Greta Krafsur

Education

PhD Candidate: Colorado State University, Microbiology, Immunology and Pathology
Dissertation: A Large Animal Model of Obesity-Induced Pulmonary Hypertension with Left Heart Disease
Committee: Kurt R. Stenmark, MD; R. Dale Brown, PHD; Gary L. Mason, DVM, PHD, DACVP; Randy Basaraba, DVM,
PHD, DACVP; Franklyn Garry, DVM, MS, DACVIM; Timothy Holt, DVM

Diplomate, American College of Veterinary Pathologists (DACVP) Sept. 2018

Veterinary Anatomic Pathology Residency, Colorado State University 2013-2016

DVM Colorado State University May 2013
With Honors

MSc University of Tennessee, Knoxville Dec. 1997
Thesis: Biodegradable Staple Fiber Nonwovens Calendered with the Assistance of an Aqueous Solvent-Their Fabrication,
Properties and Structural Characteristics
Advisor: Kermit Duckett, PHD

BSc South Dakota State University Dec. 1991
Textile Science, With Honors

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

Committee Activities

Yukon Quest International Sled Dog Race
• Race veterinarian for the 300 and 1,000 mile races
• Race pathologist

Peer-Reviewed Articles for:
• Pulmonary Circulation

Awards and Honors

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

Grants

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

Patents

U.S. Patent Number 6,197,709
Meltbown composites and uses thereof
Inventors: Peter Ping-Yi Tsai, Knoxville, TN; Charles B. Hassenboehler, Knoxville, TN; Larry C. Wadsworth, Knoxville, TN; Greta Heismeyer, Lenoir City TN
Assignee: The University of Tennessee Research Corporation, Knoxville, TN
Granted: September 1998

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)

Work Experience

Cardiopulmonary Adaptations to Environmental Hypoxia:
Hypobaric Hypoxic Chamber Neonatal Calf Study Director 2013-Present
PI: Kurt Stenmark, MD
• Management and husbandry of neonatal Holstein bull calves used in experimental studies observing the effects of 14 day exposure to hypobaric hypoxia at a simulated altitude of 15,500 ft., recapitulating features of WHO Group 3 Pulmonary Hypertension
o Conduct HDAC inhibitor trials in normoxic and hypoxic neonatal Holstein bull calves
o Prevention and treatment of neonatal enteric and respiratory diseases
o Proficient in IV catheterization, right heart catheterization studies, exsanguination and tissue harvest under normoxic and hypoxic conditions
o Development of IUCAC protocols

Publications

Grunig G, Eichstaedt CA, Verneyen J, Durmus N, Saxer S, Krafsur G, Stenmark K, Ulrich S, Grunig E, Pylanka S. Circulating microRNA Markers for Pulmonary Hypertension in Supervised Exercise Intervention and Nightly Oxygen Intervention. Front. Physiol. | doi: 10.3389/fphys.2018.00955.

Area(s) 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.

Applications of Research

Contributions to Science:

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

Krafsur GM, Neary JM, Garry F, Holt T, Gould DH, Mason GL, Thomas MG, Enns RM, Tuder RM, Heaton MP, Brown RD, Stenmark KR. Cardiopulmonary Remodeling in Fattened Beef Cattle: A Naturally Occurring Large Animal Model of Obesity-Associated Pulmonary Hypertension with Left Heart Disease. Pulmonary Circulation. https://doi.org/10.1177/2045894018796804.

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.

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.