Microtubule Cytoskeleton and Centrosomes in Brain Cancer
Cancer research has been identified as a major priority at Drexel University College of Medicine. Our laboratory studies the pathobiology of pediatric tumors, with an emphasis on the centrosome and the microtubule-related mechanisms that go awry during cancerous cell proliferation. Our main focus has been on tumors of the central nervous system, especially those of glial origin (gliomas). We strive to achieve a dynamic interdisciplinary approach to translational research bridging basic science and pathology. Toward this goal, we have been eager to establish strong ties with the neuroscience community at the University. Presently, we collaborate with members of the Department of Neurobiology and Anatomy, utilizing state-of-the-art quantitative imaging techniques to study the expression of centrosome and relevant microtubule proteins as novel, clinically robust markers of malignant change in gliomas. Another principal goal of our laboratory is to make important strides toward linking immuno-morphological and functional observations with novel tumoricidal therapeutic strategies.
By way of background, I have a strong and longstanding interest in the alterations and modifiability of the microtubule cytoskeleton during neuronal and glial development and tumorigenesis. Currently, my research focuses on the expression, subcellular sorting and interaction of beta-tubulin isotypes, gamma-tubulin (the core structural protein of the pericentriolar material of centrosomes) and microtubule-severing proteins in human brain tumors and tumor cell lines. My translational diagnostic research interests are aimed at the characterization of new prognostic markers and the identification of molecular therapeutic targets for pediatric and adult-type gliomas. My studies involve primarily cellular and biochemical approaches that include cell culture, immunocytochemistry, immunofluorescence/confocal microscopy, immuno-electron microscopy, immunoblotting and immunoprecipitation, through collaborative interactions with Dr. Peter W. Baas and Dr. Jonathan Nissanov in the Department of Neurobiology and Anatomy, DUCOM, Dr. Pavel Draber in the Laboratory of the Biology of Cytoskeleton, Institute of Molecular Genetics, Academy of Sciences of the Czech Republic (Prague), and Dr. Moise Bendayan in the Department of Pathology and Cell Biology, University of Montreal.
Selected Publications
Katsetos CD, Del Valle L, Geddes JF, Assimakopoulou M, Legido A, Boyd JC, Balin BJ, Parikh NA, de Chadarevian J-P, Maraziotis T, Varakis JN, Matsas R, Spano A, Frankfurter A, Herman MM, Khalili K. Aberrant localization of the neuronal class III beta-tubulin in astrocytomas: A marker for anaplastic potential. Arch Pathol Lab Med 125:613-624, 2001 [ pdf ]
Katsetos CD, Del Valle L, Geddes JF, Aldape K, Boyd JC, Legido A, Khalili K, Perentes E, Mork SJ. Localization of neuronal class III beta?-tubulin in oligodendrogliomas. Comparison with Ki-67 proliferative index and 1p/19q status. J Neuropathol Exp Neurol 61:307-320, 2002
Katsetos CD, Herman MM, Mork SJ. Class III beta-tubulin in human development and cancer. Cell Motil Cytoskeleton 55:77-96, 2003
Katsetos CD, Legido A, Perentes E, Mork SJ. Class III beta-tubulin isotype: A key cytoskeletal protein at the crossroads of developmental neurobiology and tumor neuropathology. J Child Neurol 18:851-866, 2003
Katsetos CD, Reddy G, Draberova E, Smejkalova B, Del Valle L, Ashraf Q, Tadevosyan A, Yelin K, Maraziotis T, Mishra OP, Nissanov J, Mork S, Legido A, Baas PW, de Chadarevian J-P, Draber P. Altered cellular distribution and subcellular sorting of gamma-tubulin in astrocytic gliomas and human glioblastoma cell lines. J Neuropathol Exp Neurol 65:465-477, 2006 [ pdf ]
Katsetos CD, Draberova E, Smejkalova B, Reddy G, Bertrand L, de Chadarevian J-P, Legido A, Nissanov J, Baas PW, Draber P. Class III beta-tubulin and gamma-tubulin are co-expressed and form complexes in human glioblastoma cells. Neurochem Res 32:1387-1398, 2007
See my full list of publications in PubMed .
Neuronal Ontogeny and Phenotypic Characterization and Differentiation of Human Neuronal/Neuroblastic Tumors
Selected Publications
Katsetos CD, Liu HM, Zacks SI: Immunohistochemical and ultrastructural observations on Homer Wright (neuroblastic) rosettes and the "pale islands" of human cerebellar medulloblastomas. Hum Pathol 19:1219-1227, 1988
Katsetos CD, Herman MM, Frankfurter A, Gass P, Collins VP, Walker CC, Rosemberg S, Barnard RO, Rubinstein LJ. Cerebellar desmoplastic medulloblastomas: A further immunohistochemical characterization of the reticulin-free pale islands. Arch Pathol Lab Med 113:1019-1029, 1989
Katsetos CD, Herman MM, Frankfurter A, Uffer S, Perentes E, Rubinstein LJ. Neuron-associated class III beta-tubulin isotype, microtubule-associated protein 2 and synaptophysin in human retinoblastomas in situ: Further immunohistochemical observations on Flexner-Wintersteiner rosettes. Lab Invest 64:45-54, 1991
Katsetos CD, Frankfurter A, Christakos S, Mancall EL, Vlachos I, Urich H. Differential localization of class III beta-tubulin isotype (beta III) and calbindin-D 28k defines two neuronal types in the developing human cerebellar cortex. J Neuropathol Exp Neurol 52:655-666, 1993
Katsetos CD, Burger PC. Medulloblastoma. Sem Diagn Pathol 11:85-97, 1994
Katsetos CD, Karkavelas G, Frankfurter A, Vlachos I, Vogeley K, Schober R, Wechsler W, Urich H. The stromal Schwann cell during maturation of peripheral neuroblastomas: Immunohistochemical observations with antibodies to the neuronal class III beta-tubulin isotype (beta III) and S-100 protein. Clin Neuropathol 13:171-180, 1994
Vinores SA, Herman MM, Katsetos CD, May EE, Frankfurter A. Expression of neuron-associated class III beta-tubulin, tau and MAP2 in the D-283 Med cell line and in primary explants of human medulloblastomas. Histochem J 26:678-685, 1994
Katsetos CD, Krishna L, Frankfurter A, Karkavelas G, Wolfe D, Valsamis MP, Schiffer D, Vlachos I, Urich H. Cytomorphologic scheme of differentiating neuronal phenotypes in medulloblastomas based on immunolocalization of class III beta-tubulin and the proliferating cell nuclear antigen (PCNA)/cyclin. Clin Neuropathol 14:72-81, 1995
Katsetos CD, Herman MM, Krishna L, Vender J, Vinores SA, Agamanolis DP, Schiffer D, Burger PC, Urich H. Calbindin-D 28k in medulloblastoma subsets and in the human medulloblastoma cell line D283 Med. Arch Pathol Lab Med 119:735-743, 1995
Katsetos CD, Karkavelas G, Herman MM, Vinores SA, Provencio J, Spano AJ, Frankfurter A. Class III beta-tubulin isotype (beta III) in the adrenal medulla: I. Localization in the developing human adrenal medulla. Anat Rec 250:335-43, 1998
Karkavelas G, Katsetos CD, Geddes JF, Herman MM, Vinores SA, Cooper HS, Provencio J, Frankfurter A. Class III beta-tubulin isotype (beta III) in the adrenal medulla: II. Localization in primary human pheochromocytomas. Anat Rec 250:344-50, 1998
Katsetos CD, Herman MM, Balin BJ, Vinores SA, Hessler RB, Arking EJ, Karkavelas G, Frankfurter A. Class III beta-tubulin isotype (beta III) in the adrenal medulla: III. Differential expression of neuronal and glial antigens identifies two distinct populations of neuronal and glial-like (sustentacular) cells in the PC12 rat pheochromocytoma cell line maintained in a Gelfoam matrix system. Anat Rec 250:351-65, 1998
Katsetos CD, Del Valle L, Legido A, de Chadarevian J-P, Perentes E, Mork SJ. On the neuronal/neuroblastic nature of medulloblastomas: A tribute to Pio del Rio Hortega and Moises Polak. Acta Neuropathol (Berl) 105:1-13, 2003
Viral Neuro-oncogenesis
(in collaboration with Dr. Kamel Khalili, Temple University)
Selected Publications
Khalili K, Krynska B, Del Valle L, Katsetos CD, Croul S. Medulloblastomas and the human neurotropic polyomavirus, JC virus. Lancet 353:1152-1153, 1999
Krynska B, Del Valle L, Croul S, Gordon J, Katsetos CD, Carbone M, Giordano A, Khalili K. Detection of human neurotropic JC virus DNA sequence and expression of the viral oncogenic protein in pediatric medulloblastomas. Proc Natl Acad Sci USA 96:11519-11524, 1999
Del Valle L, Gordon J, Assimakopoulou M, Enam S, Geddes JF, Varakis JN, Katsetos CD, Croul S, Khalili K. Detection of JC virus DNA sequences and expression of the viral regulatory protein, T-antigen in tumors of the central nervous system. Cancer Res 6: 4287-4293, 2001
Del Valle L, Gordon J, Enam S, Delbue S, Croul S, Abraham S, Sujatha R, Assimakopoulou M, Katsetos CD, Khalili K. Detection of neurotropic polyomavirus JCV late gene product AGNO protein in human medulloblastomas. J Natl Cancer Inst 94:267-273, 2002
Del Valle L, Enam S, Lara C, Ortiz-Hidalgo C, Katsetos CD, Khalili K. Detection of JC Polyomavirus DNA sequences and cellular localization of T-Antigen and agnoprotein in oligodendrogliomas. Clin Cancer Res 8:3332-3340, 2002
Calcium and Nitric Oxide-Mediated Neuronal Damage During Brain Hypoxia-Ischemia
(in collaboration with Dr. Om P. Mishra, Dr. Agustin Legido and Dr. Maria Delivoria-Papadopoulos)
Selected Publications
Katsetos CD, Spandou E, Legido A, Taylor ML, Zanelli S, de Chadarevian J-P, Christakos S, Mishra OP, Delivoria-Papadopoulos M. Acute hypoxia-induced alterations of calbindin-D 28k immunoreactivity in cerebellar Purkinje cells of the guinea pig fetus at term. J Neuropathol Exp Neurol 60: 470-482, 2001
Parikh NA, Katsetos CD, Ashraf QM, Haider H, Legido A, Delivoria-Papadopoulos M, Mishra OP. Hypoxia-induced caspase-3 activation and DNA Fragmentation in cortical neurons of newborn piglets: Role of nitric oxide. Neurochem Res 28:1351-1357, 2003
Ashraf QM, Haider SH, Katsetos CD, Delivoria-Papadopoulos M, Mishra O. Nitric oxide-mediated alterations of protein tyrosine phosphatase activity and expression during hypoxia in the cerebral cortex of newborn piglets. Neurosci Lett. 362:108-112, 2004
Katsetos CD, Parikh NA, Fritz KI, Legido A, Delivoria-Papadopoulos M, Mishra OP. Effect of 7-nitroindazole sodium on the cellular distribution of neuronal nitric oxide synthase in the cerebral cortex of hypoxic newborn piglets. Neurochem Res 31:899-906, 2006
Calcium-Mediated Neuronal Damage in Epilepsy
(in collaboration with Dr. Agustin Legido)
Selected Publications
Valencia I, Mishra OP, Zubrow A, Fritz KI, Katsetos CD, Delivoria-Papadopoulos M, Legido A. The role played by calcium in neuronal injury following neonatal hypoxia or convulsions. Rev Neurol 42(Suppl3):S11-5, 2006
Valencia I, Mishra OP, Fritz K, Zubrow A, Katsetos CD, Delivoria-Papadopoulos M, Legido A. Increased nuclear calcium influx in neonatal seizures. Neurochem Res 31:1231-1237, 2006
Valencia I, Legido A, Yelin K, Khurana D, Kothare SV, Faerber E, Katsetos CD. Anomalous inhibitory circuits in cortical tubers of human tuberous sclerosis associated with refractory epilepsy: Aberrant expression of parvalbumin and calbindin-D 28k in dysplastic cortex. J Child Neurol 21:1058-1063, 2006
Pediatric CNS Demyelinating Diseases and Experimental Models of Multiple Sclerosis
(in collaboration with Dr. Emilia Oleszak and Dr. Chris D. Platsoucas, Temple University)
Selected Publications
Oleszak EL, Katsetos CD, Kuzmak J, Varadhachary A. Inducible nitric oxide synthase in Theiler's murine encephalomyelitis virus-infected mice. J Virol 71:3228-3235, 1997
Oleszak EL, Zaczynska E, Battacharjee M, Butonoi C, Legido A, Katsetos CD. Presence of inducible nitric oxide synthase and nitrotyrosine in subpopulations of monocytes/macrophages and astrocytes of acute, but not chronic multiple sclerosis. Clin Diagn Lab Immunol 5:438-445, 1998
Chang JR, Zaczynska E, Katsetos CD, Platsoucas CD, Oleszak EL. Differential expression of TGF-?, IL-2 and other cytokines in the CNS of Theiler's murine encephalomyelitis virus-infected susceptible and resistant strains of mice. Virology 278:346-360, 2000
Oleszak E, Lin WL, Legido A, Melvin J, Hardison H, Katsetos CD, Platsoucas CD. Vbeta? chain T cell receptor transcripts are clonally expanded in the cerebrospinal fluid of a child with recurrent disseminated encephalomyelitis following hepatitis A infection. Clin Diagn Lab Immunol 8:984-992, 2001
Oleszak EL, Hoffman BE, Chang JR, Zaczynska E, Katsetos CD, Platsoucas CD, Harvey N. Apoptosis of infiltrating T cells in the central nervous system of mice infected with Theiler's murine encephalomyelitis virus (TMEV). Virology 315:110-123, 2003
Oleszak E, Chang JR, Friedman HS, Katsetos CD, Platsoucas CD. Theiler's encephalomyelitis as a model of multiple sclerosis. Clin Microbiol Rev 17:174-207, 2004
Oleszak, Katsetos CD, Kuzmak J, Varadhachary A, iNOS in TMEV infection. In: Lavi E, Constantinescu CS, (Eds.) Experimental Models of Multiple Sclerosis, Springer (Neuroscience Division), New York, 2005, XII [ISBN: 0-387-25517-6]
Legido A, Tenenbaum SN, Katsetos CD, Menkes JH. Autoimmune and postinfectious diseases. In: Menkes JH, Sarnat HB, Editors, Child Neurology, Lippincott-Williams & Wilkins, Philadelphia/Baltimore, 2005, pp 557-657 [ISBN: 0-7817-5104-7]
Pediatric Neuropathology
(in collaboration with Dr. Jean-Pierre de Chadarevian and Dr. Agustin Legido)
Selected Publications
Katsetos CD, Krishna L. Lobar pilocytic astrocytomas of the cerebral hemispheres: I. Diagnosis and nosology. Clin Neuropathol 13:295-305, 1994
Katsetos CD, Krishna L, Friedberg E, Reidy J, Karkavelas G, Savory J. Lobar pilocytic astrocytomas of the cerebral hemispheres. II. Pathobiology - Morphogenesis of the eosinophilic granular bodies of pilocytic astrocytomas. Clin Neuropathol 13:306-314, 1994
Katsetos CD, Fincke JE, Legido A, Lischner HW, de Chadarevian J-P, Kaye EM, Platsoucas CD, Oleszak EL. Angiocentric CD3+ T-cell infiltrates in HIV-1-associated central nervous system disease in children. Clin Diagn Lab Immunol 6:105-114, 1999
Bakaeen G, Winkler S, Bakaeen L, Rehani LA, Katsetos CD. Congenital macroglossal angiodysplasia. Arch Pathol Lab Med 124:1349-1351, 2000
de Chadarevian J-P, Legido A, Miles DK, Katsetos CD. Epilepsy, atherosclerosis, myocardial infarction, and carbamazepine. J Child Neurol 18:150-1, 2003
Pascual-Castroviejo I, Pascual-Pascual SI, Gutierrez-Molina M, Urich H, Katsetos CD. Cerebellar hypoplasia with heterotopic Purkinje cells in the molecular layer and preservation of the granule layers associated with severe encephalopathy. A new entity? Neuropediatrics 34:160-164, 2003
de Chadarevian J-P, Pascasio JM, Campbell A, Katz D, Halligan H, Katsetos CD. Malignant peripheral nerve sheath tumor arising from a ganglioneuroma in a 6-year-old boy. Pediatr Dev Pathol 7:277-84, 2004
Legido A, Valencia I, Katsetos CD. Cerebrovascular disorders in prerterm neonates. Rev Neurol 42(Suppl3):S23-38, 2006
de Chadarevian J-P, Halligan G , Reddy G, Bertrand L, Pascasio JM, Faerber E, Katsetos CD. Glioneuronal phenotype in a diencephalic pilomyxoid astrocytoma. Pediatr Dev Pathol 9:480-487, 2006
Neuropathology of Schizophrenia
Katsetos CD, Hyde TM, Herman MM. Neuropathology of the cerebellum in schizophrenia - an update: 1996 and future directions. Biol Psychiatry. 42:213-224, 1997
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