Dept. of Pharmacology, Kansas State University
PhD, Cornell University, 1991
Research efforts are focused on understanding the physiological regulation of epithelial ion transport and barrier functions. Transepithelial movement of ions provides for electrolyte and fluid homeostasis and, in the case of milk, is necessary for production. Dysfunction of epithelial transport mechanisms, especially the anion channel CFTR, is associated with reproductive, pancreatic, renal, intestinal, and pulmonary disorders. In the laboratory, we strive to achieve a better understanding of epithelial physiology and to develop interventions that prevent or overcome such pathological conditions.
Common mechanisms to accomplish ion transport are employed by a variety of epithelia. However, the cellular and subcellular location, along with regulatory apparatus, provides for unique combinations of mechanisms to support specific needs at each locale. Furthermore, a particular epithelium can modify its function depending upon the stage of tissue development or the endocrine state of the individual. In the laboratory, we are studying reproductive, renal, intestinal and mammary epithelia in order to understand their unique transport capabilities. These observations are particularly instructive for reproductive and mammary epithelia since relatively little is known regarding the mechanisms that they employ.
We developed an in vitro system to study ion transport by epithelia lining the male reproductive tract. This system allows us to identify mechanisms of ion transport in this tissue along with the hormones and neurotransmitters that modulate such activity. This line of investigation is particularly important as we try to understand the causes of congenital bilateral absence of the vas deferens (CBAVD), a form of infertility that commonly affects cystic fibrosis patients. CBAVD has recently gained recognition as a 'mild' form of cystic fibrosis.
The laboratory collaborates with Dr. John Tomich (Department of Biochemistry) in a project to develop synthetic channel forming peptides for the treatment of cystic fibrosis. Since the primary defect in cystic fibrosis is the loss of an epithelial anion channel, we reasoned that providing such a conductance could reduce or preclude the effects of the disease.
The production of milk defines mammals. Major components of milk include proteins, fats, carbohydrates, and minerals. These components are present in varying proportions, depending upon species. A major focus in the laboratory is to determine the mechanisms that can account for the concentrations of monovalent ions with a primary focus on Na+. Human milk has the lowest Na+ concentration of virtually all species. Thus, human mammary epithelial cell systems are the primary model for this line of investigation. Mastitis is an environmentally induced loss of epithelial integrity that affects a significant proportion of the human population, but has greatest impact on the dairy industry. An in vitro bovine mammary cell system is being employed in the laboratory to identify factors that lead from environmental insult to the loss of epithelial function. Finally, there is an ongoing collaboration with Dr. Ronette Gehring that focuses on the transport of xenobiotic compounds (environmental toxins, pharmaceuticals, etc.) across the mammary epithelium. This line of investigation seeks to identify mechanisms that can account for the active movement of these solutes into or from milk.
We gratefully acknowledge ongoing or past support from the National Institutes of Health, the United States Department of Agriculture, and the Cystic Fibrosis Foundation.'
Lillich JD, Ray-Miller W, Silver K, Davis EG, and Schultz BD. (2011) Intra-abdominal hyaluronan concentration in peritoneal fluid of horses with sudden signs of severe abdominal pain. Am J Vet Res 72(12):1666-73.
Schultz BD. (2010) Proteomics reveal the breadth and limits of model systems inferences. Focus on "proteomic analysis of V-ATPase-rich cells harvested from the kidney and epididymis by fluorescence-activated cell sorting". Am J Physiol 298: C1303-1304.
Pierucci-Alves F, Duncan CL, Lillich JD, and Schultz BD. (2010) Porcine vas deferens luminal pH is acutely increased by systemic xylazine administration. Biol Reprod 82: 132-135.
Al-Bataineh MM, van der Merwe D, Schultz BD, and Gehring R. (2010) Tumor necrosis factor alpha increases P-glycoprotein expression in a BME-UV in vitro model of mammary epithelial cells. Biopharmaceutics & Drug Disposition 31: 506-515.
Pierucci-Alves F, Duncan CL, and Schultz BD. (2009) Testosterone upregulates anion secretion across porcine vas deferens epithelia in vitro. Biol Reprod 81: 628-635.
Martin J, Malreddy P, Iwamoto T, Freeman LC, Davidson HJ, Tomich JM, and Schultz BD. (2009) NC-1059, a channel-forming peptide modulates drug delivery across in vitro corneal epithelium. Invest Ophthalmol Vis Sci 50: 3337-3345.
Al-Bataineh MM, van der Merwe D, Schultz BD, and Gehring R. (2009) Cultured mammary epithelial monolayers (BME-UV) express functional organic anion and cation transporters. J Vet Pharmacol Ther 32: 422-428.
Schultz BD. Purinergic agonists flex vas deferens muscle. (2008) J Physiol 586: 5287.
Pierucci-Alves F and Schultz BD. (2008) Bradykinin-stimulated cyclooxygenase activity stimulates human and porcine vas deferens epithelial anion secretion in vitro. Biol Reprod 79: 501-509.
Somasekharan S, Brandt R, Iwamoto T, Tomich JM, and Schultz BD. (2008) Epithelial barrier modulation by a channel forming peptide. J Memb Biol 222: 17-30.
Bruce Schultz, PhD