My research is in the area of biochemistry, specifically, the relation of structure to function in proteins. For the past several years, I have focused on proteases and peptidases, i.e., enzymes which degrade other proteins, and inhibitors for those enzymes. Current projects focus on the enzyme thimet oligopeptidase (TOP), which terminates the signal of bioactive peptides, and other neuropeptidases. For structural studies, we collaborate with Jeff Sigman at St. Mary's College and Marc Glucksman at Rosalind Franklin University. Together with Marc Tetel's lab in the Wellesley College Neuroscience Program, we have investigated the control of the enzyme in brain, especially in response to steroid hormones. Ongoing projects are focused on control of these enzymes in prostate cancer cells.
Thimet oligopeptidase (Ray, K., Hines, C.S., Coll-Rodriguez, J., Rodgers, D.W. J.Biol.Chem,.2004 , 279, 20480-20489), a metalloenzyme involved in neuroendocrine pathways and blood pressure regulation
Cells in the medial preoptic area (mPOA, panels A-C) and ventrolateral portion of the ventromedial hypothalamic nucleus (VMNvl, panels D-F) coexpress TOP (red) and ERα (green) from a control animal. TOP alone (A and D), ERα alone (B and E) and overlaid image of cells expressing both TOP and ERα (C and F).Cells in the mPOA and VMNvl expressing TOP only (red arrows), ERα only (green arrows) and both TOP and ERα (yellow arrows).
Sigman JA, *Patwa TH, *Tablante AV, *Joseph CD, Glucksman MJ, and Wolfson AJ (2005) Flexibility in substrate recognition by thimet oligopeptidase as revealed by denaturation studies. Biochem J 388: 255-261.
Kolodny NH, *Bauer D, *Bryce K, *Klucevsek K, *Lane A, *Medeiros L, *Mercer W, *Moin S, *Park D, *Peterson J, *Wright J, *Yuen C, Wolfson AJ, and Allen MM (2006) The effect of nitrogen source on cyanophycin synthesis in Synechocystis sp. Stain 6308 J Bacteriol 188: 934-940.
Bruce LA, Sigman JA, *Randall D, *Rodriguez S, *Song MM, *Dai Y, Elmore DE, Pabon A, Glucksman MJ, and Wolfson AJ (2008) Hydrogen bond residue positioning in the 599-611 loop of thimet oligopeptidase is required for substrate selection. FEBS J 276: 5607-5617.
Cyr NE, *Kua LH, Bruce LA, Chadwick JG, Tetel MJ, and Wolfson AJ (2010) Nuclear thimet oligopeptidase is coexpressed with oestrogen receptor alpha in hypothalamic cells and regulated by oestradiol in female mice. J Neuroendocrinol. 22: 936-943.
Bruce LA, Cyr NE, *Qiao JW, *DeFries CC, Tetel MJ and Wolfson AJ (2012) Neuropeptidase activity is down-regulated by estradiol in steroid-sensitive regions of the hypothalamus in female mice. Neuropeptides (in press).
Wolfson AJ, Cyr NE, Bruce LA, *Qiao JW, *DeFries CC, and Tetel MJ (2012) Regulation of neuropeptidases involved in reproductive physiology by estradiol. In: Estrogen Receptors: Mechanism, Structure, and Role in Disease (CC CHen, ed), Nova Science Publishers, Hauppauge NY (in press).
Recent research poster presentations (* indicates undergraduate co-author):
*Moin SS, *Park D, Allen MM, and Wolfson AJ (2005) Regulation of nitrate reductase
activity in a unicellular organism. Experimental Biology Annual Meeting, San
Diego CA, Abs. 509.2
*Stadelmann LE, *Leong R, *Mann-Stadt CF, *Kannabiran DR, Glucksman MJ, Sigman JA, and Wolfson AJ (2005) Lowered flexibility in thimet oligopeptidase (EC126.96.36.199) leads to a change in substrate specificity. Experimental Biology Annual Meeting, San Diego CA, Abs. 528.8
Wolfson AJ, Sigman JA, *Stadelmann LE, *Leong R, *Mann-Stadt CF , *Kannabiran DR, and Glucksman MJ (2005) Substrate Specificity of Thimet Oligopeptidase (EC188.8.131.52) Depends on Loop Flexibility. International Union of Biochemistry Meeting, Budapest, Hungary, Abs. B4-019P.
*Randall D, Sigman JA, *Song M, *Hayes G, Bruce L, Glucksman JA, and Wolfson AJ (2006) Loop region 599-611 determines substrate specificity in thimet oligopeptidase. Experimental Biology Annual Meeting, San Franciso CA, Abs. 75.8
*Srikanthan MR, *Song MM, Bruce LA, *Kua LH, Pabon A, Glucksman MJ, Sigman JA, Elmore DE, and Wolfson AJ (2007) Neuropeptide substrate specificity in thimet oligopeptidase is conferred by glycine residues residing in a loop region. Experimental Biology Annual Meeting, Washington DC, Abs. 805.6
*Kua LH, Cyr NE, Tetel MJ, Chadwick JG, Bruce LA, and Wolfson AJ (2008) Effect of estrogens and progesterone on the distribution and activity of thimet oligopeptidase in rat and mouse brain. Experimental Biology Annual Meeting, San Diego CA Abs. 837.1
*Song MM, Elmore, Sigman JA, Bruce LA, Pabon A, Glucksman MJ, and Wolfson AJ (2008) The 599-611 loop in thimet oligopeptidase modulates substrate selection via hydrogen bonding. Experimental Biology Annual Meeting, San Diego CA Abs. 793.1
*Scognamilla LA, Sigman JA, Glucksman MJ, and Wolfson AJ (2009) Evidence for a conformational change in thimet oligopeptidase and the machinery behind it. Experimental Biology Annual Meeting, New Orleans LA Abs. 502.5
*Dai Y, Cyr NE, Tetel MJ, *Kua LH, Chadwick JG, Bruce LA, and Wolfson AJ (2009) Estradiol regulation and activity of thimet oligopeptidase in the hypothalamus of female mice. Experimental Biology Annual Meeting, New Orleans Abs. 703.5
*Qiao JW, Cyr NE, Bruce LA, Tetel MJ, and Wolfson AJ (2010) Estradiol regulates neuropeptidase activity in hypothalamic regions involved in regulating gonadotropin-releasing hormone.Experimental Biology Annual Meeting, Anaheim CA Abs. 858.2
*Dhawan T, *Qiao JW, *Selen D, Bruce LA, Tetel MJ, and Wolfson AJ (2011) Effects of the neuropeptidase thimet oligopeptidase on testicular development and testosterone production. Experimental Biology Annual Meeting, Washington DC, Abs. 520.5
*DeFries CC, *Lie Y, Bruce LA, *Gambe RG, *Belyaneh NS, Tetel MJ, and Wolfson AJ (2012) Regulation of levels and localization of peptidases in prostate cancer cells by steroid hormones. Experimental Biology Annual Meeting, San Diego CA, Abs. 956.7
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