Faculty Affairs: Faculty Interests Database
A. Sue Menko, PhD

Pathology, Anatomy & Cell Biology
Professor
Vice Chair, Anatomy
Director, Wills Vision Research Center at Jefferson

Mailing Address Contact Information
1020 Locust Street JAH 564
Philadelphia, Pennsylvania 19107
United States
Phone: (215) 503-2166
Fax: (215) 923-3808
sue.menko@jefferson.edu
Qualifications
Ph.D., University of Pennsylvania, 1978

Expertise and Research Interests
My laboratory studies how receptor-signaling pathways instruct an undifferentiated cell to obtain its differentiated phenotype and those signals responsible for organizing differentiating cells into a three-dimensional functional structure - a process in development know as morphogenesis. We address how these features of differentiation and morphogenesis apply to tissue regeneration. In addition, there is now a strong focus in our lab on the mechanisms of wound healing and fibrosis. These studies are focused the role of repair cells in directing normal wound healing and how this cell population can go astray and lead to disease states, particularly fibrosis, as in the post-cataract surgery disease PCO.

Specific projects include:

The role of the alpha6 integrin receptor as an upstream regulator of survival pathways that permit caspase-3, activated downstream of a classical mitochondrial death pathway, to function as a molecular switch in the initiation of differentiation.

How coordinate signaling between integrins and growth factor receptor signaling pathways provide specificity to integrin signaling during differentiation initiation.

The role of adhesion receptors in regulating the function of actin and intermediate filament cytoskeletons to drive morphogenesis during development.

Integrin-cadherin cross-talk in cell differentiation.

Mechanisms of wound healing - studies of a unique repair cell population that regulates wound healing of epithelia.

Studies of wound healing repair cells as the source of fibrotic disease.
Industrial Relevance
My laboratory is involved in developing therapeutics to block the induction of Posterior Capsule Opacification (PCO) and cataract. These studies are focused on targeting signaling pathways we have shown are involved in the development of these diseases.
Keywords
Cadherin; Cataract Signaling Pathways; Cell Adhesion Molecules; Cell Differentiation; Cell-Cell Interaction; Cell-Matrix Interaction; Cytoskeleton; Development; Extracellular Matrix; Growth Factor Receptor; Integrin Receptor Signaling; Lens Differentiation; Protein Tyrosine Kinases; Signal Transduction; Signaling; Src Kinases
Publications
  • Pubmed
  • Leonard M, Zhang L, Zhai N, Cader A, Chan Y, Nowak RB, Fowler VM, Menko AS. 2010 Modulation of N-cadherin junctions and their role as epicenters of differentiation-specific actin regulation in the developing lens.Dev Biol. 2011 Jan 15;349(2):363-77. Epub 2010 Oct 20. PMID: 20969840.
  • Menko AS, Andley UP. 2010 ±A-Crystallin associates with ±6 integrin receptor complexes and regulates cellular signaling. Exp Eye Res. Nov;91(5):640-51. Epub 2010 Aug 13. PMID: 20709056.
  • Walker JL, Zhai N, Zhang L, Bleaken BM, Wolff I, Gerhart J, George-Weinstein M, Menko AS. 2010 Unique precursors for the mesenchymal cells involved in injury response and fibrosis. Proc Natl Acad Sci U S A. Aug 3;107(31):13730-5. Epub 2010 Jul 15. PMID: 20634425.
  • Gerhart J, Pfautz J, Neely C, Elder J, DuPrey K, Menko AS, Knudsen K, George-Weinstein M. 2009 Noggin producing, MyoD-positive cells are crucial for eye development. Dev Biol. 2009 Dec 1;336(1):30-41. Epub 2009 Sep 22. PMID: 19778533.
  • Nita-Lazar, M., Noonan, V., Rebustini, I., Walker, J., Menko A.S., and Kukuruzinska, M.A. 2009 Overexpression of DPAGT1 leads to aberrant N-glycosylation of E-cadherin and cellular discohesion in oral cancer. Cancer Res. 69:5673-80.
  • Walker, J.L., Menko, A.S., Khalil, S., Rebustini, I., Hoffman, M.P, Kreidberg, J.A. and Kukuruzinska, M.A. 2008 Diverse roles of E-cadherin in the morphogenesis of the submandibular gland: Insights into the formation of acinar and ductal structures. Dev. Dyn. 237:3128-41.
  • Walker, J., and Menko, A.S. 2008 Integrins in lens development and disease. Exp Eye Res. 2009 88:216-25.
  • Leonard, M., Chan, Y., and Menko, A.S. 2008 Identification of a novel intermediate filament-linked N-cadherin/gamma-catenin complex involved in the establishment of the cytoarchitecture of differentiated lens fiber cells. Dev Biol. 319:298-308.
  • Xi, J.H., Bai, F., Gross, J., Townsend, R.R., Menko, A.S., and Andley, U.P. 2008 Mechanism of small heat shock protein function in vivo: A knockin mouse model demonstrates that the R49C mutation in alpha A-crystallin enhances protein insolubility and cell death. J Biol Chem. 283:5801-14.
  • Zhou, J., Leonard, M., Van Bockstaele, E.J., and Menko, A.S. 2007 Mechanism of Src kinase induction of cortical cataract following exposure to stress: destabilization of cell-cell junctions. Mol Vis. 2007 Jul 24;13:1298-310.
  • Walker, J.L., Wolff, I.M., Zhang, L., and Menko, A.S. 2007 Activation of Src kinases signals induction of posterior capsule opacification. Invest Ophthalmol Vis Sci. 48:2214-23.
  • Page, M.E., Oropeza, V.C, Sparks, S.E., Qian, Y., Menko, A.S., Van Bockstaele, E.J. 2007 Repeated cannabinoid administration increases indices of noradrenergic activity in rats. Pharmacol Biochem Behav. 86:162-168.
  • Weber, G.F. and Menko, A.S. 2006 Phosphatidylinositol 3-kinase is necessary for lens fiber cell differentiation and survival. Invest Ophthalmol Vis Sci. 47:4490-4499.
  • Weber G.F. and Menko A.S. 2006 Actin filament organization regulates the induction of lens cell differentiation and survival. Dev Biol. 295(2):714-29.
  • Weber G.F. and Menko A.S. 2005 The canonical intrinsic mitochondrial death pathway has a non-apoptotic role in signaling lens cell differentiation. J Biol Chem. 280:22135-45.
  • Weber G.F. and Menko A.S. 2005 Color image acquisition using a monochrome camera and standard fluorescence filter cubes. Biotechniques 38:52-56.
  • Zhou J. and Menko A.S. 2004 Coordinate signaling by Src and p38 kinases in the induction of cortical cataracts. Invest Ophthalmol Vis Sci. 45:2314-23.
  • Walker, J.L. and Menko, A.S. "Role of Matrix and Cell Adhesion Molecules in Lens Differentiation" in Development of the Ocular Lens, F.J. Lovicu and M.L. Robinson, eds., Cambridge University Press.
  • Menko, A.S. 2002 Lens epithelial cell differentiation, Exp. Eye Res. 75:485-490.
  • Walker, J.L., Zhang, L. and Menko, A.S. 2002 A signaling role for the uncleaved form of alpha6 integrin in differentiating lens fiber cells. Dev. Biol. 251:195-205.
  • Zhou, J. and Menko, A.S. 2002 Inhibition of Src family kinases blocks the formation of cortical cataracts in cultured chick embryo lenses. Invest. Ophthal. Vis. Sci. 43:2293-300.
  • Walker, J.L., Zhang, L. and Menko, A.S. 2002 The transition between proliferation and differentiation for lens epithelial cells is regulated by Src family kinases. Dev. Dyn. 224:361-372.
  • Menko, A.S., Zhang, L., Schiano, F. Kreidberg, J.A. and Kukuruzinska, M.A. 2002 Regulation of cadherin junctions during mouse submandibular development. Dev Dyn. 224:321-33.
  • Walker, J.L., Zhang, L., Woolkalis, M.J. and Menko, A.S. 2002 A role for alpha6 integrin during lens differentiation: Evidence for signaling through IGF-IR and ERK. Dev. Dyn. 223:273-284.
  • Van Bockstaele E.J., Menko A.S., Drolet G. 2001 Neuroadaptive responses in brainstem noradrenergic nuclei following chronic morphine exposure. Mol Neurobiol 23:155-171.
  • Kukuruzinska, M.A., Ryan, T., Kreidberg, J.A., Van Bockstaele, E. and Menko, A.S. 2001 Deficiency in alpha3beta1 integrin results in altered differentiation characteristics of the embryonic mouse submandibular gland. Dev. Dyn. 220:337-349.
  • Van Bockstaele, E.J., Peoples, J., Menko, A.S., McHugh, K. and Drolet, G. 2000 Decreases in endogenous opioid peptides in the rat medullo-coerulear pathway following chronic morphine treatment. J. Neuroscience 20:8659-8666.
  • Leong L, Menko AS, Grunwald GB. Differential expression of N- and B-cadherin during lens development. 2000 Investigative Ophthalmology and Visual Science. 41: 3503-10.
  • Ferreira-Cornwell MC, Veneziale RW, Grunwald GB, Menko AS. 2000 N-cadherin function is required for differentiation-dependent cytoskeletal reorganization in lens cells in vitro. Experimental Cell Research. 256: 237-47.

Last Updated by Jennifer Morris: Thursday, January 5, 2012 9:51:24 AM

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