Biomedical subjects

Murali D Bashyam

Publications and source records attributed to Murali D Bashyam.

5 recordsLinked to original sources

PubMed2005

Array-based comparative genomic hybridization identifies localized DNA amplifications and homozygous deletions in pancreatic cancer.

Pancreatic cancer, the fourth leading cause of cancer death in the United States, is frequently associated with the amplification and deletion of specific oncogenes and tumor-suppressor genes (TSGs), respectively. To identify such novel alterations and to discover the underlying genes, we performed comparative genomic hybridization on a set of 22 human pancreatic cancer cell lines, using cDNA microarrays measuring approximately 26,000 human genes (thereby providing an average mapping resolution of <60 kb). To define the subset of amplified and deleted genes with correspondingly altered expression, we also profiled mRNA levels in parallel using the same cDNA microarray platform. In total, we identified 14 high-level amplifications (38-4934 kb in size) and 15 homozygous deletions (46-725 kb). We discovered novel localized amplicons, suggesting previously unrecognized candidate oncogenes at 6p21, 7q21 (SMURF1, TRRAP), 11q22 (BIRC2, BIRC3), 12p12, 14q24 (TGFB3), 17q12, and 19q13. Likewise, we identified novel polymerase chain reaction-validated homozygous deletions indicating new candidate TSGs at 6q25, 8p23, 8p22 (TUSC3), 9q33 (TNC, TNFSF15), 10q22, 10q24 (CHUK), 11p15 (DKK3), 16q23, 18q23, 21q22 (PRDM15, ANKRD3), and Xp11. Our findings suggest candidate genes and pathways, which may contribute to the development or progression of pancreatic cancer.

Cell Line, Tumor↗

PubMed2004

The extracytoplasmic function sigma factors: role in bacterial pathogenesis.

Bacteria utilize a distinct subfamily of sigma factors to regulate extra cytoplasmic function (thus termed as ECF subfamily). Eubacteria appear to have evolved to incorporate extensive genetic diversity into their repertoire of ECF sigma factors (some species have more than 60 ECF sigma factors), while maintaining three major themes common to all members including: (1) they regulate and respond to extracytoplasmic functions; (2) they are themselves regulated by anti-sigma and/or anti-anti-sigma factors; and (3) most of them control a relatively small regulon. The cell wall is the first bacterial structure that comes in contact with the host during infection by pathogenic bacteria. The cell wall components are often associated with functions related to host cell invasion. It is therefore, likely that the ECF sigma factors regulate the bacterial response to host insult. Moreover, in some cases, virulence factors have been shown to be regulated directly by the ECF sigma factors. Unfortunately, this facet of the ECF sigma factors has not been an important area of study by researchers. The present review attempts to highlight the important role played by ECF sigma factors in bacterial pathogenesis and highlights several areas of future study involving the genetics of ECF sigma factors vis-à-vis bacterial pathogenesis.

Bacteria↗

PubMed2003

The homologous region sequence (hr1) of Autographa californica multinucleocapsid polyhedrosis virus can enhance transcription from non-baculoviral promoters in mammalian cells.

The Autographa californica multinucleocapsid polyhedrosis virus homologous region sequence hr1 enhances transcription from the viral polyhedrin promoter in Spodoptera frugiperda insect cells and independently functions as an origin of replication (ori) sequence. The binding of the host nuclear protein, hr1-binding protein (hr1-BP), is crucial for the enhancer activity (Habib, S., Pandey, S., Chatterji, U., Burma, S., Ahmad, R., Jain, A., and Hasnain, S. E. (1996) DNA Cell Biol. 15, 737-747 and Habib, S., and Hasnain, S. E. (1996) J. Biol. Chem. 271, 28250-28258). We demonstrate that hr1 can also enhance transcription from non-baculoviral promoters like cytomegalovirus and hsp70 in mammalian cells but does not support ori activity in these cells. Unlike insect cells, hr1 can also function in mammalian cells as an enhancer when present in trans. hr1 DNA sequence binds with high affinity and specificity to nuclear factors in the mammalian cells. The insect hr1-BP- and the hr1-BP-like proteins from mammalian cells (mhr1-BP) have different properties with respect to ion requirements, DNA groove binding, and molecular size. When mammalian cells are infected with a recombinant baculovirus containing two promoters, the baculovirus polyhedrin and Drosophila hsp70 gene promoter, the hsp70 gene promoter alone is active in these cells, and this activity is further enhanced by the presence of an additional hr1 in the recombinant virus. hr1 may thus also have a role in baculovirus-mediated gene delivery in mammalian cells.

Animals↗

PubMed2003

Molecular genetics of familial hypertrophic cardiomyopathy (FHC).

Familial hypertrophic cardiomyopathy is an autosomal dominant disease with a wide range of clinical features from benign to severe, and is the most common cause of sudden death in otherwise healthy individuals. The two prominent clinical features are left ventricular hypertrophy and myocyte/myofibrillar disarray. The former is responsible for clinical symptoms such as breathlessness and angina, whereas the latter may lead to sudden cardiac death. The last decade has seen an enormous improvement in our understanding of the molecular genetics of this disorder. The clinical heterogeneity has been linked to genetic heterogeneity; mutations in nine genes encoding sarcomere proteins have been shown to be the molecular basis for the disorder. However, attempts to establish a genotype-phenotype correlation for each of the more than 100 mutations that have been identified have not been highly successful. Additional genetic loci, as well as nongenetic factors such as lifestyle, sex, and age, have also been shown to play a role in modulating the clinical presentation of the disease. How each mutation results in hypertrophy and/or myofibrillar disarray is unclear. The present review discusses the current status of the molecular genetic characterization of this important disorder.

Cardiac Myosins↗

PubMed2002

Understanding cancer metastasis: an urgent need for using differential gene expression analysis.

Cancer is a multistep process and occurs as a result of the loss of control of cell division, leading to the initial tumor formation, which is followed by metastatic spread. Recent years have witnessed a vast improvement in the understanding of the molecular mechanisms regulating cell division and their links to tumorigenesis. The process of metastasis involves an intricate interplay between cell adhesion, proteolysis, migration, and angiogenesis. However, there is little knowledge of how these events are coordinately regulated in the tumor cell. Given that the uncontrolled spread of the tumor to distant organs is usually lethal, a study of the molecular mechanisms regulating metastasis assumes great significance. Recently, several technologies have been developed for analyzing differential gene expression. The current review discusses the importance of these technologies in the molecular analyses of metastasis.

Cell Adhesion↗