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M. Sheats

Asst Professor

DVM, Ph.D, DACVIM

CVM Research Building 390

Bio

Dr. Mary Katherine Sheats (nickname: “Katie”) is an Associate Professor of Equine Primary Care at NC State. Her research focus is on neutrophil mediated diseases that affect horses and humans, including asthma. Dr. Sheats is a native North Carolinian and grew up riding and showing hunter jumpers in the Triad region. She now lives in New Hill, NC with her husband, 2 boys, 10 chickens and 2 retired pleasure horses.

http://www.mksheatsteachingportfolio.com/

AFFILIATIONS

Member, NC State Comparative Medicine Institute, Translational Physiology and Pharmacology
Member, Veterinary Comparative Thoracic Society
Member, Comparative Gastroenterology Society
Member, American Association of Equine Practitioners
Member, One Health Commission
Member, Society of Leukocyte Biology
Member, North Carolina Veterinary Medical Association
Member, American Society for Cell Biology

CERTIFICATIONS

Diplomate, American College of Veterinary Internal Medicine (LA)
Certificate of Reflective Teaching

Area(s) of Expertise

BIOLOGICAL BARRIERS, GLOBAL HEALTH, IMMUNOLOGY, INFECTIOUS DISEASES, SPONTANEOUS ANIMAL DISEASE MODELS

Dr. Sheats's research focuses on the innate immune system and the role neutrophils play in host defense and host injury. Her long term research goal is to identify regulators of the innate immune response and neutrophil function that could serve as targets for new types of anti-inflammatory therapies. Dr. Sheats is currently conducting research to determine whether a host protein known to regulate neutrophil functions is a viable therapeutic target for combating neutrophil-mediated tissue damage during diseases such as asthma and salmonella gastroenteritis. Dr. Sheats's goal is that one day her translational research will benefit both humans and horses.
As a clinician scientist and large animal internal medicine specialist, Dr. Sheats is also interested in clinical research that can help diagnose, treat and prevent disease in horses. Her current clinical interest is to identify new biomarkers of intestinal ischemia in horses with colic. The goal of this research would be to develop a diagnostic tool that could one day help veterinarians accurately identify which horses with colic have intestinal strangulation.
As coordinator of the Equine Primary Care Program, Dr. Sheats is working with equine private practice veterinarians to establish "best practices" for training equine focused veterinary students through a university-private practice partnership. Dr. Sheats is conducting educational studies relevant to veterinary student communication training and competency tracking during distributive preceptorships.

Publications

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Grants

Date: 11/01/22 - 10/31/23
Amount: $37,062.00
Funding Agencies: NC Horse Council

Over the past decade, equine research at North Carolina State University College of Veterinary Medicine (NCSU CVM) has grown exponentially under the leadership of Dr. Paul Lunn (Dean 2012-2022) and Dr. Kate Meurs (Associate Dean for Research and Graduate Studies date 2011- 2022; Dean 2022 - present). At present, our Equine Group is comprised of 16 faculty members with 1 additional search underway and 3 clinical veterinarians (See table below). Each member of our group has an active research program with group funding to date totaling over 45 million dollars. In addition, we are responsible for the training and specialty board certification of 5-6 equine residents/year, each of which must complete a research project of their own, as well as for the training of equine graduate (PhD and MS) students. While our group has been very successful at obtaining external funding (both federal and foundation) for our studies, we have struggled to maintain consistent funding for permanent NCSU CVM equine research herds, which are vital to all facets of our research and clinical work. Full funding for such herds is extremely difficult to fit within the limited budgets of most equine foundation grants. Additionally, funding for these herds is not directly applicable to the budget of many federal grants, whose proposed experiments rely on terminal studies or the use of clinical cases. However, the pilot data for these federal grants, which is absolutely essential for a successful application, does usually come from research herds. Lastly, horses in these herds, and particularly that of Dr. Schnabel’s research herd, are being used to make biologic products that have been highly successful for the treatment of equine hospital patients suffering from infectious arthritis and osteoarthritis as well as other ailments. While hospital revenue from such treatments helps to cover the costs of producing the biologic products themselves, it is not enough to cover the overall care and mandatory screening of these research herd horses for transmissible diseases. In addition to benefiting equine health and translational research, NCSU CVM equine research Herds also provide an important educational opportunity for NCSU students at all levels of training. Between them, Drs. Schnabel, Sheats and the Theriogenology group have trained over 40 undergraduate, 35 veterinary and 12 PhD students in research projects that rely on equine research herds. When appropriate, some of the research horses (Sheats) are also available for use in non-invasive equine science and veterinary teaching labs.

Date: 10/17/22 - 10/16/23
Amount: $20,000.00
Funding Agencies: The Foundation for the Horse

Equine asthma is diagnosed in horses of all breeds and sexes, with mild/moderate EA (mEA) reportedly affecting 60-100% of certain groups of horses, including young racehorses,1,2 and severe EA (sEA) reportedly affecting 10-20% of adult horses in the northern hemisphere.3–5 Characteristic symptoms of both mEA and sEA include recurrent and variable cough and exercise intolerance, with sEA horses showing signs of increased respiratory effort at rest.3–5 These symptoms occur when susceptible horses experience bronchoconstriction, mucus hypersecretion and airway inflammation as a result of exposure to organic dust.3–11 Routine treatments for EA include systemic and inhaled steroids and bronchodilators.12,13 Environmental management that reduces exposure to organic dust, such as increased pasture turn-out and elimination of hay, is the most effective long-term treatment for horses with EA.12,13 Without reduction of dust exposure, horses with sEA experience recurrent disease exacerbation. Unfortunately, elimination of organic dust from a horse’s environment is not always achievable for horse owners, leading to the need for long-term steroid treatment. However, long-term steroid treatment has drawbacks such as expense, if using inhaled medications, or laminitis risk and suppression of the hypothalamic-pituitary axis, if using systemic treatment.14,15 Therefore, alternatives to steroid therapy are needed for horses with EA.

Date: 09/15/22 - 9/14/23
Amount: $6,630.00
Funding Agencies: CytoSorbents

Optimization of Equine Extracorporeal Therapy Protocol

Date: 03/25/22 - 3/31/23
Amount: $38,000.00
Funding Agencies: NCSU Center for Human Health and the Environment

Per- and polyfluoroalkyl substances (PFASs) are used to produce nonstick coatings, food wrappers, and fire-fighting foams. PFASs are environmentally persistent, ubiquitous and can be detected in the serum of 99% of Americans. Despite well-established immunotoxicity, few studies have investigated the effects of PFASs on the innate immune system. We propose combining primary human neutrophils and zebrafish larvae with innovative functional assays to investigate the impact of PFASs on neutrophil function and on the ability to recover from a bacterial infection. Our preliminary data reveal that two PFASs, PFHxA and GenX, suppress the ability of a neutrophil-like cell line to generate reactive oxygen species (ROS). Generation of ROS, along with phagocytosis, are hallmark features of activated neutrophils and play important roles during infection. We have also observed that these PFAS suppress the ability of zebrafish larvae to generate ROS, highlighting the potential of these compounds to negatively impact an organism’s ability to recover from infections. In this proposal, primary human neutrophils will be exposed to PFHxA or GenX and their ability to generate ROS and undergo phagocytosis will be quantified. In addition, zebrafish larvae will be exposed to PFHxA or GenX, infected with a bacterial pathogen, and the bacterial burden quantified. We anticipate that these PFASs will suppress ROS generation and phagocytosis in primary neutrophils, and increase the bacterial burden in infected zebrafish larvae. Successful completion of this project will lay the groundwork for future research on deciphering the cellular and molecular mechanisms by which these PFASs suppress immune function.

Date: 03/22/22 - 3/21/23
Amount: $13,136.00
Funding Agencies: NC Horse Council

Investigating the Impact of Novel Amnion Extracts on Equine Intestinal Epithelial Cell Repair

Date: 09/01/19 - 2/28/23
Amount: $133,865.00
Funding Agencies: US Dept. of Agriculture - National Institute of Food and Agriculture (USDA NIFA)

Non-typhoidal Salmonellae are the leading cause of bacterial foodborne gastroenteritis and bovine food products are frequently implicated in disease outbreaks. The daunting rate of Salmonella infections in humans combined with the increasing number of multiple drug resistant (MDR) isolates is an alarming public health threat. MDR Salmonella infections are frequently traced to bovine sources, making it imperative to design novel, non-antimicrobial strategies to eliminate MDR Salmonella from cattle. In this basic science proposal, we will establish the role of a host-cell protein, MARCKS (Myristoylated Alanine-Rich C-Kinase Substrate), in Salmonella infections. We hypothesize that MARCKS protein function is essential for Salmonella-induced neutrophil recruitment and activation, epithelial invasion, and the overall survival of Salmonella in the host intestine. We will use a MARCKS peptide inhibitor to investigate the role of MARCKS in neutrophil antimicrobial responses in vitro and during calf infection. We will establish the role of MARCKS in Salmonella intestinal invasion in vitro and tissue colonization during calf infection. Finally, we will establish the role of our MARCKS peptide inhibitor on antimicrobial resistance development during calf infection. These experiments will (1) establish the basic biology of MARCKS protein during infection and (2) establish the efficacy of a MARCKS peptide inhibitor as a host-directed therapeutic alternative to treat bovine salmonellosis. Salmonella infections are a threat to both human and bovine health so alternatives to traditional antimicrobials are critically needed to combat this important pathogen. The proposed studies will directly inform development of a non-antimicrobial therapeutic to prevent and treat Salmonella in cattle.

Date: 10/01/20 - 9/30/22
Amount: $15,989.00
Funding Agencies: The Foundation for the Horse

Hypothesis: We hypothesize that upon hospital admission, plasma and/or peritoneal fluid cell-free DNA (cfDNA) will be significantly higher in horses with strangulating or inflammatory colic lesions vs. non-strangulating lesions, horses with SIRS score ≥2 vs. ≤1 (Roy et al. 2017), and/or nonsurvivors vs. survivors. Further, we hypothesize that admission levels of plasma and/or peritoneal fluid cfDNA will be positively correlated with admission levels of serum amyloid A (SAA) and lactate from the same sample type and/or total cost of care. Objective 1: To determine whether plasma cfDNA at hospital admission 1) is significantly higher in horses with strangulating or inflammatory vs. non-strangulating colic lesions, SIRS score ≥2 vs. ≤1, and/or survivors vs. nonsurvivors and 2) is correlated with admission SAA and blood lactate concentrations and hospital invoice. Objective 2a: To determine whether direct and/or diluted peritoneal fluid cfDNA values obtained with the Qubit 4 show a linear correlation to extracted peritoneal fluid cfDNA. Objective 2b: To determine whether peritoneal cfDNA at hospital admission 1) is significantly higher in horses with strangulating or inflammatory vs. non-strangulating colic lesions, SIRS score ≥2 vs. ≤1, and/or survivors vs. nonsurvivors and 2) is correlated with admission peritoneal SAA and peritoneal lactate concentrations and hospital invoice. Results from Objective 2a will be used to determine which type of peritoneal fluid sample to use for cfDNA measurement.

Date: 05/17/21 - 5/16/22
Amount: $10,000.00
Funding Agencies: Foundation for Food and Agriculture Research (FFAR)

This project specifically investigates a novel non-antimicrobial target to combat enteric salmonellosis in cattle. Neutrophils play a key role in Salmonella enteritis, causing inflammation that ultimately enables Salmonella to colonize the gut. In this project, primary bovine neutrophils are used to assess how MARCKS protein (Myristoylated Alanine-Rich C-Kinase Substrate, a host protein known to regulate neutrophil functions) inhibition alters Salmonella-induced neutrophil inflammatory functions, such as adhesion, migration, and respiratory burst. Dr. Katie Sheat’s laboratory is currently conducting research to determine whether this MARCKS protein is a viable therapeutic target for combating neutrophilmediated tissue damage during diseases such as salmonellosis. The goal is that this translational research will benefit both livestock and humans by reducing the morbidity and mortality associated with enteric salmonellosis. Other potential applications of targeting the MARKS protein include the treatment of asthma and COPD across species.

Date: 03/01/18 - 2/28/21
Amount: $455,000.00
Funding Agencies: US Dept. of Agriculture - National Institute of Food and Agriculture (USDA NIFA)

Non-typhoidal Salmonellae are the leading cause of bacterial foodborne gastroenteritis and bovine food products are frequently implicated in disease outbreaks. The daunting rate of Salmonella infections in humans combined with the increasing number of multiple drug resistant (MDR) isolates is an alarming public health threat. MDR Salmonella infections are frequently traced to bovine sources, making it imperative to design novel, non-antimicrobial strategies to eliminate MDR Salmonella from cattle. In this basic science proposal, we will establish the role of a host-cell protein, MARCKS (Myristoylated Alanine-Rich C-Kinase Substrate), in Salmonella infections. We hypothesize that MARCKS protein function is essential for Salmonella-induced neutrophil recruitment and activation, epithelial invasion, and the overall survival of Salmonella in the host intestine. We will use a MARCKS peptide inhibitor to investigate the role of MARCKS in neutrophil antimicrobial responses in vitro and during calf infection. We will establish the role of MARCKS in Salmonella intestinal invasion in vitro and tissue colonization during calf infection. Finally, we will establish the role of our MARCKS peptide inhibitor on antimicrobial resistance development during calf infection. These experiments will (1) establish the basic biology of MARCKS protein during infection and (2) establish the efficacy of a MARCKS peptide inhibitor as a host-directed therapeutic alternative to treat bovine salmonellosis. Salmonella infections are a threat to both human and bovine health so alternatives to traditional antimicrobials are critically needed to combat this important pathogen. The proposed studies will directly inform development of a non-antimicrobial therapeutic to prevent and treat Salmonella in cattle.

Date: 02/01/17 - 11/01/20
Amount: $126,358.00
Funding Agencies: Morris Animal Foundation

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.


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