I arrived at BUSM as a junior faculty member in the biochemistry department in May, 1969, after four years of predoctoral training at Tufts Medical School and a subsequent three year postdoctoral experience at Harvard Medical School. My training and interests were focused on the chemical mechanisms, structures and specificity determinants of enzymes. The research I conducted during my 40 year career at BUSM was primarily concerned with those aspects of lysyl oxidase (LOX), an enzyme discovered just prior to my arrival at BUSM by investigators at the National Institute for Dental Research. LOX proved to be the critical catalyst that initiated the formation of inter- and intramolecular stabilizing crosslinkages in collagen and elastin. My laboratory established a method for the purification of LOX and subsequently characterized its catalytic mechanism and the electrostatic forces which contributed to its surprisingly broad substrate specificity that we had noted. Highly talented pre- and postdoctoral members of my lab cloned and thereby determined the amino acid sequence of LOX; discovered and analyzed the mechanisms whereby a variety of small organic molecules strongly inhibited this enzyme, one class of which was selected for patent protection as an anti-fibrotic agent; characterized the regulation of LOX by growth factors and other effectors; and found that LOX was a highly potent chemokine, strongly attracting vascular smooth muscle cell and other cell types as it oxidized growth factor receptors on the surface of those cells. The sequence of LOX which we had published proved to be critical to the later discovery by investigators at the Armed Forces Medical School in Bethesda that a newly found gene product that repressed of RAS-mediated carcinogenic transformation of fibroblasts was, surprisingly, lysyl oxidase. All of these studies were generously and continuously supported by several NIH grants, one of which was awarded as a distinguished MERIT award.
While I began my stay at BUSM as an Assistant Research Professor, my status was changed to the Associate Professor level In 1972 and approximately five years later, to full Professor of Biochemistry.
I also served as the Chair of two different Gordon Conferences and as invited speaker at several academic and industrial institutions, nationally and internationally. I am grateful to BUSM and, especially, to the Department of Biochemistry, for the strong support given to me and the many friendships that my experience there provided.
- Tufts University School of Medicine, PhD
- University of Massachusetts Amherst, MS
- University of Massachusetts Amherst, BS
- Published on 10/12/2018
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- Published on 4/21/2011
Lucero HA, Mäki JM, Kagan HM. Activation of cellular chemotactic responses to chemokines coupled with oxidation of plasma membrane proteins by lysyl oxidase. J Neural Transm. 2011 Jul; 118(7):1091-9. PMID: 21509606.
- Published on 12/1/2010
Grimsby JL, Lucero HA, Trackman PC, Ravid K, Kagan HM. Role of lysyl oxidase propeptide in secretion and enzyme activity. J Cell Biochem. 2010 Dec 1; 111(5):1231-43. PMID: 20717923.
- Published on 6/27/2008
Lucero HA, Ravid K, Grimsby JL, Rich CB, DiCamillo SJ, Mäki JM, Myllyharju J, Kagan HM. Lysyl oxidase oxidizes cell membrane proteins and enhances the chemotactic response of vascular smooth muscle cells. J Biol Chem. 2008 Aug 29; 283(35):24103-17. PMID: 18586678.
- Published on 1/9/2008
Yang D, Koupenova M, McCrann DJ, Kopeikina KJ, Kagan HM, Schreiber BM, Ravid K. The A2b adenosine receptor protects against vascular injury. Proc Natl Acad Sci U S A. 2008 Jan 15; 105(2):792-6. PMID: 18184815.
- Published on 10/1/2006
Lucero HA, Kagan HM. Lysyl oxidase: an oxidative enzyme and effector of cell function. Cell Mol Life Sci. 2006 Oct; 63(19-20):2304-16. PMID: 16909208.
- Published on 9/1/2005
Vadasz Z, Kessler O, Akiri G, Gengrinovitch S, Kagan HM, Baruch Y, Izhak OB, Neufeld G. Abnormal deposition of collagen around hepatocytes in Wilson's disease is associated with hepatocyte specific expression of lysyl oxidase and lysyl oxidase like protein-2. J Hepatol. 2005 Sep; 43(3):499-507. PMID: 16023247.
- Published on 12/15/2004
Gilad GM, Kagan HM, Gilad VH. Evidence for increased lysyl oxidase, the extracellular matrix-forming enzyme, in Alzheimer's disease brain. Neurosci Lett. 2005 Mar 16; 376(3):210-4. PMID: 15721223.
- Published on 8/1/2004
Jones MR, Zhao Z, Sullivan CP, Schreiber BM, Stone PJ, Toselli PA, Kagan HM, Cohen RA, Ravid K. A(3) adenosine receptor deficiency does not influence atherogenesis. J Cell Biochem. 2004 Aug 1; 92(5):1034-43. PMID: 15258925.
- Published on 4/1/2003
Jeay S, Pianetti S, Kagan HM, Sonenshein GE. Lysyl oxidase inhibits ras-mediated transformation by preventing activation of NF-kappa B. Mol Cell Biol. 2003 Apr; 23(7):2251-63. PMID: 12640111.
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