Mazar, J.; DeYoung, K.; Meister, E.; Almodovar, A.; Goydos, J.; Ray, A.; Perera, R.J.  "miR-211 targets the Potassium channel transcript KCNMA1 and inhibits the growth and invasion of human melanoma cells" (submitted)

Vallabhajosyula, R.R.; Chakravarti, D.; Lutfeali, S.; Ray, A.; Raval, A. "Identifying hubs in protein interaction networks" PLoS ONE 4: e5344 (2009)

Paladugu, S.R.; Zhao, S.; Ray, A.; Raval, A. "Mining protein networks for synthetic genetic interactions" BMC Bioinformatics 9: 426 (2008)

Langer, M.; Snyderhan, L.F.; Grossniklaus, U.; Ray, A. "Transposon excision from an atypical site: A mechanism of evolution of novel transposable elements" PLoS One 2: e965 (2007)

Perera, R.J.; Ray, A. "MicroRNAs in the search for understanding human diseases" J. BioDrugs 21: 97-104 (2007)

Chickarmane, V.; Ray, A.; Sauro, H.; Nadim, A. "A model for p53 dynamics triggered by DNA damage" SIAM J. Applied Dynamical Systems 6: 61-78 (2007)

Baitaluk, M.; Sedova, M.; Ray, A.; Gupta, A. "BiologicalNetworks: visualization and analysis tool for systems biology" Nucleic Acids Res. 34: 466-471 (2006)

* Perera, R.J.; Marcusson, E.G.; Koo, S.; Kang, X.; Kim, Y.; White, N.; Dean, N.M. "Identification of novel PPARgamma target genes in primary human adipocytes" Gene 369: 90-99 (2006)
*Work partially carried out in the Ray laboratory

Baitaluk, M.; Quian, X.; Godbole, S.; Raval, A.; Ray, A.; Gupta, A. "PathSys: Integrating molecular interaction graphs for systems biology" BMC Bioinformatics 7: 55 (2006)

Ray, A. "RNA cache or genome trash?" Nature 434: 505-509 (2005)

Mlotswa, S.; Schauer, S.E.; Smith, T.H; Mallory, A.; Herr,  J.M.; Roth,  B.; Merchant, D.; Ray,  A.; Bowman, L.H.; Vance, V.H. "Ectopic DICER-LIKE1 expression in P1/HC-Pro Arabidopsis rescues phenotypic anomalies but not defects in microRNA and silencing pathways" Plant Cell 17: 2873-2855 (2005)

Gupta, N.; Law, A.; Poddar, R.; Louie, M.; Ray, A.; Chakravarti, D.N. "Toxicoproteomics: Applications in drug development" Current Proteomics 2: 97-102 (2005)

Law, A.; Gupta, N.; Louie, M.; Poddar, R.; Ray, A.; Chakravarti, D.N. "Identification and characterization of plant allergens using proteomic approaches" Current Proteomics 2: 147-164 (2005)

Ray, A. "Displaced T-loop models and telomere maintenance in plants" Nature Reviews Genetics (2004)

Papp, I.; Mette, M.F.; Aufsatz, W.; Daxinger, L.; Schauer, S.S.; Ray, A.; van der Winden, J.; Matzke, M.; Matzke, A.J.M. "Evidence for Nuclear Processing of Plant miRNA and 21-22 nt siRNA Precursors" Plant Physiol. 132: 1382-1390 (2003)

Gupta, A.; Yang, Y.;  Bagchi, A.; Ray, A. "Declarative specification of gene regulatory networks and query evaluation in PathSys" In  Proc. 19^th International Conference on Data Engineering (2003)

Schauer, S. E.; Jacobsen, S.E.; Meinke, D.W; Ray, A. "DICER-LIKE1: Blind men and elephants in Arabidopsis   development" Trends in Plant Sci. 7: 487-491 (2002)

Golden, T.; Schauer, S.E.; Lang, J.D; Pien, S.; Mushegian, A.; Grossniklaus, U.; Meinke, D.; Ray, A. "SHORT INTEGUMENTS1 / SUSPENSOR1 / CARPEL FACTORY, a Dicer homologue, is a maternal-effect gene required for embryo development in Arabidopsis" Plant Physiol. 130: 808-822 (2002)

Ray, A; Langer, M. "Homologous recombination: ends as the means" Trends in Plant Sci. 7: 435-440 (2002)

Ogihara M.; Ray, A. "The minimum-model DNA computation on a sequence of probe arrays" In   Proceedings of the 3^rd International Conference on Unconventional Models of Computation, UMC 200, Kobe (2002)

Calude, C.; Dinneen, M.J.; Peper, F.(Eds.) Published in Lecture Notes in Computer Science vol. 2509: 38-49, Springer Verlag (Heidelberg)

Ogihara, M.; Ray, A. "DNA Computing on a Chip" Nature 403: 143-145 (2000)

Understanding the Basis of Robustness of Gene Regulatory Networks

It has been argued that biological interaction networks are robust to many kinds of perturbations.  The evolutionary mechanisms of such robustness properties are not easy to appreciate.  For example, one mechanism of robustness (one that is incorporated by systems engineers) is redundancy.  However, since evolution is thought to act upon the function of single genes, it is unclear how redundancy can be stable over evolution since there should be no selection pressure acting upon purely redundant functional units.  To answer such questions Professor Ray's laboratory, in collaboration with colleagues at the University of Rochester Medical School and the University of Toronto, are mutating each essential gene of Saccharomyces cerevisiae.  They then select for all possible genes in the genome which, if over-expressed, could potentially suppress the lethal effects of the original mutation.  The idea is that each essential gene if mutated leaves 'holes' in the network of genes and proteins, but by over-expressing the communication traffic through other pathways, 'shunt pathways' could potentially be revealed that make life possible even in the presence of these lethal 'holes'.  If a dense network of 'holes' and 'shunt pathways' can be obtained, the rules that underlie the readjustment of communication networks under conditions of potentially lethal perturbations can be studied.  These studies have the potential to reduce the deleterious effects of drugs on normal cells while maximizing the lethal effects of the same drugs on diseased cells.

Analysis of Networks that Regulate Complex Developmental Pathways

Simple developmental decisions, such as sporulation in yeast triggered by a change in the food quality or the differentiation of a stem cell upon receiving a morphogen signal, appear to involve differential regulation of hundreds of genes.  Reverse engineering of the network of regulation among these hundreds of genes and their products requires a combination of diverse genomic scale experimental techniques and mathematical modeling.  Professor Ray's laboratory is investigating sporulation in yeast as one such model system.  Using microarray profiling of thousands of mRNAs and mathematical analysis normally used in signal processing in electrical engineering, they are probing the networks of genes and proteins, and their modification states, which underlie these dynamical properties of gene expression.  These studies will ultimately help provide better understanding of the workings of normal and pathological human cells, and should enable insights for therapeutic intervention.

Epigenetic Processes 

Although cells respond to environmental stimuli in many different ways, it is likely, nonetheless, that there are conserved themes in these processes.  One aim of Professor Ray's laboratory is to understand how exposures to different nutritional conditions alter the profile of epigenetic signatures (proteins and their modification states that bind to DNA) acting upon the genome in yeast.  Using genome wide chromatin immunoprecipitation techniques (ChIP-Chip), the lab is investigating the histone code associated with different chromosomal regions under different metabolic conditions.  A further project in Professor Ray's laboratory investigates the epigenetic signatures associated with chromosome break repair and genetic recombination.  Since it is increasingly apparent that many complex human diseases, such as most cancers (many of which involve faulty DNA damage repair), diabetes, obesity and numerous degenerative diseases, are due to abnormal epigenetic processes, understanding the epigenetic mechanisms behind adaptation to nutritional conditions and DNA damage could provide insights into human diseases as well.  Professor Ray and his collaborator, Dr. Ranjan Perera, are also extending the analysis of epigenetic signatures to the study of melanoma with the goal of identifying specific biomarkers for this malignant condition.

1. Animesh Ray and Teresa Golden, “The gene encoding SHORT INTEGUMENTS1 of Arabidopsis thaliana and uses thereof” (Issued US Patent no. US6737561)

2. Ranjan Perera, Min Lu, and Animesh Ray, “Polynucleotide sequences from rice” (Issued US Patent no. US6544783)