Cellular and Structural Biology | Faculty
Department of Cellular & Structural Biology

CSB Faculty

 

Photo of Dr. Pereira-Smith Olivia Pereira-Smith, Ph.D.
Professor

 

Worcester Polytechnic Institute, 1981

 

STCBM (210) 562-5069
SMITHO@UTHSCSA.EDU

 

Departments of Cellular and Structural Biology, and Sam and Ann Barshop Institute for Longevity and Aging Studies Ph.D., Worcester Polytechnic Institute Postdoctoral, W. Alton Jones Cell Science Center.

 

Research Interests:
The limited division of normal cells in culture is proposed as a model for cell aging. To understand the molecular and genetic basis for this loss of cell division in normal cells, we have chosen to study abnormal human cells (tumor derived, virus transformed) that have escaped from senescence and proliferate indefinitely (immortal). We have found that hybrids from fusion of various immortal cells with normal cells regain the senescent phenotype. This indicates that the phenotype of immortality is the result of recessive changes in genes regulating growth. We then fused various immortal human cells with each other. If the cell lines had immortalized through the same changes, immortal hybrids would be obtained. If different events had led to immortalization, hybrids would have limited division since the recessive (defective) genes of each cell line would be complemented by the good genes present in the other.

 

By this analysis we have identified four complementation groups for indefinite division. Using microcell fusion we determined that a normal human chromosome 4 can suppress the immortal phenotype in immortal cells lines assigned to group B. We then cloned the gene MORF4 as the cause of this effect. It is a member of a family of genes that are involved in chromatin remodeling and transcriptional regulation.

 

The MORF related genes, MRG15 and MRGX encode proteins that are present in multiple nucleoprotein complexes and the composition of other proteins in these complexes determines whether a gene promoter is activated or repressed. MRG15 has been identified in the Tip60/NuA4 complex in yeast, Drosophila and human cells. This has been implicated in cell cycle, apoptosis and DNA repair. MRG15 is critical for survival of Drosophila and mice and nulls are embryonic lethal. Future studies aim to identify gene targets of these complexes, the changes that occur as cells become senescent and the role of MORF4.

 

We are also involved in collaborative studies on telomeres and telomerase with Drs. I Rubelj, V Gorbunova and A Seluanov, and on mortalin with Drs R Wadhwa and S Kaul.

 

Research Techniques:
Cell culture of normal and immortal human and mouse cells, use of genetically modified mice, immunostaining and histochemistry, molecular and biochemical techniques: Southern, northern, western, immunoprecipitation, chromatin immunoprecipitation, PCR, real time PCR, plasmid constructs, adenoviral constructs.

 

PUBLICATIONS:
Garcia SN, Kirtane BM, Podlutsky AJ, Pereira-Smith OM, Tominaga K. (2007) Mrg15 null and heterozygous mouse embryonic fibroblasts exhibit DNA-repair defects post exposure to gamma ionizing radiation. FEBS Lett. 2007 Nov 13;581(27):5275-81. Epub 2007 Oct 18.

 

Jackson JG, Pereira-Smith OM. (2006) p53 Is Preferentially Recruited to the Promoters of Growth Arrest Genes p21 and GADD45 during Replicative Senescence of Normal Human Fibroblasts. Cancer Res. Sep 1;66(17):8356-60.

 

Wadhwa R, Takano S, Kaur K, Deocaris CC, Pereira-Smith OM, Reddel RR, Kaul SC. (2006) Upregulation of mortalin/mthsp70/Grp75 contributes to human carcinogenesis.Int J Cancer. 2006 Jun 15;118(12):2973-80.

 

Jackson JG, Pereira-Smith OM. (2006) Primary and compensatory roles for RB family members at cell cycle gene promoters that are deacetylated and downregulated in doxorubicin-induced senescence of breast cancer cells. Mol Cell Biol. 2006 Apr;26(7):2501-10.

 

Bowman BR, Moure CM, Kirtane BM, Welschhans RL, Tominaga K, Pereira-Smith OM, Quiocho FA. (2006) Multipurpose MRG domain involved in cell senescence and proliferation exhibits structural homology to a DNA-interacting domain.Structure. 2006 Jan;14(1):151-8.

 

Tominaga K, Kirtane B, Jackson JG, Ikeno Y, Ikeda T, Hawks C, Smith JR, Matzuk MM, Pereira-Smith OM (2005) MRG15 regulates embryonic development and cell proliferation. Mol Cell Biol.;25(8):2924-37.