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Steven A. Rosenzweig

Title
InstitutionMedical University of South Carolina
DepartmentCell and Molecular Pharmacology and Experimental Therapeutics
AddressP.O. Box MSC 509
BSB 313G
Basic Science Building - 173 Ashley Ave.
Phone843-792-5841
Fax843-792-2474
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    Collapse Overview 
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    We are studying the dysregulation of the insulin-like growth factor (IGF) system in cancer. In breast cancer and head and neck squamous cell carcinoma cells, we are examining IGF-1 receptor crosstalk to vascular endothelial growth factor (VEGF) signaling in mediating enhanced tumorigenicity and metastasis.

    Using retinal pigment epithelial cells as a model, we are studying the interplay between IGF-1 receptor signaling and hypoxia in the regulation of vascular endothelial growth factor production and the loss of intercellular tight junctions. These studies are designed to better understand the contributions of these factors to the choroidal neovascularization accompanying age-related macular degeneration.

    An underlying theme of our research is to develop inhibitors of IGF signaling. Toward this end we are employing a number of complementary strategies to develop IGF antagonists using the IGF-binding proteins (IGFBPs) as lead compounds. The IGFBPs are a class of six homologous secretory proteins, which function to block access of the IGFs to the IGF-1 receptor. For these analyses, we are using IGFBP-2 as a template for studies aimed at defining the binding domain for IGF-1. The IGFBPs interact with a specific binding domain on IGF-1 that is distinct from its receptor binding domain. These studies have profound implications for the development of IGF-1 antagonists by designing small molecular weight analogs, structurally identical to the binding site for use in inhibiting the growth of IGF-dependent tumors. These studies also have important applications toward defining the IGF-1 binding domain on the IGF-1 receptor and the development of IGF-1 receptor antagonists.

    Toward this end, we are collaborating with Professor H.S. Atreya in the Biomolecular NMR Laboratory at the Indian Institute of Science, Bangalore, India.

    Collapse keywords
    Cancer, Genetics, Growth factor dysregulation in cancer, Insulin-like growth factor (IGF) receptor crosstalk to vascular endothelial growth factor (VEGF) and metastatic signaling cascades, VEGF signaling to HEF1 and invadopodia formation, and IGF-binding protein structure and function

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    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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    1. Asampille G, Verma BK, Swain M, Shettar A, Rosenzweig SA, Kondaiah P, Atreya HS. An ultra-stable redox-controlled self-assembling polypeptide nanotube for targeted imaging and therapy in cancer. J Nanobiotechnology. 2018 Dec 08; 16(1):101. PMID: 30526620.
      View in: PubMed
    2. Semelakova M, Grauzam S, Betadthunga P, Tiedeken J, Coaxum S, Neskey DM, Rosenzweig SA. Vimentin and Non-Muscle Myosin IIA are Members of the Neural Precursor Cell Expressed Developmentally Down-Regulated 9 (NEDD9) Interactome in Head and Neck Squamous Cell Carcinoma Cells. Transl Oncol. 2019 Jan; 12(1):49-61. PMID: 30267961.
      View in: PubMed
    3. Grauzam S, Brock AM, Holmes CO, Tiedeken JA, Boniface SG, Pierson BN, Patterson DG, Coaxum SD, Neskey DM, Rosenzweig SA. NEDD9 stimulated MMP9 secretion is required for invadopodia formation in oral squamous cell carcinoma. Oncotarget. 2018 May 22; 9(39):25503-25516. PMID: 29876004.
      View in: PubMed
    4. Rosenzweig SA. Acquired Resistance to Drugs Targeting Tyrosine Kinases. Adv Cancer Res. 2018; 138:71-98. PMID: 29551130.
      View in: PubMed
    5. Coaxum SD, Tiedeken J, Garrett-Mayer E, Myers J, Rosenzweig SA, Neskey DM. The tumor suppressor capability of p53 is dependent on non-muscle myosin IIA function in head and neck cancer. Oncotarget. 2017 Apr 04; 8(14):22991-23007. PMID: 28160562.
      View in: PubMed
    6. Jezierska-Drutel A, Rosenzweig SA, Neumann CA. Role of oxidative stress and the microenvironment in breast cancer development and progression. Adv Cancer Res. 2013; 119:107-25. PMID: 23870510.
      View in: PubMed
    7. Rossa C, Sommer G, Spolidorio LC, Rosenzweig SA, Watson DK, Kirkwood KL. Loss of expression and function of SOCS3 is an early event in HNSCC: altered subcellular localization as a possible mechanism involved in proliferation, migration and invasion. PLoS One. 2012; 7(9):e45197. PMID: 23028842.
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    8. Rosenzweig SA. Acquired resistance to drugs targeting receptor tyrosine kinases. Biochem Pharmacol. 2012 Apr 15; 83(8):1041-8. PMID: 22227013.
      View in: PubMed
    9. Rosenzweig SA, Atreya HS. Defining the pathway to insulin-like growth factor system targeting in cancer. Biochem Pharmacol. 2010 Oct 15; 80(8):1115-24. PMID: 20599789.
      View in: PubMed
    10. Swain M, Slomiany MG, Rosenzweig SA, Atreya HS. High-yield bacterial expression and structural characterization of recombinant human insulin-like growth factor binding protein-2. Arch Biochem Biophys. 2010 Sep 15; 501(2):195-200. PMID: 20541521.
      View in: PubMed
    11. Lucas JT, Salimath BP, Slomiany MG, Rosenzweig SA. Regulation of invasive behavior by vascular endothelial growth factor is HEF1-dependent. Oncogene. 2010 Aug 05; 29(31):4449-59. PMID: 20498643.
      View in: PubMed
    12. Mulligan JK, Rosenzweig SA, Young MR. Tumor secretion of VEGF induces endothelial cells to suppress T cell functions through the production of PGE2. J Immunother. 2010 Feb-Mar; 33(2):126-35. PMID: 20145550.
      View in: PubMed
    13. Swain M, Thirupathi R, Krishnarjuna B, Eaton EM, Kibbey MM, Rosenzweig SA, Atreya HS. Spontaneous and reversible self-assembly of a polypeptide fragment of insulin-like growth factor binding protein-2 into fluorescent nanotubular structures. Chem Commun (Camb). 2010 Jan 14; 46(2):216-8. PMID: 20024330.
      View in: PubMed
    14. Mulligan JK, Day TA, Gillespie MB, Rosenzweig SA, Young MR. Secretion of vascular endothelial growth factor by oral squamous cell carcinoma cells skews endothelial cells to suppress T-cell functions. Hum Immunol. 2009 Jun; 70(6):375-82. PMID: 19480853.
      View in: PubMed
    15. Slomiany MG, Black LA, Kibbey MM, Tingler MA, Day TA, Rosenzweig SA. Insulin-like growth factor-1 receptor and ligand targeting in head and neck squamous cell carcinoma. Cancer Lett. 2007 Apr 18; 248(2):269-79. PMID: 16996205.
      View in: PubMed
    16. Slomiany MG, Rosenzweig SA. Hypoxia-inducible factor-1-dependent and -independent regulation of insulin-like growth factor-1-stimulated vascular endothelial growth factor secretion. J Pharmacol Exp Ther. 2006 Aug; 318(2):666-75. PMID: 16682453.
      View in: PubMed
    17. Robinson SA, Rosenzweig SA. Paradoxical effects of the phage display-derived peptide antagonist IGF-F1-1 on insulin-like growth factor-1 receptor signaling. Biochem Pharmacol. 2006 Jun 28; 72(1):53-61. PMID: 16684509.
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    18. Fornoni A, Rosenzweig SA, Lenz O, Rivera A, Striker GE, Elliot SJ. Low insulin-like growth factor binding protein-2 expression is responsible for increased insulin receptor substrate-1 phosphorylation in mesangial cells from mice susceptible to glomerulosclerosis. Endocrinology. 2006 Jul; 147(7):3547-54. PMID: 16556765.
      View in: PubMed
    19. Slomiany MG, Black LA, Kibbey MM, Day TA, Rosenzweig SA. IGF-1 induced vascular endothelial growth factor secretion in head and neck squamous cell carcinoma. Biochem Biophys Res Commun. 2006 Apr 14; 342(3):851-8. PMID: 16499871.
      View in: PubMed
    20. Kibbey MM, Jameson MJ, Eaton EM, Rosenzweig SA. Insulin-like growth factor binding protein-2: contributions of the C-terminal domain to insulin-like growth factor-1 binding. Mol Pharmacol. 2006 Mar; 69(3):833-45. PMID: 16306230.
      View in: PubMed
    21. Rosenzweig SA. What's new in the IGF-binding proteins? Growth Horm IGF Res. 2004 Oct; 14(5):329-36. PMID: 15336228.
      View in: PubMed
    22. Robinson SA, Rosenzweig SA. Synthesis and characterization of biotinylated forms of insulin-like growth factor-1: topographical evaluation of the IGF-1/IGFBP-2 AND IGFBP-3 interface. Biochemistry. 2004 Sep 14; 43(36):11533-45. PMID: 15350139.
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    23. Slomiany MG, Rosenzweig SA. IGF-1-induced VEGF and IGFBP-3 secretion correlates with increased HIF-1 alpha expression and activity in retinal pigment epithelial cell line D407. Invest Ophthalmol Vis Sci. 2004 Aug; 45(8):2838-47. PMID: 15277511.
      View in: PubMed
    24. Slomiany MG, Rosenzweig SA. Autocrine effects of IGF-I-induced VEGF and IGFBP-3 secretion in retinal pigment epithelial cell line ARPE-19. Am J Physiol Cell Physiol. 2004 Sep; 287(3):C746-53. PMID: 15140752.
      View in: PubMed
    25. Day TA, Davis BK, Gillespie MB, Joe JK, Kibbey M, Martin-Harris B, Neville B, Richardson MS, Rosenzweig S, Sharma AK, Smith MM, Stewart S, Stuart RK. Oral cancer treatment. Curr Treat Options Oncol. 2003 Feb; 4(1):27-41. PMID: 12525277.
      View in: PubMed
    26. Horney MJ, Evangelista CA, Rosenzweig SA. Synthesis and characterization of insulin-like growth factor (IGF)-1 photoprobes selective for the IGF-binding proteins (IGFBPS). photoaffinity labeling of the IGF-binding domain on IGFBP-2. J Biol Chem. 2001 Jan 26; 276(4):2880-9. PMID: 11063745.
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    27. Huang L, Shanker YG, Dubauskaite J, Zheng JZ, Yan W, Rosenzweig S, Spielman AI, Max M, Margolskee RF. Ggamma13 colocalizes with gustducin in taste receptor cells and mediates IP3 responses to bitter denatonium. Nat Neurosci. 1999 Dec; 2(12):1055-62. PMID: 10570481.
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    28. Horney MJ, Shirley DW, Kurtz DT, Rosenzweig SA. Elevated glucose increases mesangial cell sensitivity to insulin-like growth factor I. Am J Physiol. 1998 06; 274(6):F1045-53. PMID: 9841495.
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    29. Lu G, Meier KE, Jaffa AA, Rosenzweig SA, Egan BM. Oleic acid and angiotensin II induce a synergistic mitogenic response in vascular smooth muscle cells. Hypertension. 1998 Apr; 31(4):978-85. PMID: 9535424.
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    30. Jaffa AA, Miller BS, Rosenzweig SA, Naidu PS, Velarde V, Mayfield RK. Bradykinin induces tubulin phosphorylation and nuclear translocation of MAP kinase in mesangial cells. Am J Physiol. 1997 12; 273(6):F916-24. PMID: 9435680.
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    31. Zhang P, Miller BS, Rosenzweig SA, Bhat NR. Activation of C-jun N-terminal kinase/stress-activated protein kinase in primary glial cultures. J Neurosci Res. 1996 Oct 01; 46(1):114-21. PMID: 8892112.
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    32. Lu G, Morinelli TA, Meier KE, Rosenzweig SA, Egan BM. Oleic acid-induced mitogenic signaling in vascular smooth muscle cells. A role for protein kinase C. Circ Res. 1996 Sep; 79(3):611-8. PMID: 8781494.
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    33. Miller BS, Shankavaram UT, Horney MJ, Gore AC, Kurtz DT, Rosenzweig SA. Activation of cJun NH2-terminal kinase/stress-activated protein kinase by insulin. Biochemistry. 1996 Jul 02; 35(26):8769-75. PMID: 8679641.
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    34. Law NM, Rosenzweig SA. Neuronal insulin receptors in Y79 retinoblastoma cells. Biochem Biophys Res Commun. 1995 May 05; 210(1):58-66. PMID: 7741749.
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    35. Horio B, Law NM, Rosenzweig SA. Characterization of vasoactive intestinal peptide receptors in rabbit ciliary processes. Invest Ophthalmol Vis Sci. 1995 Jan; 36(1):192-9. PMID: 7529752.
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    36. Law NM, Rosenzweig SA. Characterization of the G-protein linked orphan receptor GPRN1/RDC1. Biochem Biophys Res Commun. 1994 May 30; 201(1):458-65. PMID: 8198609.
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    37. Goetzl EJ, Patel DR, Kishiyama JL, Smoll AC, Turck CW, Law NM, Rosenzweig SA, Sreedharan SP. Specific recognition of the human neuroendocrine receptor for vasoactive intestinal peptide by anti-peptide antibodies. Mol Cell Neurosci. 1994 Apr; 5(2):145-52. PMID: 7518311.
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    38. Rosenzweig SA, Oemar BS, Law NM, Shankavaram UT, Miller BS. Insulin like growth factor 1 receptor signal transduction to the nucleus. Adv Exp Med Biol. 1993; 343:159-68. PMID: 8184736.
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    39. Zetterström C, Benjamin A, Rosenzweig SA. Differential expression of retinal insulin receptors in STZ-induced diabetic rats. Diabetes. 1992 Jul; 41(7):818-25. PMID: 1612196.
      View in: PubMed
    40. Oemar BS, Law NM, Rosenzweig SA. Insulin-like growth factor-1 induces tyrosyl phosphorylation of nuclear proteins. J Biol Chem. 1991 Dec 25; 266(36):24241-4. PMID: 1662205.
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    41. Vignery A, Raymond MJ, Qian HY, Wang F, Rosenzweig SA. Multinucleated rat alveolar macrophages express functional receptors for calcitonin. Am J Physiol. 1991 Dec; 261(6 Pt 2):F1026-32. PMID: 1721493.
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    42. Dardevet D, Komori K, Grunfeld C, Rosenzweig SA, Buse MG. Increased hepatic insulin proreceptor-to-receptor ratio in diabetes: a possible processing defect. Am J Physiol. 1991 Nov; 261(5 Pt 1):E562-71. PMID: 1951680.
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    43. Zetterström C, Fang C, Benjamin A, Rosenzweig SA. Characterization of a novel receptor in toad retina with dual specificity for insulin and insulin-like growth factor I. J Neurochem. 1991 Oct; 57(4):1332-9. PMID: 1654393.
      View in: PubMed
    44. Raymond MJ, Rosenzweig SA. Vasoactive intestinal peptide receptors on AR42J rat pancreatic acinar cells. Biochem Biophys Res Commun. 1991 Aug 30; 179(1):176-82. PMID: 1652948.
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    45. Oemar BS, Foellmer HG, Hodgdon-Anandant L, Rosenzweig SA. Regulation of insulin-like growth factor I receptors in diabetic mesangial cells. J Biol Chem. 1991 Feb 05; 266(4):2369-73. PMID: 1846626.
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    46. Rosenzweig SA, Zetterström C, Benjamin A. Identification of retinal insulin receptors using site-specific antibodies to a carboxyl-terminal peptide of the human insulin receptor alpha-subunit. Up-regulation of neuronal insulin receptors in diabetes. J Biol Chem. 1990 Oct 15; 265(29):18030-4. PMID: 2211678.
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    47. Bone EA, Rosenzweig SA. Characterization of cholecystokinin receptors in toad retina. Peptides. 1988 Mar-Apr; 9(2):373-81. PMID: 3131747.
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    48. Madison LD, Jamieson JD, Rosenzweig SA. Heterogeneity of cholecystokinin receptors in pancreas. Biochem Biophys Res Commun. 1987 Mar 13; 143(2):761-7. PMID: 3105532.
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    49. Malech HL, Gardner JP, Heiman DF, Rosenzweig SA. Asparagine-linked oligosaccharides on formyl peptide chemotactic receptors of human phagocytic cells. J Biol Chem. 1985 Feb 25; 260(4):2509-14. PMID: 3919002.
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    50. Madison LD, Rosenzweig SA, Jamieson JD. Use of the heterobifunctional cross-linker m-maleimidobenzoyl N-hydroxysuccinimide ester to affinity label cholecystokinin binding proteins on rat pancreatic plasma membranes. J Biol Chem. 1984 Dec 10; 259(23):14818-23. PMID: 6094576.
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    51. Rosenzweig SA, Madison LD, Jamieson JD. Analysis of cholecystokinin-binding proteins using endo-beta-N-acetylglucosaminidase F. J Cell Biol. 1984 Sep; 99(3):1110-6. PMID: 6088554.
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    52. Miller LJ, Reilly WM, Rosenzweig SA, Jamieson JD, Go VL. The mechanisms by which dibutyryl cyclic GMP antagonizes the action of cholecystokinin. Gastroenterology. 1983 Jun; 84(6):1637-9. PMID: 6301928.
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    53. Miller LJ, Reilly WM, Rosenzweig SA, Jamieson JD, Go VL. A soluble interaction between dibutyryl cyclic guanosine 3':5'-monophosphate and cholecystokinin: a possible mechanism for the inhibition of cholecystokinin activity. Gastroenterology. 1983 Jun; 84(6):1505-11. PMID: 6301926.
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    54. Rosenzweig SA, Miller LJ, Jamieson JD. Identification and localization of cholecystokinin-binding sites on rat pancreatic plasma membranes and acinar cells: a biochemical and autoradiographic study. J Cell Biol. 1983 May; 96(5):1288-97. PMID: 6841449.
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    55. Miller LJ, Rosenzweig SA, Jamieson JD. Preparation and characterization of a probe for the cholecystokinin octapeptide receptor, N alpha (125I-desaminotyrosyl)CCK-8, and its interactions with pancreatic acini. J Biol Chem. 1981 Dec 10; 256(23):12417-23. PMID: 6271785.
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    56. Rosenzweig SA, Yip CC. Preparation of beta-cells from fetal bovine pancreas: characterization of insulin biosynthetic activity. Can J Biochem. 1979 Jun; 57(6):480-8. PMID: 383231.
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    57. Tung AK, Rosenzweig SA, Foa PP. Glucagon from avian pancreatic islets: radioreceptor studies. Can J Biochem. 1977 Aug; 55(8):915-8. PMID: 329956.
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    58. Tung AK, Rosenzweig SA, Foà PP. Glucagon from avian pancreatic islets: purification and partial characterization of a 9000-dalton species with glucagon immunoreactivity. Proc Soc Exp Biol Med. 1976 Nov; 153(2):344-9. PMID: 63126.
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