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Research Interests:
Research efforts are focused on understanding the
physiological regulation of epithelial ion transport. 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 pancreatic, renal, intestinal, reproductive, 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 have recently 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.
Mastitis is an environmentally induced loss of
epithelial integrity that 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. We are also developing treatment
regimen that will accelerate recovery to full production.
We gratefully acknowledge ongoing support from the
National Institutes of Health, the United States Department of Agriculture, and the Cystic
Fibrosis Foundation.
Selected publications:
Pierucci-Alves F and Schultz BD.
Bradykinin-stimulated cyclooxygenase activity stimulates vas deferens
epithelial anion secretion in vitro. Biol Reprod under review, 2008.
Somasekharan S, Brandt R, Iwamoto T, Tomich JM, and
Schultz BD. Epithelial
barrier modulation by a channel forming peptide. J Memb Biol being
revised, 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 Accepted for publication,
2007.
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 2007; 292: C305-318.
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.
Veilleux S, Holt N, Schultz BD,
and Dubreuil JD. Toxicity of variants 17-2 and O 42 of Escherichia coli
EAST1 toxin. Comparative Immunology, Microbiology & Infectious Diseases:
Accepted for publication, 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 2006; 290: C1560-1571.
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
2006; 4: 8.
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 2006; 90: 2138-2150.
Singh AK, Schultz BD,
van Driessche W, Bridges RJ. Transepithelial fluctuation analysis of
chloride secretion. J Cyst Fibros 2004; 3 Suppl 2: 127-132.
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
2004; 127: 802-815.
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 2004; 286:
C1312-1323.
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 2004; 86: 1424-1435.
Carlin RW, Lee JH, Marcus DC, Schultz BD.
Adenosine stimulates anion secretion across cultured and native adult
human vas deferens epithelia. Biol Reprod 2003; 68: 1027-1034.
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 2002; 66:
1016-1023.
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 2002; 283: C1033-1044.
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 2002;
190: 93-103.
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
2002; 41: 7350-7358.
Sedlacek RL, Carlin RW, Singh AK, Schultz
BD. Neurotransmitter-stimulated ion transport
by cultured porcine vas deferens epithelium. Am J Physiol Renal Physiol
2001; 281: F557-570.
Schmidt CR, Carlin RW, Sargeant JM,
Schultz BD. Neurotransmitter-stimulated ion
transport across cultured bovine mammary epithelila cell monolayers. J
Dairy Sci 2001; 84: 2622-2631.
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 2001;
280: C451-458.
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 2000; 279: G1104-1112.
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 2000; 295:
195-204.
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