Professor and Interim Department Head
PhD, Pharmacology, 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.
Schultz BD. 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, 2010.
Pierucci-Alves F, Duncan CL, Lillich JD, and Schultz BD. Porcine vas deferens luminal pH is acutely increased by systemic xylazine administration. Biol Reprod 82: 132-135, 2010.
Al-Bataineh MM, van der Merwe D, Schultz BD, and Gehring R. 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, 2010.
Lillich JD, Ray-Miller W, Silver K, Davis EG, and Schultz BD. Identification of intra-abdominal hyaluronan in peritoneal fluid of equine patients presenting with an acute abdomen. Am J Vet Res Accepted for publication (04 October, 2010), 2010.
Pierucci-Alves F, Duncan CL, and Schultz BD. Testosterone upregulates anion secretion across porcine vas deferens epithelia in vitro. Biol Reprod 81: 628-635, 2009.
Martin J, Malreddy P, Iwamoto T, Freeman LC, Davidson HJ, Tomich JM, and Schultz BD. NC-1059, a channel-forming peptide modulates drug delivery across in vitro corneal epithelium. Invest Ophthalmol Vis Sci 50: 3337-3345, 2009.
Al-Bataineh MM, van der Merwe D, Schultz BD, and Gehring R. Cultured mammary epithelial monolayers (BME-UV) express functional organic anion and cation transporters. J Vet Pharmacol Ther 32: 422-428, 2009.
Schultz BD. Purinergic agonists flex vas deferens muscle. J Physiol 586: 5287, 2008.
Pierucci-Alves F and Schultz BD. Bradykinin-stimulated cyclooxygenase activity stimulates human and porcine vas deferens epithelial anion secretion in vitro. Biol Reprod 79: 501-509, 2008.
Somasekharan S, Brandt R, Iwamoto T, Tomich JM, and Schultz BD. Epithelial barrier modulation by a channel forming peptide. J Memb Biol 222: 17-30, 2008.
van Ginkel FW, Iwamoto T, Schultz BD, and Tomich JM. Immunity to a self-derived, channel-forming peptide in the respiratory tract. Clin Vaccine Immunol 15: 260-266, 2008.
Veilleux S, Holt N, Schultz BD, and Dubreuil JD. Escherichia coli EAST1 toxin toxicity of variants 17-2 and O 42. Comp Immunol Microbiol Infect Dis 31: 567-578, 2008.
Hagedorn TM, Carlin RW, and Schultz BD. Oxytocin and vasopressin stimulate anion secretion by human and porcine vas deferens epithelia. Biol Reprod 77: 416-424, 2007.
Quesnell RR, Han X, and Schultz BD. Glucocorticoids stimulate ENaC upregulation in bovine mammary epithelium. Am J Physiol 292: C1739-1745, 2007.
Quesnell RR, Erickson JE, Schultz BD. Apical electrolyte concentration modulates barrier function and tight junction protein localization in bovine mammary epithelium. Am J Physiol Cell Physiol 292: C305-318, 2007.
Sabah JR, Schultz BD, Brown ZW, Nguyen AT, Reddan J, and Takemoto LJ. Transcytotic passage of albumin through lens epithelial cells. Invest Ophthalmol Vis Sci 48: 1237-1244, 2007.
Nakaya K, Harbidge DG, Wangemann P, Schultz BD, Green E, Wall SM, and Marcus DC. Lack of pendrin HCO3- transport elevates vestibular endolymphatic [Ca2+] by inhibition of acid-sensitive TRPV5 and TRPV6 channels. Am J Physiol 292: F1314-1321, 2007.
Carlin RW, Sedlacek RL, Quesnell RR, Pierucci-Alves F, Grieger DM, Schultz BD. PVD9902, a porcine vas deferens epithelial cell line that exhibits neurotransmitter-stimulated anion secretion and expresses numerous HCO3(-) transporters. Am J Physiol Cell Physiol 290: C1560-1571, 2006.
Carlin RW, Davis D, Weiss M, Schultz BD, Troyer D. Expression of early transcription factors Oct4, Sox2 and Nanog by porcine umbilical cord (PUC) matrix cells. Reprod Biol Endocrinol 4: 8, 2006.
Shank LP, Broughman JR, Takeguchi W, Cook GA, Robbins A, Hahn L, Radke G, Iwamoto T, Schultz BD, Tomich JM. Redesigning channel-forming peptides: Amino acid substitutions that enhance rates of supermolecular self-assembly and raise ion transport activity. Biophys J 90: 2138-2150, 2006.
Singh AK, Schultz BD, van Driessche W, Bridges RJ. Transepithelial fluctuation analysis of chloride secretion. J Cyst Fibros 3 Suppl 2: 127-132, 2004.
Moeser AJ, Haskell MM, Shifflett DE, Little D, Schultz BD, Blikslager AT. ClC-2 chloride secretion mediates prostaglandin-induced recovery of barrier function in ischemia-injured porcine ileum. Gastroenterology 127: 802-815, 2004.
Broughman JR, Brandt RM, Hastings C, Iwamoto T, Tomich JM, Schultz BD. Channel-forming peptide modulates transepithelial electrical conductance and solute permeability. Am J Physiol Cell Physiol 286: C1312-1323, 2004.
Cook GA, Prakash O, Zhang K, Shank LP, Takeguchi WA, Robbins A, Gong YX, Iwamoto T, Schultz BD, Tomich JM. Activity and structural comparisons of solution associating and monomeric channel-forming peptides derived from the glycine receptor m2 segment. Biophys J 86: 1424-1435, 2004.
Carlin RW, Lee JH, Marcus DC, Schultz BD. Adenosine stimulates anion secretion across cultured and native adult human vas deferens epithelia. Biol Reprod 68: 1027-1034, 2003.
Singh AK, Schultz BD, van Driessche W, Bridges RJ. Transepithelial fluctuation analysis of chloride secretion. In: Sheppard DN (ed.) European Working Group on CFTR Expression: Virtual Repository: Cell Physiology: Instituto Nacional de Saúde Dr. Ricardo Jorge, Portugal.; 2003.
Phillips ML, Schultz BD. Steroids modulate transepithelial resistance and Na+ absorption across cultured porcine vas deferens epithelia. Biol Reprod 66: 1016-1023, 2002.
Carlin RW, Quesnell RR, Zheng L, Mitchell KE, Schultz BD. Functional and molecular evidence for Na+-HCO3- cotransporter in porcine vas deferens epithelia. Am J Physiol Cell Physiol 283: C1033-1044, 2002.
Broughman JR, Shank LP, Prakash O, Schultz BD, Iwamoto I, Tomich JM, Mitchell KE. Structural Implications of Placing Cationic Residues at either the NH2- or COOH-Terminus in a Pore-forming Synthetic Peptide. J Membr Biol 190: 93-103, 2002.
Broughman JR, Shank LP, Takeguchi W, Schultz BD, Iwamoto T, Mitchell KE, Tomich JM. Distinct structural elements that direct solution aggregation and membrane assembly in the channel-forming peptide M2GlyR. Biochemistry 41: 7350-7358, 2002.
Sedlacek RL, Carlin RW, Singh AK, Schultz BD. Neurotransmitter-stimulated ion transport by cultured porcine vas deferens epithelium. Am J Physiol Renal Physiol 281: F557-570, 2001.
Schmidt CR, Carlin RW, Sargeant JM, Schultz BD. Neurotransmitter-stimulated ion transport across cultured bovine mammary epithelial cell monolayers. J Dairy Sci 84: 2622-2631, 2001.
Broughman JR, Mitchell KE, Sedlacek RL, Iwamoto T, Tomich JM, Schultz BD. NH(2)-terminal modification of a channel-forming peptide increases capacity for epithelial anion secretion. Am J Physiol Cell Physiol 280: C451-458, 2001.
O'Donnell EK, Sedlacek RL, Singh AK, Schultz BD. Inhibition of enterotoxin-induced porcine colonic secretion by diarylsulfonylureas in vitro. Am J Physiol Gastrointest Liver Physiol 279: G1104-1112, 2000.
Singh AK, Schultz BD, Katzenellenbogen JA, Price EM, Bridges RJ, Bradbury NA. Estrogen inhibition of cystic fibrosis transmembrane conductance regulator-mediated chloride secretion. J Pharmacol Exp Ther 295: 195-204, 2000.