SUSAN E. LEEMAN, Ph.D.
SUSAN E. LEEMAN, Ph.D.
Professor
Department of Pharmacology
Office: L-611
Phone: 617-638-4364
Fax: 617-638-4329
Email: sleeman@bu.edu
Ph.D.: Radcliffe College
Research Interests:
PHYSIOLOGICAL FUNCTIONS OF THE NEUROPEPTIDES SUBSTANCE P AND NEUROTENSIN
Our work focuses on the two peptides, substance P (SP) and neurotensin, that were isolated and chemically defined in this laboratory. Previous projects that are currently underway relating to the biochemistry and pharmacology of SP include studies to determine the binding domains of SP with its receptor using photoactivatable derivatives of SP containing the photoreactive amino acid benzoylphenlalanine; studies to determine the binding domains of an antagonist of SP, CP 96,345 using a photoactivatable derivative of this compound; the characterization of calcium signals generated by administration of SP to CHO cells transfected with mRNA encoding the full-length SP receptor; the roles of SP in several models of inflammation in the gastrointestinal tract using non-peptide SP antagonists; a truncated form of the SP receptor and several mutant receptors. A new direction of research involves studies directed towards the chemical characterization and function of the carbohydrate moieties on the SP receptor.
Selected Publications:
Lai JP, Lai S, Tuluc F, Tansky MF, Kilpatrick LE, Leeman SE, Douglas SE. Differences in the length of the carboxyl teminus mediate functional properties of neurokinin-1 receptor. Proc Natl Acad Sci USA. 2008 Aug 19 [Epub ahead of print].
Lim R, Morrill JM, Prushik SG, Reed KL, Gower AC, Leeman SE, Stucchi AF, Becker JM. An FDA Approved Neurokinin-1 Receptor Antagonists is Effective in Reducing Intraabdominal Adhesions when Administered Intrperitoneally, But Not Orally. J. Gastrointest Surg. 2008 Aug 16 [Epub ahead of print].
Chen CD, Podvin S, Gillespie E, Leeman SE, Abraham CR. Insulin stimulates the cleavage and release of the extracellular domain of Klotho by ADAM10 and ADAM17. Proc Natl Acad Sci U S A. 2007 Dec 11;104(50):19796-801. Epub 2007 Dec 3.
Cohen PA, Gower AC, Stucchi AF, Leeman SE, Becker JM, Reed KL. A neurokinin-1 receptor antagonist that reduces intraabdominal adhesion formation increases peritoneal matrix metalloproteinase activity. Wound Repair Regen. 2007 Nov-Dec;15(6):800-8.
Tansky MF, Pothoulakis C, Leeman SE. Functional consequences of alteration of N-linked glycosylation sites on the neurokinin 1 receptor. Proc Natl Acad Sci U S A. 2007 Jun 19;104(25):10691-6. Epub 2007 Jun 11.
Singh AJ, Meyer RD, Navruzbekov G, Shelke R, Duan L, Band H, Leeman SE, Rahimi N. A critical role for the E3-ligase activity of c-Cbl in VEGFR-2-mediated PLCgamma1 activation and angiogenesis. Proc Natl Acad Sci U S A. 2007 Mar 27;104(13):5413-8. Epub 2007 Mar 19.
Prushik SG, Aarons CB, Matteotti R, Reed KL, Gower AC, Leeman SE, Stucchi AF, Becker JM. A neurokinin 1 receptor antagonist decreases adhesion reformation after laparoscopic lysis of adhesions in a rat model of adhesion formation. Surg Endosc. 2007 Oct;21(10):1790-5. Epub 2007 Mar 14.
Cohen PA, Aarons CB, Gower AC, Stucchi AF, Leeman SE, Becker JM, Reed KL. The effectiveness of a single intraperitoneal infusion of a neurokinin-1 receptor antagonist in reducing postoperative adhesion formation is time dependent. Surgery. 2007 Mar;141(3):368-75. Epub 2007 Feb 6.
Aarons CB, Cohen PA, Gower A, Reed KL, Leeman SE, Stucchi AF, Becker JM. Statins (HMG-CoA reductase inhibitors) decrease postoperative adhesions by increasing peritoneal fibrinolytic activity. Ann Surg. 2007 Feb;245(2):176-84.
Karagiannides I, Kokkotou E, Tansky M, Tchkonia T, Giorgadze N, O’Brien M, Leeman SE, Kirkland JL, Pothoulakis C. nduction of colitis causes inflammatory responses in fat depots: evidence for substance P pathways in human mesenteric preadipocytes. Proc Natl Acad Sci U S A. 2006 Mar 28;103(13):5207-12. Epub 2006 Mar 20.
Tang X, Marciano DL, Leeman SE, Amar S. (2005) LPS induces the interaction of a transcription factor, LPS-induced TNF-alpha factor, and STAT6(B) with effects on multiple cytokines. Proc Natl Acad Sci U S A. 2005 Apr 5;102(14):5132-7. Epub 2005 Mar 25. [ Abstract ]
Reed KL, Fruin AB, Gower AC, Stucchi AF, Leeman SE, Becker JM. (2004) A neurokinin 1 receptor antagonist decreases postoperative peritoneal adhesion formation and increases peritoneal fibrinolytic activity. Proc Natl Acad Sci U S A. 2004 Jun 15;101(24):9115-20. Epub 2004 Jun 8. [ Abstract ]
Stucchi AF, Shebani KO, Leeman SE, Wang CC, Reed KL, Fruin AB, Gower AC, McClung JP, Andry CD, O’Brien MJ, Pothoulakis C, Becker JM. (2003) A neurokinin 1 receptor antagonist reduces an ongoing ileal pouch inflammation and the response to a subsequent inflammatory stimulus. Am J Physiol Gastrointest Liver Physiol. 2003 Dec;285(6):G1259-67. Epub 2003 Jul 31. [ Abstract ]
Kennedy PG, Rodgers J, Bradley B, Hunt SP, Gettinby G, Leeman SE, de Felipe C, Murray M. (2003) Clinical and neuroinflammatory responses to meningoencephalitis in substance P receptor knockout mice. Brain. 2003 Jul;126(Pt 7):1683-90. Epub 2003 Jun 4. [ Abstract ]
Reed KL, Fruin AB, Bishop-Bartolomei KK, Gower AC, Nicolaou M, Stucchi AF, Leeman SE, Becker JM. (2002) Neurokinin-1 receptor and substance P messenger RNA levels increase during intraabdominal adhesion formation. J Surg Res. 2002 Nov;108(1):165-72. [ Abstract ]
Bremer AA, Tansky MF, Wu M, Boyd ND, Leeman SE. (2001) Direct evidence for the interaction of neurokinin A with the tachykinin NK(1) receptor in tissue. Eur J Pharmacol. 2001 Jul 6;423(2-3):143-7. [ Abstract ]
Macdonald D, Mierke DF, Li H, Pellegrini M, Sachais B, Krause JE, Leeman SE, Boyd ND. (2001) Photoaffinity labeling of mutant neurokinin-1 receptors reveals additional structural features of the substance P/NK-1 receptor complex. Biochemistry. 2001 Feb 27;40(8):2530-9. [ Abstract ]
Bremer AA, Leeman SE, Boyd ND. (2001) Evidence for spatial proximity of two distinct receptor regions in the substance P (SP)*neurokinin-1 receptor (NK-1R) complex obtained by photolabeling the NK-1R with p-benzoylphenylalanine3-SP. J Biol Chem. 2001 Jun 22;276(25):22857-61. Epub 2001 Apr 9. [ Abstract ]
Li H, Macdonald DM, Hronowski X, Costello CE, Leeman SE, Boyd ND. (2000) Further definition of the substance P (SP)/neurokinin-1 receptor complex. MET-174 is the site of photoinsertion p-benzoylphenylalanine4 SP. J Biol Chem. 2001 Apr 6;276(14):10589-93. Epub 2000 Dec 14. [ Abstract ]
Bremer AA, Leeman SE, Boyd ND. (2000) The common C-terminal sequences of substance P and neurokinin A contact the same region of the NK-1 receptor. FEBS Lett. 2000 Dec 1;486(1):43-8. [ Abstract ]
Berg EA, Johnson RJ, Leeman SE, Boyd N, Kimerer L, Fine RE. (2000) Isolation and characterization of substance P-containing dense core vesicles from rabbit optic nerve and termini. J Neurosci Res. 2000 Dec 15;62(6):830-9. [ Abstract ]
Leeman SE, Ferguson SL. (2000) Substance P: an historical perspective. Neuropeptides. 2000 Oct;34(5):249-54. No abstract available. [ Abstract ]
Alexander MJ, Leeman SE. (1998) Widespread expression in adult rat forebrain of mRNA encoding high-affinity neurotensin receptor. J Comp Neurol. 1998 Dec 28;402(4):475-500. [ Abstract ]
Pothoulakis C, Castagliuolo I, Leeman SE, Wang CC, Li H, Hoffman BJ, Mezey E. (1998) Substance P receptor expression in intestinal epithelium in clostridium difficile toxin A enteritis in rats. Am J Physiol. 1998 Jul;275(1 Pt 1):G68-75. [ Abstract ]
Pothoulakis C, Castagliuolo I, Leeman SE. (1998) Neuroimmune mechanisms of intestinal responses to stress. Role of corticotropin-releasing factor and neurotensin. Ann N Y Acad Sci. 1998 May 1;840:635-48. Review. [ Abstract ]
Thoidis G, Chen P, Pushkin AV, Vallega G, Leeman SE, Fine RE, Kandror KV. (1998) Two distinct populations of synaptic-like vesicles from rat brain. Proc Natl Acad Sci U S A. 1998 Jan 6;95(1):183-8. [ Abstract ]
Li H, Leeman SE, Slack BE, Hauser G, Saltsman WS, Krause JE, Blusztajn JK, Boyd ND. (1997) A substance P (neurokinin-1) receptor mutant carboxyl-terminally truncated to resemble a naturally occurring receptor isoform displays enhanced responsiveness and resistance to desensitization. Proc Natl Acad Sci U S A. 1997 Aug 19;94(17):9475-80. [ Abstract ]
Castagliuolo I, Keates AC, Qiu B, Kelly CP, Nikulasson S, Leeman SE, Pothoulakis C. (1997) Increased substance P responses in dorsal root ganglia and intestinal macrophages during Clostridium difficile toxin A enteritis in rats. Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4788-93. [ Abstract ]
Kennedy PG, Rodgers J, Jennings FW, Murray M, Leeman SE, Burke JM. (1997) A substance P antagonist, RP-67,580, ameliorates a mouse meningoencephalitic response to Trypanosoma brucei brucei. Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):4167-70. [ Abstract ]
Kohlmann O Jr, Cesaretti ML, Ginoza M, Tavares A, Zanella MT, Ribeiro AB, Ramos OL, Leeman SE, Gavras I, Gavras H. (1997) Role of substance P in blood pressure regulation in salt-dependent experimental hypertension. Hypertension. 1997 Jan;29(1 Pt 2):506-9. [ Abstract ]
Castagliuolo I, Leeman SE, Bartolak-Suki E, Nikulasson S, Qiu B, Carraway RE, Pothoulakis C. (1997) A neurotensin antagonist, SR 48692, inhibits colonic responses to immobilization stress in rats. Proc Natl Acad Sci U S A. 1996 Oct 29;93(22):12611-5. [ Abstract ]
Kage R, Leeman SE, Krause JE, Costello CE, Boyd ND. (1996) Identification of methionine as the site of covalent attachment of a p-benzoyl-phenylalanine-containing analogue of substance P on the substance P (NK-1) receptor. J Biol Chem. 1996 Oct 18;271(42):25797-800. [ Abstract ]
Fisher CE, Sutherland JA, Krause JE, Murphy JR, Leeman SE, vanderSpek JC. (1996) Genetic construction and properties of a diphtheria toxin-related substance P fusion protein: in vitro destruction of cells bearing substance P receptors. Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):7341-5. [ Abstract ]
Rittenhouse PA, Markle RA, Marchand JE, Kream RM, Leeman SE. (1996) Streptozotocin-induced diabetes produces a decrease in pituitary substance P content and preprotachykinin mRNA. Neurosci Lett. 1996 Jun 21;211(2):77-80. [ Abstract ]
Zhu GF, Chancellor-Freeland C, Berman AS, Kage R, Leeman SE, Beller DI, Black PH. (1996) Endogenous substance P mediates cold water stress-induced increase in interleukin-6 secretion from peritoneal macrophages. J Neurosci. 1996 Jun 1;16(11):3745-52. [ Abstract ]
MacDonald D, Silberman SC, Lowe JA 3rd, Drozda SE, Leeman SE, Boyd ND. (1996) Photoaffinity labeling of the human substance P (neurokinin-1) receptor with [3H2]azido-CP-96,345, a photoreactive derivative of a nonpeptide antagonist. Mol Pharmacol. 1996 May;49(5):808-13. [ Abstract ]
Li H, Hsu P, Sachais BS, Krause JE, Leeman SE, Boyd ND. (1996) Identification of the site in the substance P (NK-1) receptor for modulation of peptide binding by sulfhydryl reagents. J Biol Chem. 1996 Jan 26;271(4):1950-6. [ Abstract ]
Boyd ND, Kage R, Dumas JJ, Krause JE, Leeman SE. (1996) The peptide binding site of the substance P (NK-1) receptor localized by a photoreactive analogue of substance P: presence of a disulfide bond. Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):433-7. [ Abstract ]
Rittenhouse PA, Marchand JE, Chen J, Kream RM, Leeman SE. (1996) Streptozotocin-induced diabetes is associated with altered expression of peptide-encoding mRNAs in rat sensory neurons. Peptides. 1996;17(6):1017-22. [ Abstract ]
Chancellor-Freeland C, Zhu GF, Kage R, Beller DI, Leeman SE, Black PH. (1995) Substance P and stress-induced changes in macrophages. Ann N Y Acad Sci. 1995 Dec 29;771:472-84. Review. [ Abstract ]
Kohlmann O Jr, Ginoza M, Cezaretti ML, Zanella MT, Ribeiro AB, Tavares A, Ramos OL, Leeman SE, Gavras I, Gavras H. (1995) Cardiovascular effects of a specific nonpeptide antagonist of substance P (NK-1) receptor in DOCA-salt hypertension. Hypertension. 1995 Dec;26(6 Pt 2):1186-9. [ Abstract ]
Boyd ND, Kage R, Dumas JJ, Silberman SC, Krause JE, Leeman SE. (1995) Localization of the peptide binding domain of the NK-1 tachykinin receptor using photoreactive analogues of substance P. Ann N Y Acad Sci. 1995 May 10;757:405-9. No abstract available. [ Abstract ]
Amaratunga A, Leeman SE, Kosik KS, Fine RE. (1995) Inhibition of kinesin synthesis in vivo inhibits the rapid transport of representative proteins for three transport vesicle classes into the axon. J Neurochem. 1995 May;64(5):2374-6. [ Abstract ]
Kage R, Hershey AD, Krause JE, Boyd ND, Leeman SE. (1995) Characterization of the substance P (NK-1) receptor in tunicamycin-treated transfected cells using a photoaffinity analogue of substance P. J Neurochem. 1995 Jan;64(1):316-21. [ Abstract ]
Vijayan E, Carraway R, Leeman SE, McCann SM. (1994) Physiological significance of neurotensin in pituitary glycoprotein hormone release as revealed by in vivo and in vitro studies with neurotensin antiserum. Neuroendocrinology. 1994 Aug;60(2):157-64. [ Abstract ]
Alexander MJ, Leeman SE. (1994) Estrogen-inducible neurotensin immunoreactivity in the preoptic area of the female rat. J Comp Neurol. 1994 Jul 22;345(4):496-509. [ Abstract ]
Pothoulakis C, Castagliuolo I, LaMont JT, Jaffer A, O’Keane JC, Snider RM, Leeman SE. (1994) CP-96,345, a substance P antagonist, inhibits rat intestinal responses to Clostridium difficile toxin A but not cholera toxin. Proc Natl Acad Sci U S A. 1994 Feb 1;91(3):947-51. [ Abstract ]
Luber-Narod J, Kage R, Leeman SE. (1994) Substance P enhances the secretion of tumor necrosis factor-alpha from neuroglial cells stimulated with lipopolysaccharide. J Immunol. 1994 Jan 15;152(2):819-24. [ Abstract ]
Lantz RC, Lemen RJ, Dey RD, Rodd A, Bowers M, Chen H, Witten ML, Quan SF, Kage R, Leeman SE. (1993) Nedocromil preserves neuropeptides in neurons associated with airway smooth muscle and reduces adenovirus-induced airway hyperreactivity. Regul Pept. 1993 Jul 2;46(1-2):211-3. No abstract available. [ Abstract ]
Kage R, Leeman SE, Boyd ND. (1993) Biochemical characterization of two different forms of the substance P receptor in rat submaxillary gland. J Neurochem. 1993 Jan;60(1):347-51. [ Abstract ]
Leeman SE, Munson PL. (1992) Thoughts concerning women in science. FASEB J. 1992 Dec;6(15):3327. No abstract available. [ Abstract ]
Shamgochian MD, Leeman SE. (1992) Substance P stimulates luteinizing hormone secretion from anterior pituitary cells in culture. Endocrinology. 1992 Aug;131(2):871-5. [ Abstract ]
Jonassen JA, Mullikin-Kilpatrick D, Hoogasian J, Benoit SE, Leeman SE. (1992) Regulation of adenohypophyseal messenger RNAs in female rats by age, hypothyroidism, estradiol and neonatal androgenization. Mol Cell Endocrinol. 1992 Mar;84(1-2):55-64. [ Abstract ]
Alexander MJ, Leeman SE. (1992) Neurotensin gene expression in the rat preoptic area. Implications for the regulation of reproduction. Ann N Y Acad Sci. 1992;668:70-89. Review. No abstract available. [ Abstract ]
Snider RM, Longo KP, Drozda SE, Lowe JA 3rd, Leeman SE. (1991) Effect of CP-96,345, a nonpeptide substance P receptor antagonist, on salivation in rats. Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10042-4. [ Abstract ]
Chung ES, Leeman SE, Cuenoud HF. (1991) The effect of neonatal treatment with capsaicin on focal arteriolar insudation. Microvasc Res. 1991 Nov;42(3):316-24. [ Abstract ]
Alexander MJ, Kiraly ZJ, Leeman SE. (1991) Sexually dimorphic distribution of neurotensin/neuromedin N mRNA in the rat preoptic area. J Comp Neurol. 1991 Sep 1;311(1):84-96. [ Abstract ]
Morin PJ, Liu NG, Johnson RJ, Leeman SE, Fine RE. (1991) Isolation and characterization of rapid transport vesicle subtypes from rabbit optic nerve. J Neurochem. 1991 Feb;56(2):415-27. [ Abstract ]
Boyd ND, White CF, Cerpa R, Kaiser ET, Leeman SE. (1991) Photoaffinity labeling the substance P receptor using a derivative of substance P containing p-benzoylphenylalanine. Biochemistry. 1991 Jan 15;30(2):336-42. [ Abstract ]
Morin PJ, Johnson RJ, Shachar I, Fine RE, Leeman SE. (1991) Characteristics of tachykinin transport vesicles in the optic nerve. Ann N Y Acad Sci. 1991;632:442-3. No abstract available. [ Abstract ]
Jonassen JA, Leeman SE. (1991) Developmental and hormonal regulation of the sex difference in preprotachykinin gene expression in rat anterior pituitaries. Ann N Y Acad Sci. 1991;632:1-9. No abstract available. [ Abstract ]
Boyd ND, MacDonald SG, Kage R, Luber-Narod J, Leeman SE. (1991) Substance P receptor. Biochemical characterization and interactions with G proteins. Ann N Y Acad Sci. 1991;632:79-93. No abstract available. [ Abstract ]
