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|Ivana de la Serna, Ph.D.
Biochemistry and Cancer Biology
In eukaryotes, DNA is packaged into chromatin, the basic unit of which is the nucleosome. Chromatin structure plays a critical role in the regulation of gene expression by imposing topological constraints and by creating a barrier for transcriptional regulators. SWI/SNF enzymes are multiprotein complexes that alter chromatin structure in an ATP dependent manner and are involved in the regulation of gene expression. Components of the SWI/SNF complex are essential for mouse development and play important roles in several human cancers.
Cellular differentiation is characterized by the activation of previously silent genes embedded in repressive chromatin structure that is inaccessible to the transcriptional machinery. SWI/SNF enzymes interact with master regulators of differentiation to disrupt chromatin structure and activate lineage specific gene expression. We have previously determined that SWI/SNF enzymes interact with the master regulator of melanocyte differentiation, Microphthalmia Transcription Factor (MITF). MITF regulates the expression of genes that encode the enzymes needed for melanin synthesis, melanosome structure, and melanocyte survival. The main focus of my research is to study the functional role of SWI/SNF enzymes in the regulation of gene expression during melanocyte differentiation and to determine how SWI/SNF function is de-regulated in melanoma.
Member of the mentoring faculty for the Biomedical Sciences Graduate Program (Cancer Biology Track).
Ph.D. 1998 University of California, Davis, Davis, CA
B.S. 1984 Cornell University, Ithaca, NY
RECENT ACADEMIC APPOINTMENTS:
2012-pres Associate Professor, Biochemistry & Cancer Biology, University of Toledo Health Scicence Campus
2005-2012 Assistant Professor, Biochemistry & Cancer Biology, University of Toledo Health Science Campus
2004-2005 Research Assistant Professor, Department of Cell Biology, University of Massachusetts Medical School
1998-2004 Postdoctoral Fellow, Department of Cell Biology, University of Massachusetts Medical School,
1990-1997 Research & Teaching Assistant, Department of Plant Pathology, Univesity of California, Davis
1988-1990 Research & Teaching Assistant, Department of Biological Sciences, California State University, Fullerton
Mehrotra, A., Saladi, S.V., Trivedi, A., Aras, S., Qi, H., Jayanthi, A., Setaluri, V., and de la Serna, I.L. (2014) Modulation of BRAHMA expression by the mitogen-activated protein kinase/extracellular signal regulated kinase pathway is associated with changes in melanoma proliferation. Arch. Biochem. Biphys. (accepted).
Mehrotra, A., Mehta, G., Aras, S. Trivedi, A., and de la Serna, I.L. (2014) SWI/SNF Chromatin remodeling enzymes in melanocyte differentiation and melanoma. Crit. Rev. Eukaryot. Gene Expr. 24:151-161.
Mehrotra, A., Joe, B., and de la Serna, I.L. (2013) SWI/SNF chromatin remodeling enzyme are associated with cardiac hypertrophy in a genetic rat model of hypertension. J. Cell Physiol. 228:2337-2334.
Marathe, H.G., Mehta, G., Zhang, X., Datar, I., Mehrotra, A. Yeung, K.C., and de la Serna, I.L. SWI/SNF enzymes promote SOX10-mediated activation of meyline gene expression. PLoS One 16:e69037.
Saladi, S.V., Wong, P.G., Trivedi, A.R., Marathe, H.G., Keenen, B., Aras, S., Liew, Z.Q., Setaluri, V., and de la Serna, I.L. (2013) BRG1 promotes melanoma survival in UV-irradiated melanoma cells by cooperating with MITF to activate the melanoma inhibotor of apoptosis gene. Pigment Cell Melanoma Res. 26:377-391.
Ren, G., Feng, J., Datar, I.,Yeung, A.H., Saladi, S.V.,Feng, Y., de la Serna, I., and Yeung, K.C. (2012) A micro-RNA connection in BRaf(V600E)-mediated premature senescence of human melanocytes. Int. J. Cell Biol. 2012:913242.
Keenen, B., Qui, H., Saladi, S.V., Yeung, M., and de la Serna, I.L. (2010) Heterogeneous SWI/SNF complexes promote expression of MITF-target genes in melanoma. Oncogene 29:81-92.
Keenen, B., de la Serna, IL (2009) Chromatin remodeling in embryonic stem cells: regulating the balance between pluripotency and differentiation. J. Cell Phys. 219:1-7.
de la Serna, I., Ohkawa, Y., Imbalzano, A.N. (2006) Chromatin remodelling in mammalian differentiation: lessons from ATP-dependent remodellers. Nat. Rev. Genet. 7:461-473.
de la Serna, I., Ohkawa, Y., Higashi, C., Dutta, C., Osias, J., Kommajosyula, N., Tachibana, T., Imbalzano, A.N. (2006) The microphthalmia-associated transcription factor requires SWI/SNF enzymes to activate melanocyte-specific genes. J. Biol. Chem. 281:20233-20241.
de la Serna, I., Ohkawa, Y., Berkes, C.A., Bergstrom, DA, Dacwag, C.S., Tapscott, S.J., Imbalzano, A.N. (2005) MyoD targets chromatin remodeling complexes to the myogenin locus prior to forming a stable DNA-bound complex. Molec. Cell. Biol. 25:3997-4009.
Hill DA, de la Serna I., Veal T., and Imbalzano A.N. (2004) BRCA1 interacts with dominant negative SWI/SNF enzymes without affecting homologous recombination or radiation-induced gene activation of p21 or Mdm2. J. Cell Biochem. 91:987-998.
Moen, PT, CV Johnson, M Byron, L Shopland, I de la Serna, AN Imbalzano, and JB Lawrence. (2004) Cell-type specific organization of gene loci during skeletal myogenesis: Two muscle-specific genes re-position to the periphery of SC-35 domains upon differentiation. Mol Biol of the Cell. 15:197-206.
de la Serna I., and Imbalzano A.N. (2002) Unfolding heterochromatin for replication. Nature Genet. 32:560-562 (News and Views article).
Roy K., de la Serna I., and Imbalzano A.N. (2002) The Myogenic Basic Helix-Loop-Helix Family of Transcription Factors Show Similar Requirements for SWI/SNF Chromatin Remodeling Enzymes during Muscle Differentiation in Culture. J Biol Chem. 277:33818-33824.
de la Serna I., Roy K., Carlson K.A., and Imbalzano A.N. (2001) MyoD can induce cell cycle arrest but not muscle differentiation in the presence of mutant SWI/SNF chromatin remodeling enzymes. J Biol Chem. 276:41486-41491.
de la Serna I., Carlson K.A., and Imbalzano A.N. (2001) Mammalian SWI/SNF complexes promote MyoD-mediated muscle differentiation. Nature Genet. 27:187-190.
de la Serna I., Carlson K.A., Hill D.A., Guidi C.J., Stephenson R.O., Said S., Kingston R.E., and Imbalzano A.N. (2000) Mammalian SWI/SNF complexes contribute to activation of the hsp70 gene. Mol Cell Biol. 20:2839-2851.