Susan E. Leeman, Ph.D.
Department of Pharmacology
Ph.D.: Radcliffe College
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.
Srinivasan S, Leeman SE, Amar S. Beneficial dysregulation of the time course of inflammatory mediators in lipopolysaccharide-induced tumor necrosis factor alpha factor-deficient mice. Clin Vaccine Immunol. 2010 May;17(5):699-704. Epub 2010 Mar 10.
Zhou Q, Leeman SE, Amar S. Signaling mechanisms involved in altered function of macrophages from diet-induced obese mice affect immune responses. Proc Natl Acad Sci U S A. 2009 Jun 30;106(26):10740-5. Epub 2009 Jun 17
Reed KL, Stucchi AF, Leeman SE, Becker JM. Inhibitory effects of a neurokinin-1 receptor antagonist on postoperative peritoneal adhesion formation. Ann N Y Acad Sci. 2008 Nov;1144:116-26.
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 ]