pulmonary and cardiovascular complications influencing disease trajectories in PH-LHD patients. Independent of the metabolic perturbations and vasculotoxic effects associated with obesity and the so-called metabolic syndrome (MetS), pathologic expansion of the epicardial adipose tissue (EAT) surrounding the heart is an influential paradigm in the pathophysiology of obesity cardiomyopathy and pulmonary hypertension. A litany of adverse cardiac events can be attributed to unhealthy EAT including impaired contractility, atrial fibrillation, arrhythmias, sudden cardiac death, left ventricular (LV) diastolic dysfunction and coronary artery disease. The plasticity of EAT in response to dietary modification, exercise, bariatric surgery, adiponectomy and targeted pharmacological therapies together with availability of noninvasive imaging modalities to measure EAT volume espouse the tissue’s utility as a cardiac risk factor and interventional therapeutic target. Historically, EAT has been the subject of benign neglect owing to its scarcity in rodent models of cardiovascular disease, safety and ethical concerns raised by acquiring specimens from patients undergoing invasive cardiac procedures and moreover, insufficient quantities of adipose tissue retrieved during biopsy procedures, underscoring the need for larger animal models with more abundant EAT to address knowledge gaps in our understanding of the putative role of EAT in health and cardiopulmonary disease. Given the extent of the obesity crisis in Western society, we can expect a concomitant increase in comorbid metabolic and cardiovascular diseases predisposing to the development of PH. Our mechanistic understanding, identification and validation of therapeutic targets is hampered by the lack of translationally relevant large animal models that recapitulate the complex spectrum of cardiopulmonary lesions and patient heterogeneity in PH with LHD.

Publications

1. Grunig G, Eichstaedt CA, Verweyen J, Durmus N, Saxer S, Krafsur G, Stenmark K, Ulrich S, Grunig E, Pylawka S. Circulating microRNA Markers for Pulmonary Hypertension in Supervised Exercise Intervention and Nightly Oxygen Intervention. Frontiers in Physiology | DOI:10.3389/fphys.2018.00955.
2. Krafsur GM, Neary JM, Garry F, Holt T, Gould DH, Mason GL, Thomas MG, Enns RM, Tuder RM, Heaton MP, Brown RD, Stenmark KR. . Pulmonary Circulation. DOI:10.1177/2045894018796804.
3. M.G. Thomas, J.M. Neary, G. M. Krafsur, T. N. Holt, R. M. Enns, S. E. Speidel, F. B. Garry, A. Canovas, J. F. Medrano, R. D. Brown and K. R. Stenmark. Pulmonary Hypertension (PH) in Beef Cattle: Complicated Threat to Health and Productivity in Multiple Beef Industry Segments. Certified Angus Beef White Papers.
4. Stenmark KR, Krafsur GK, Tudor RM. Pulmonary veno-occlusive disease and pulmonary hypertension in dogs: striking similarities to the human condition. Vet Path 2016; 53:707-710.