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Associate Professor
114 McCord Hall
2640 Morgan Circle
Knoxville, TN 37996-4588
(865) 974-7225
Fax: (865) 974-9043
Email: pighetti@utk.edu
Research Appointment: 75%
Teaching Appointment: 25%
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EDUCATION and TRAINING
PhD in Pathobiology, The Pennsylvania State University
MS in Pathobiology, The Pennsylvania State University
BS in Dairy Production, Minor in Business, The Pennsylvania State
University
RESEARCH INTERESTS
My long-term research goals seek to improve animal health and subsequent food safety by elucidating genetic-based mechanisms that contribute to disease susceptibility. Once these mechanisms are identified, improved preventive and therapeutic strategies can be developed to counteract ‘weak-links’ in an animals defense system. Most of my research centers on mastitis, an inflammation of the mammary gland commonly caused by bacteria. In the United States alone, the costs associated with this disease are estimated at $2 billion a year! Mastitis not only impacts animal health and productivity, but also impairs milk safety by increasing the potential for transfer of foodborne pathogens and antibiotic resistance. Therefore, identifying means of reducing the incidence and severity of mastitis are critical for improving dairy cow health and milk quality.
 Discovery of Genetic Markers for Mastitis Susceptibility and Resistance in Dairy Cattle. Current methods of selecting for cattle more resistant to mastitis are relatively slow and limit the ability to build cattle populations more resistant to disease. Therefore, identification of specific genetic markers indicative of mastitis would increase the speed and accuracy of the selection process, ultimately leading to a healthier cattle population. To accomplish this, my group has searched for the presence of single nucleotide polymorphisms (SNP) in the DNA of immune-related genes. Once the SNP are identified, the association with clinical and subclinical mastitis is evaluated using an extensive database previously developed by Dr. Oliver. Thus far, my group has identified a series of polymorphisms in two immune genes, CXCR1 and NRAMP1, associated with subclinical and clinical mastitis.
 Identify Mechanisms Associated with Impaired Immunity in Dairy Cows Genetically More Susceptible to Mastitis. Although management-based strategies have been developed that minimize the incidence of mastitis, this disease continues to be a significant problem to the industry. Novel preventive and therapeutic strategies that directly impact a cows’ ability to withstand or reduce the severity of disease are needed. With identification of several genetic markers associated with mastitis in dairy cows, we are in a unique position to begin understanding the mechanisms that contribute to mastitis susceptibility. We have determined that cattle genetically more susceptible to mastitis also have significantly impaired migration of neutrophils, a type of white blood cell. Because the speed at which neutrophils reach the site of infection often determines whether an infection is cleared or not, this effect may directly contribute to the observed increase in mastitis. Furthermore, the ability of these cells to produce reactive oxygen species and survive also was altered and may further influence mastitis occurrence. Subsequent studies have revealed that impaired neutrophil function is partly associated with a reduced ability of interleukin-8 to bind its receptor, CXCR1 – the gene in which the marker identified by my group is located. This finding may have direct implications in the efficacy of interleukin-8 agonists and antagonists currently being designed to ameliorate the effects of interleukin-8 in inflammatory diseases such as bovine respiratory disease. Additional studies indicate that impaired neutrophil function also is partly mediated by a downstream signaling event common to several different stimuli, suggesting the genetic marker in CXCR1 also may be tied to a genetic defect in another gene. Using a combination of genomic and proteomic approaches, we are in the process of identifying critical signaling events and proteins needed for neutrophil function. Discovery of these key events and proteins will provide additional insight into the development of pro- and anti-inflammatory therapies that target neutrophils. Moreover, because neutrophil activity is relatively consistent across species, any developed therapies also may prove effective in other species – including humans.
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