JavaScript is currently not supported or is disabled by this browser. Please enable JavaScript for full functionality.
PROFESSIONAL ACTIVITIES AND SERVICES
1970-1974 University of California, San Diego; B.A. Biology, magna cum laude
1974-1980 University of California, Los Angeles; Ph.D. Molecular Biology
1980-1983 University of California, Riverside; Postgraduate Research Biochemist
1983-1984 University of California, San Diego; Postdoctoral Fellow, Cell Biology
1985, Winter Quarter Visiting Assistant Professor for introductory endocrinology course, Department of Biology, UCLA.
1984-1993 Assistant Research Professor, Department of Biochemistry, UCR
1994-1995 Associate Research Professor, Department of Biochemistry, UCR
1987-1991 Fall Quarter Lecturer for introductory biochemistry course (with lab), Department of Biochemistry, UCR.
1994-2001 Associate Graduate Faculty (adjunct), Marshall University, WV
1995-2000 Assistant Professor, Department of Nutrition and Food Sciences and the Biotechnology Center, Utah State University (courses: Introductory Nutrition, Advanced Nutrition, Endocrine Aspects of Nutrition, graduate seminar).
2001-2005 Associate Professor, Department of Nutrition and Food Sciences and the Biotechnology Center, Utah State University
2002-2003 Program Director for Nutrition Science
2005-present Professor, Department of Nutrition and Food Sciences and The Center for Integrated BioSystems
2005-present Program Director for Nutrition Science
American Association for the Advancement of Science
Sigma Xi
Endocrine Society
American Society for Bone and Mineral Research
American Society for Cell Biology
American Society for Biochemistry and Molecular Biology
American Society for Nutrition
Representative Publications
Nemere, I (1999) 24,25-dihydroxyvitamin D3 suppresses the rapid actions of 1,25-dihydroxyvitamin D3 and parathyroid hormone in chick intestine. J. Bone Mineral Res 14:1543-1549.
Nemere, I., Ray, R., McManus, W. (2000) Immunochemical studies on the putative plasmalemmal receptor for 1,25-dihydroxyvitamin D3: I. chick intestine. Am J Physiol. 278: E1104-E1114.
Larsson, B. and Nemere, I. (2003) Effect of growth and maturation on membrane-initiated actions of 1,25-dihydroxyvitamin D3. I. Calcium transport, receptor kinetics, and signal transduction in intestine of male chickens. Endocrinology 144: 1726-1735.
Nemere, I., Farach-Carson, M.C., Rohe, B., Sterling, T., Norman, A.W., Boyan, B.D., and Safford S., (2004). Ribozyme knockdown functionally links a 1,25(OH)2D3 membrane binding protein (1,25D3-MARRS bp) and phosphate uptake in intestinal cells. Proc Natl Acad Sci USA 101: 7392-7397.
Sterling, T.M. and Nemere, I. (2005) 1,25-Dihydroxyvitamin D3 Stimulates Vesicular Transport within 5 sec in Polarized Intestinal Epithelial Cells. J. Endocrinol. 185: 81-91.
Nemere, I. (2005) The 1,25D3-MARRS protein: Contribution to steroid-stimulated uptake in chicks and rats. Steroids 70: 455-457.
Khanal, R., and Nemere I. (2007) Membrane receptors for vitamin D metabolites Critical Reviews in Eukaryotic Gene Expression 17: 31-47.
Peery S and Nemere I (2007) Contributions of pro-oxidant and anti-oxidant conditions to the actions of 24,25-dihydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 on phosphate uptake in intestinal cells. J Cellular Biochem 101: 1176-1184.
Research Interests
Broadly defined, our research interests are in the area of hormone-mediated ion transport across membranes, vesicular flow and the role of cytoskeletal elements in cellular responses. As a specific model system we are studying intestinal calcium and phosphate transport stimulated by the seco-steroid hormone 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and the peptide hormone PTH. As a graduate student, I developed the concepts of non-genomic mechanisms of actions for steroid hormones in rat intestinal epithelium, as well as calcium transport by means of a vesicular pathway. I have subsequently continued to study these postulates in the chick.
Past projects have included a vascular perfusion system using the duodenal loop of normal (chronically vitamin D replete) chicks, in which 1,25(OH)2D3 rapidly stimulates calcium or phosphate transport (within 2 min), by a mechanism that is membrane receptor-mediated but independent of genome activation. Collaborative studies have indicated that signal transduction mechanisms for augmenting calcium transport include Ca2+-channel activation in the basal lateral membrane, and stimulation of protein kinases. This model system also indicates that the genomic actions of 1,25(OH)2D3, most notably to induce the expression of the calcium binding protein calbindin-D28K (CaBP), and the stimulation of calcium transport occur by separate pathways but are ultimately complementary. For this reason, an analysis of the intracellular components of transport has been undertaken.
Biochemical studies with vitamin D-deficient chicks dosed for different times with 1,25(OH)2D3 have indicated that during transport, 45Ca is first associated with endocytic vesicles, and later with lysosomes. The time course of organellar loading after 1,25(OH)2D3 administration is in good agreement with the time course of net transport as judged by 45Ca in serum. Dose-response studies also support a vesicular transport pathway. Light- and electron-microscopic studies have indicated that CaBP is concentrated in membrane-delimited vesicles rather than in cytoplasm as once believed.
The overall view of transport that has emerged from these studies is that calcium is taken up at the brush border membrane into endocytic vesicles, the contents transferred to lysosomes, with the exocytosis of lysosomal 45Ca at the basal lateral membrane completing the transport process. In normal chicks, binding of the seco-steroid hormone 1,25(OH)2D3 to a putative basal lateral membrane receptor results in the activation of a Ca2+-channel, which in turn induces this modified form of stimulus secretion coupling.
Since there is evidence that the calcium-bearing organelles move along microtubules (transport is inhibited by colchicine), tubulin has also been the subject of investigation. Vitamin D-status has been found to affect the expression of α-tubulin mRNA, and the amount of [3H]-colchicine-binding tubulin subunits. The effect of vitamin D status on microtubule isotype expression was studied by isoelectric focusing, immunoblotting, and Western analyses, and a protein corresponding to α-tubulin found to be influenced hormone treatment.
Using solubilized membrane proteins, traditional binding studies were undertaken including saturation analyses, estimations of KD, and competitions between 1,25(OH)2D3 and various other vitamin D metabolites and analogs. Purification of the 1,25(OH)2D3 membrane associated, rapid response steroid binding (1,25D3-MARRS) protein resulted in the identification, purification, and N-terminal microsequencing of a 65 kD protein. Polyclonal antisera, raised to a synthetic peptide corresponding to the sequence, reacted with a single protein band on Western analysis; a protein of equivalent molecular weight was labeled with the affinity ligand [14C] 1,25(OH)2D3 –bromoacetate. Microscopic studies revealed that although the receptor is largely confined to the basal lateral membrane, ligand binding induces relocalization to the nucleus. Western analyses with antibody to the classical nuclear receptor, indicated that the two proteins behave as separate entities. However, antisera to the membrane receptor inhibited not only hormone-induced signal transduction events such as activation of PK C and phosphate uptake in isolated intestinal cells, but also steroid-regulated growth phenomena in rat chondrocytes. We have recently found that ‘turbo-charging’ transport through the 1,25D3-MARRS receptor system is very important during growth and diminishes with adulthood. We plan to test this observation, and what may be fundamental signaling changes, in rats and mice to expand biomedical relevance.
We have identified and sequenced the cDNA for the membrane receptor from a chicken library. The in vitro translation product specifically bound hormone and reacted with highly specific antisera on Western analyses. Efforts are currently underway to over express the protein in prokaryotic, as well as mammalian cells, for further characterization of binding activity and post translational modification sites. A ribozyme directed against the 1,25D3-MARRS receptor mRNA exhibited cleavage activity in vitro, and transfection into cultured intestinal cells abolishes hormone-stimulated phosphate uptake, and PKC activation, and severely reduces specific binding to membrane fractions (but not the nuclear receptor) and protein levels, as judged by Western analyses.
Another metabolite of vitamin D, 24,25(OH)2D3, is currently being studied because of its ability to inhibit the membrane-initiated effects of 1,25(OH)2D3 on calcium and phosphate transport. A putative receptor protein for this metabolite has been purified, and identified as the enzyme catalase. We have found that the mechanism of 24,25(OH)2D3-mediated inhibition can be attributed to an inhibition of catalase specific activity with concomitant increases in hydrogen peroxide. This reactive oxygen species interferes with 1,25D3-MARRS receptor function by oxidizing thiols that are required for binding 1,25(OH)2D3.
. Nemere, I. (1996) Apparent non-nuclear regulation of intestinal phosphate transport: Effects of 1,25-dihydroxyvitamin D3, 24,25-dihydroxyvitamin D3, and 25-hydroxyvitamin D3. Endocrinology 137: 2254-2261.
57. Nemere, I (1996) Parathyroid hormone rapidly stimulates phosphate transport in perfused duodena: Lack of modulation by vitamin D metabolites. Endocrinology 137: 3750-3755.
58. Nemere, I. (1996) Genomic and nongenomic actions of vitamin D on calcium transport in intestine. Poultry and Avian Biology Reviews 7: 205-216.
59. Nemere, I., Ray, R. and Jia, Z. (1997) Further characterization of the basal lateral membrane receptor for 1,25(OH)2D3 in chick intestine. In, Vitamin D: Chemistry, Biology and Clinical Applications of the Steroid Hormone; A.W. Norman, R. Bouillon, and M. Thomasset (eds.), University of California, Riverside, pp 387-388
60. Nemere, I. and Farach-Carson, M.C. (1998) Membrane receptors for steroid hormones: A case for specific cell surface binding sites for vitamin D metabolites and estrogens. Biochem. Biophys. Res. Commun. 248: 443-449.
61. Nemere, I., Schwartz, Z., Pedrozo, H., Sylvia, V.L., Dean, D.D., and Boyan, B.D. (1998) Identification of a membrane receptor for 1,25-dihydroxy vitamin D3 which mediates rapid activation of protein kinase C. J Bone Mineral Res. 13: 1353-1359.
62. Boyan, B.D., Sylvia, V.L., Dean, D.D., Pedrozo, H., Del Toro, F., Nemere, I., Posner, G.H., and Schwartz, Z. (1999) 1,25-(OH)2D3 modulates growth plate chondrocytes via membrane receptor-mediated protein kinase C by a mechanism that involves changes in phospholipid metabolism and the action of arachadonic acid and PGE2. Steroids 64: 129-136.
63. Pedrozo, H.A., Schwartz, Z., Rimes, S., Sylvia, V.L., Nemere, I., Posner, G., Dean, D.D., and Boyan, B.D. (1999) Physiological importance of the 1,25-(OH)2D3 membrane receptor and evidence for a membrane receptor specific for 24,25-(OH)2D3. J. Bone Mineral Res 14: 856-867.
64. Nemere, I (1999) 24,25-dihydroxyvitamin D3 suppresses the rapid actions of 1,25-dihydroxyvitamin D3 and parathyroid hormone in chick intestine. J. Bone Mineral Res 14:1543-1549.
65. Jia, Z. and Nemere, I. (1999) Immunochemical studies on the putative plasmalemmal receptor for 1,25-dihydroxyvitamin D3: II. chick kidney and brain. Steroids 64: 541-550.
66. Nemere, I., Ray, R., McManus, W. (2000) Immunochemical studies on the putative plasmalemmal receptor for 1,25-dihydroxyvitamin D3: I. chick intestine. Am J Physiol. 278: E1104-E1114.
67. Nemere, I., and Campbell, K. (2000) Immunochemical studies on the plasmalemmal membrane receptor for 1,25-dihydroxyvitamin D3: Effect of vitamin D status. Steroids 65: 451-457.
68. Nemere, I., Larsson, D., Sundell, K. (2000) Presence of a specific binding moiety for 1,25-dihydroxyvitamin D3 in basal lateral membranes of enterocytes from the freshwater carp. Am. J. Physiol. 297:E614-621.
69. Mesbah, M., Papagerakis, P., Teillaud, C., Nemere, I., and Berdal, A. (2000) Immunolocalization of membrane vitamin D receptor in human tooth germ. In, Vitamin D Endocrine System. Structural, Biological, Genetic, and Clinical Aspects (A.W. Norman, R. Bouillon, M. Thomasset, eds.) University of California, Riverside, pp. 707-710.
70. Teillaud, C., Nemere, I., MacDougall, M., Mesbah, M., Forest, N., and Berdal, A. (2000) Expression of 1α,25-(OH)2D3 membrane receptor in murine dental cells. In, Vitamin D Endocrine System. Structural, Biological, Genetic, and Clinical Aspects (A.W. Norman, R. Bouillon, M. Thomasset, eds.) University of California, Riverside, pp. 711-714.
71. Nemere, I. (2000) Membrane-initiated effects of 1,25(OH)2D3: modulation by vitamin D status and 24,25(OH)2D3. In, Vitamin D Endocrine System. Structural, Biological, Genetic, and Clinical Aspects (A.W. Norman, R. Bouillon, M. Thomasset, eds.) University of California, Riverside, pp. 727-730.
72. Pietras, R.J., Nemere, I., and Szego, C. M. (2001) Cell membrane forms of steroid hormone receptors. Endocrine 14:417-427.
73. Larsson, D., Nemere, I., Sundell, K (2001) Putative basal lateral membrane receptors for 24,25-dihydroxyvitamin D3 in carp and Atlantic cod enterocytes: characterization of binding and 24R,25-dihydroxyvitamin D3 and 24S,25-dihydroxyvitamin D3 dependent effects on intracellular calcium regulation. J Cellular Biochem 83: 171-186.
74. Larsson, D. and Nemere, I. (2001) 24,25-Dihydroxyvitamin D3 and intestinal calcium transport: From receptors to physiological response. Recent Research Developments in Endocrinology Vol. 2 (part 1): 183-198.
75. Nemere, I., Yazzie-Atkinson, D. Johns, D, and Larsson, D. (2002) Biochemical characterization and purification of a binding protein for 24,25-dihydroxyvitamin D3 from chick intestine. J Endocrinol 172: 211-219
76. Schwartz, Z., Sylvia, V.L., Larsson, D., Nemere, I., Casasola, D., Dean, D.D., and Boyan, B.D. (2002) 1α,25-(OH)2D3 Regulates chondrocyte matrix vesicle protein kinase C directly via G-protein dependent mechanisms and indirectly via incorporation of PKC during matrix vesicle biogenesis. J. Biol Chem. 277:11828-11837.
77. Boyan, B.D., Bonewald, L, Sylvia, V. Nemere, I., Larsson, D., Norman, A.W., Rosser, Dean, D.D, and Schwartz, Z (2002) Evidence for distinct membrane receptors for 1α,25-dihydroxyvitamin D3 and 24R,25-dihydroxyvitamin D3 in osteoblasts. Steroids 67: 235-246.
78. Nemere, I. and Larsson, D (2002) Does PTH have a direct effect on intestine? J. Cell. Biochem. 86:29-34.
79. Zhao, B. and Nemere, I. (2002) 1,25(OH)2D3-Mediated phosphate uptake in isolated chick intestinal cells: effect of 24,25(OH)2, signal transduction activators, and age. J. Cell. Biochem. 86:497-508.
80. Mesbah, M., Nemere, I., Papagerakis, P., Nefussi, J-R, Orestes-Cardoso, S., Nessmann, C., Berdal, A. (2002) Expression of a 1,25-dihydroxyvitamin D3 membrane-associated rapid-response steroid binding protein during human tooth and bone development and biomineralization. J. Bone Mineral Res. 17: 1588-1596.
81. Larsson, D. and Nemere, I. (2002) Vectorial transcellular calcium transport in intestine: Integration of current models. J. Biomedicine Biotechnology 2(3): 117-119.
82. Larsson, D., Sundell, K., Larsson, B., and Nemere, I. (2002) Enterocyte calcium uptake and extrustion: transport mechanisms and endocrine regulation. Recent Research Developments in Membrane Biology 1: 61-74.
83. Farach-Carson, M.C., and Nemere, I (2003) Membrane receptors for vitamin D steroid hormones: Potential new drug targets. Current Drug Targets 4: 67-76.
84. Nemere, I., Pietras, R.J., and Blackmore, P.F. (2003) Membrane receptors for steroid hormones: Signal transduction and physiological significance. J. Cellular Biochem. 88: 438-445.
85. Larsson, D., Nemere, I., Aksnes, L., and Sundell, K (2003) Environmental salinity regulates receptor expression, cellular effects and circulating levels of two antagonizing hormones in rainbow trout. Endocrinology 144: 559-566.
86. Larsson, B. and Nemere, I. (2003) Effect of growth and maturation on membrane-initiated actions of 1,25-dihydroxyvitamin D3. I. Calcium transport, receptor kinetics, and signal transduction in intestine of male chickens. Endocrinology 144: 1726-1735.
87. Szego, C.M., Pietras, R.J. and Nemere, I. (2003) Plasmalemmal receptors for steroid hormones. In, Encyclopedia of Hormones, Vol II., pgs 657-671, (Henry, H.L. and Norman, A.W., eds.), Academic Press CA.
88. Berdal, A., Mesbah, M., Papagerakis, P., and Nemere, I. (2003) Putative membrane receptor for 1,25(OH)2 vitamin D3 in human mineralized tissues during prenatal development. Connect Tissue Res. 44 (Suppl 1): 136-140.
89. Phadnis, R. and Nemere, I. (2003) Direct, Rapid effect of 25-hydroxyvitamin D3 on isolated intestinal cells. J. Cellular Biochem. 90: 287-293.
90. Larsson, B. and Nemere, I. (2003) Effect of growth and maturation on membrane-initiated actions of 1,25-dihydroxyvitamin D3. II. Calcium transport, receptor kinetics, and signal transduction in intestine of female chickens. J. Cellular Biochem. 90: 901-913.
91. Nemere, I., Farach-Carson, M.C., Rohe, B., Sterling, T., Norman, A.W., Boyan, B.D., and Safford S., (2004). Ribozyme knockdown functionally links a 1,25(OH)2D3 membrane binding protein (1,25D3-MARRS bp) and phosphate uptake in intestinal cells. Proc Natl Acad Sci USA 101: 7392-7397.
92. Nemere, I., Safford, S.E., Rohe, B., DeSouza, M.M., and Farach-Carson, M.C. (2004) Identification and characterization of 1,25D3 Membrane-Associated Rapid Response, Steroid (1,25D3-MARRS) binding protein. J. Steroid Biochem and Mol Biol 89-90:281-285
93. Nemere, I. (2004) Physiological role of a 1,25(OH)2D3 membrane receptor. Recent Research Developments in Endocrinology 4: 73-83.
94. Walters, M.R. and Nemere, I. (2004) Steroid hormone receptors: Membrane-associated and nuclear forms. Cellular Molecular Life Sciences 61: 2309-2321
95. Teillaud, C., Nemere, I., Boukhobza, F., Mathiot, C., Conan, N., Oboeuf, M., Hotton, D., MacDougall, M., and Berdal, A. (2005) Modulation of 1α,25-dihydroxyvitamin D3-membrane associated, rapid response steroid binding protein expression in mouse odontoblasts by 1α,25-(OH)2D3 J. Cellular Biochem. 94: 139-152.
96. Sterling, T.M. and Nemere, I. (2005) 1,25-Dihydroxyvitamin D3 Stimulates Vesicular Transport within 5 sec in Polarized Intestinal Epithelial Cells. J. Endocrinol. 185: 81-91.
97. Nemere, I. (2005) The 1,25D3-MARRS protein: Contribution to steroid-stimulated uptake in chicks and rats. Steroids 70: 455-457.
98. Benjamin Rohe, Susan E. Safford, Ilka Nemere, and Mary C. Farach-Carson (2005) Identification and Characterization of 1,25D3-Membrane-Associated Rapid Response, Steroid (1,25D3 -MARRS) Binding Protein in Rat IEC-6 Cells. Steroids 70: 458-463.
99. Sutherland, S.K., Nemere, I., and Benishin, C.G. (2005) Regulation of parathyroid hypertensive factor secretion by vitamin D3 analogs in parathyroid cells derived from spontaneously hypertensive rats. J. Cellular Biochem. 96: 97-108.
100. Larsson, D., Anderson, D., Smith, N., and Nemere, I. (2006) 24,25-Dihydroxyvitamin D3 binds to catalase. J. Cellular Biochem 97: 1259-1266
101. Nemere, I., Wilson, C., Jensen, W., Steinbeck, M., Rohe, B. and Farach-Carson, M.C. (2006) Mechanism of 24,25-dihydroxyvitamin D3-Mediated inhibition of rapid, 1,25-dihydroxyvitamin D3-induced responses: role of reactive oxygen species. J Cell Biochem 99: 1572-1581.
102. Rohe, B., Safford, S., Nemere, I., Farach-Carson, M.C. (2007) Regulation of Expression of 1,25D3 –MARRS/ERp57/PDIA3 in Rat IEC-6 Cells by TGFβ and 1,25(OH)2D3. Steroids 72: 144-150.
103. Sterling, T.M. and Nemere, I. (2007) Calcium Uptake and Membrane Trafficking in Response to PTH or 25(OH)D3 in Polarized Intestinal Epithelial Cells Steroids 72: 151-157.
104. Khanal, R., Smith, N.M., and Nemere, I. (2007) Phosphate Uptake In Chick Kidney Cells: Effects Of 1,25(OH)2D3 And 24,25(OH)2D3 Steroids 72: 158-164.
105. Khanal, R., and Nemere I. (2007) Membrane receptors for vitamin D metabolites Critical Reviews in Eukaryotic Gene Expression 17: 31-47.
106. Khanal, R., and Nemere I. (2007) The ERp57/GRp58/1,25D3-MARRS receptor: Multiple functional roles in diverse cell systems. Current Medicinal Chemistry14: 1087-1093.
107. Nemere, I. (2007) The ins and outs of phosphate homeostasis. Kidney Int. 72: 135-137.
108. Peery S and Nemere I (2007) Contributions of pro-oxidant and anti-oxidant conditions to the actions of 24,25-dihydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 on phosphate uptake in intestinal cells. J Cellular Biochem 101: 1176-1184.
109. Drier R, Mainz T, Nemere I, and Bruckner P (2008) Terminal differentiation of chick embryo chondrocytes requires shedding of a cell surface protein which binds 1,25 (OH)2 vitamin D3. J Biol Chem 283: 1104-1112.
110. Nemere, I. and Hintze, K (2008) Novel hormone ‘receptors’. J Cellular Biochem 103: 401-407.
111. Khanal R and Nemere I (2008) Regulation of intestinal calcium transport. Ann Rev Nutr 28: 179-196.
Current h-index: 33
Papers in press
1. Khanal R, Sterling, TM, Smith NM, and Nemere I (2008) Membrane Receptor-Initiated Signaling in 1,25(OH)2D3-Stimulated Calcium Uptake in Intestinal Epithelial Cells. J Cell Biochem
2. Khanal R and Nemere I (2008) Endocrine Regulation of Intestinal Calcium Transport. Clinical and Experimental Pharmacology and Physiology (invited review)
Papers submitted or in preparation
1. Wu W, Roy Y, Beilhartz G, Coppolino M, Farach-Carson MC, Nemere I, and Meckling K (2008) 1,25D3-MARRS and NFkB colocalize in response to 1,25-dihydroxyvitamin D3 and co-migrate to the nuclear compartment following TPA exposure prior to monocytic differentiation of NB4 leukemia cells.
2. Tunsophon S and Nemere I (2008) Protein kinase C isotypes in signal transduction for the 1,25D3-MARRS receptor (ERp57/PDIA3) in steroid hormone stimulated phosphate uptake
3. Cynthia L. Richard, Mary C. Farach-Carson, Ben Rohe, Ilka Nemere and Kelly A. Meckling (2008) Involvement of 1,25D3-MARRS (Membrane Associated Rapid Response to Steroids), a novel vitamin D receptor, in 1,25(OH)2D3-induced growth inhibition of breast cancer
