Animesh Ray, PhD

Animesh Ray
Areas of Expertise

Mechanisms of Disease, Neurobiology/Neuropharmacology, Systems, Computational, and/or Evolutionary Biology

Professor Ray, who joined KGI in July 2001, earned his PhD in microbial genetics from Monash University in Melbourne, Australia. His PhD research led to the identification of a gene for efficient plasmid maintenance in Escherichia coli and a method for generating a multi-copy infectious plasmid that is packageable inside a virus coat--an early example of synthetic biology. He subsequently conducted research at the Institute of Molecular Biology, University of Oregon, and the Department of Biology, Massachusetts Institute of Technology, during which periods he developed methods for precise in vivo chromosome engineering in yeast and in an experimental plant. He was an Assistant Professor from 1991 to 1995 and Associate Professor from 1996 to 2001 of Biology at the University of Rochester, New York, and an adjunct associate professor at the University of California, San Diego from 2001 to 2004.

Dr. Ray was a visiting professor at the University of Rochester from 2001 to 2004, at Institute for Systems Biology in Seattle in 2009, University of Hyderabad in 2009, and is currently a visiting faculty in California Institute of Technology, Pasadena. Research in his laboratory led to the discovery of the first known maternal effect embryo pattern formation gene in plants. His student, Teresa Golden, cloned a plant gene (DCL1) that later became known as the first member of the Dicer group of genes required for microRNA biogenesis. His PhD student Stephen Schauer identified the remaining known plant Dicer genes (DCL2-4). From 1999 to 2001, while on extended leave of absence from the University of Rochester, Dr. Ray directed research programs on regulation of gene expression and gene targeting at a plant biotechnology start-up company in San Diego.

His current research work involve systems biology of Huntington's disease, chromosome instability, non-coding RNAs in cancers, and cancer drug resistance mechanisms.

In the late 1990s, Dr. Ray, along with a computer scientist colleague Dr. Mitsunori Ogihara, published a series of papers on experimental and theoretical investigations on designing massively parallel computing devices using solution phase DNA chemistry. Accounts of this research were featured in several news media including the New York Times and the International Herald Tribune and he and Dr. Ogihara were featured in the book One Digital Day: How the Microchip is Changing Our World

He currently teaches courses on molecular systems biology that includes molecular mechanisms of human diseases and pharmacogenomics. He was KGI's faculty chair (2010-2016) and director of KGI's PhD program (2006-2016).

In his leisure, Ray is an avid amateur photographer, who has been profiled at a number of sites including in the Street Photography Magazine June 2018 issue.

See complete list of publications

Frumkin J.P., Patra B.N., Sevold A., Ganguly K., Patel C., Yoon S., Schmid M.B., and Ray A. The interplay between chromosome stability and cell cycle control explored through gene–gene interaction and computational simulation. Nucleic Acids Research doi: 10.1093/nar/gkw715 August 22 (2016)

Mazar J, Qi F, Lee B, Marchia J, Govindarajan S, Shelley J, Li JL, Ray A, Perera RJ. miR-211 functions as a metabolic switch in human melanoma cells. Mol. Cell. Biol., 36:1090 doi: 10.1128/MCB.00762-15 (2016)

An MC, O'Brien RN, Zhang N, Patra BN, De La Cruz M, Ray A, Ellerby LM. Polyglutamine disease modeling: epitope based screen for homologous recombination using CRISPR/Cas9 System. PloS Curr. doi: 10.1371/currents.hd.0242d2e7ad72225efa72f6964589369a. (2014)

Bhan, A. and Ray, A. A signature of power law network dynamics. BioRxiv doi: http://dx.doi.org/10.1101/004028 (2014)

Patra, B.N., Kon, Y., Yadav, G., Sevold, A., Frumkin, J.P., Vallabhajosyula, R.R., Hintze, A., Østman, B., Schosseau, J., Bhan, A., Marzolf, B., Tamashiro, J.K., Kaur, A., Baliga, N.S., Grayhack, E.J., Galas, D.J., Raval, A., Adami, C., Phizicky, E.M. & Ray, A. A genome wide dosage suppressor network reveals genetic robustness and a novel mechanism for Huntington's disease. BioRxiv doi: 10.1101/000265 (November 12, 2013)

J-L Li, J Mazar, C Zhong, GJ Faulkner, SS Subramaniam, S Govindarajan, Z Zhang, ME Dinger, G Meredith, C Adams, S Zhang, JS Mattick, Ray A, and RJ Perera. Genome-wide methylated CpG island profiles of melanoma cells reveal a melanoma coregulation network. Nature Sci. Report 3: 2962 (doi:10.1038/srep02962) (2013)

Perera, R. and Animesh Ray. Epigenetic Regulation of microRNA Genes and Their Role in Human Melanomas. Epigenomics 12: 81-90 (2012)

J Mazar, D Khaitan, D DeBlasio, SS Govindarajan, S Kopanathi, C Zhong, S Zhang, Ray A and RJ Perera The epigenetic regulation of microRNA genes and the role of miR-34b in cell invasion and motility in human melanomas. PloS ONE 6: e24922 (2011)

Kozhenkov S, Sedova M, Dubinina Y, Gupta A, Ray A, Ponomarenko J, Baitaluk M. "BiologicalNetworks - tools enabling the integration of multi-scale data for the host-pathogen studies". Bmc Systems Biology 2011 Jan 14;5:7 doi:10.1186/1752-0509-5-7

Mazar J, DeYoung K, Khaitan D, Meister E, Almodovar A, Goydos J, Ray A, Perera RJ. "The Regulation of miRNA-211 Expression and Its Role in Melanoma Cell Invasiveness". Plos One 2010;5(11):e13779

Vallabhajosyula RR, Chakravarti D, Lutfeali S, Ray A, Raval A. "Identifying Hubs in Protein Interaction Networks". Plos One 2009;4(4):e5344

Paladugu SR, Zhao S, Ray A, Raval A. "Mining protein networks for synthetic genetic interactions". Bmc Bioinformatics 2008;9(1):426

Langer M, Sniderhan LF, Grossniklaus U, Ray A. "Transposon Excision from an Atypical Site: A Mechanism of Evolution of Novel Transposable Elements". Plos One 2007;2(10):e965

Chickarmane V, Ray A, Sauro HM, Nadim A. "A model for p53 dynamics triggered by DNA damage". Siam Journal on Applied Dynamical Systems 2007;6(1):61-78

Baitaluk M, Sedova M, Ray A, Gupta A. "BiologicalNetworks: visualization and analysis tool for systems biology". Nucleic Acids Res. 2006 Jul 1;34(supp_2):W466-W471

Ray A. "Plant genetics - RNA cache genome trash?" Nature 2005 Sep 1;437(7055):E1-E2

Mlotshwa S, Schauer SE, Smith TH, Mallory AC, Herr JM, Roth B, Merchant DS, Ray A, Bowman LH, Vance VB. "Ectopic DICER-LIKE1 expression in P1/HC-Pro Arabidopsis rescues phenotypic anomalies but not defects in microRNA and silencing pathways". Plant Cell 2005 Nov;17(11):2873-2885

Book: Introduction to Biological Networks
Alpan raval and Animesh ray
04/2013; Publisher: Chapman & Hall/CRC Mathematical & Computational Biology, ISBN: 978-1584884637

Research Interests

Our laboratory is interested in exploring robustness of the genome. A variety of model systems and questions suitable for these model systems are being pursued.

Our work with yeast has led to the discovery of a network of many genes that can rewire cellular physiology to enable survival when one or more of approximately genes that essential for viability are mutated. This work demonstrated that eukaryotic genome has a previously unrecognized extent of evolutionary robustness, which has led to a novel approach to the discovery of genes that could impart drug resistance to lung cancer cells. Chromosome instability is a hallmark of cancer and identifying such genes in a model organism would allow for better assessment of human cancer cell functions. We have identified a number of genes as important for chromosome instability, and have innovated a computational method for studying their functions.

Our studies on genome robustness have indicated a role of DNA damage repair in neurodegenerative diseases. Large-scale genomic data were used to train a few of the latest machine learning algorithms, such as Random Forest and Gradient Boosting Machine, which led to the discovery that DNA damage repair is a crucial process in Huntington's disease—a genetically determined progressive degenerative disorder of the brain. Collaboration with colleagues using Drosophila melanogaster (Dr. Katerina Venderova's laboratory at KGI) and Caenorhabditis elegans (Dr. Paul Sternberg's laboratory at California Institute of Technology) are beginning to investigate this intriguing connection.

Over the past 11 years, we have been trying to understand the role of microRNAs (miRNAs) and long-noncoding RNAs (lncRNAs) as epigenetic agents of gene regulation in cancer, in collaboration with investigators in Sanford-Burnham-Prebys Institute for Cancer Research and Johns Hopkins University Medical Research Institute.

Most recently, in collaboration with biotech industry partners, we have innovated genome-wide gene-engineering for novel product development concepts and have engaged in vitro evolution to design a novel enzyme that does not exist in nature.

In the past, we had developed computational methods for predicting protein-protein interaction pairs, a method for analyzing complex interaction networks, discovered miRNA's role in the nucleus, and in collaboration with researchers at San Diego Supercomputer Center, designed a systems biology computational platform, and a mathematical model that simulates the dynamics of gene expression in certain cancer cells in response to DNA damage.

People

Past 10 years

  • Utkarsha Paithane (independent research student)
  • Henry Avetisian (independent research student)
  • Michael De La Cruz (PhD student)
    • Interest: Targeted genome modification and gene regulation, using TALENs and CRISPR/Cas enzymes; drug resistance development in cancer
  • Dr. Saumya Srivastava (Research Scientist)
    • Interest: In vitro evolution; gene targeting
  • Paola Hernandez (PhD student, graduated in 2018)
    • Interest: Computational approaches to understanding miRNA sequence variation in prostate cancer
  • Sonali Talele Lokhande (PhD student, graduated in 2017)
    • Interest: Computational biology; machine learning; Huntington's disease
  • Dr. Biranchi Patra (Senior Research Scientist, 2004-2013)
    • Interest: Genome robustness; synthetic biology
  • Jesse Frumkin (PhD student, graduated in 2012)
    • Interest: Genome instability; mathematical modeling of dynamical systems; cancer
  • Sri Paladugu (PhD student, jointly with Dr. Alpan Raval; graduated in 2011)
    • Interests: Machine learning; genomics
  • Dr. Ashis Bhan (Senior Research Scientist, 2008-2010)
    • Interests: Network analysis; graph theory

Resources

Webinar by Animesh Ray | April 4, 2018: An emerging role of DNA damage-repair in Huntington's disease

Lecture by Animesh Ray | January 19, 2017: The Impact of Society on Science

Recent publications from the Ray laboratory:

The long noncoding RNA SPRIGHTLY acts as an intranuclear organizing hub for pre-mRNA molecules

The interplay between chromosome stability and cell cycle control explored through gene–gene interaction and computational simulation

A genome wide dosage suppressor network reveals genomic robustness

A link between chromatin condensation mechanisms and Huntington's disease: connecting the dots

MicroRNA211 Functions as a Metabolic Switch in Human Melanoma Cells

Genome-wide methylated CpG island profiles of melanoma cells reveal a melanoma coregulation network

Polyglutamine Disease Modeling: Epitope Based Screen for Homologous Recombination using CRISPR/Cas9 System

1. Animesh Ray and Teresa Golden, “The gene encoding SHORT INTEGUMENTS1 of Arabidopsis thaliana and uses thereof” (Issued US Patent no. US6737561; May 18, 2004)

2. Ranjan Perera, Min Lu, and Animesh Ray, “Polynucleotide sequences from rice” (Issued US Patent no. US6544783; April 8, 2003)

3. Ranjan Perera, Min Lu, and Animesh Ray, “Polynucleotide sequences from rice” (Issued US Patent no. US7232940; June 19, 2007)