Raga Krishnakumar

Senior Member of the Technical Staff

Author profile picture

Senior Member of the Technical Staff

rkrishn@sandia.gov

(925) 294-3292

Sandia National Laboratories, California
 P.O. Box 969
 Livermore, CA 94551-0969

Biography

Raga Krishnakumar’s main area of research is detecting, understanding and regulating mammalian cell fate, including fate changes with response to environmental stimuli such as infectious agents or stress conditions. Specifically, she is interested in how we can generate and deploy therapeutic cells for a variety of disease states and conditions that are pertinent both to national security and public health. She applies an integrated approach of high-throughput experimentation, data analytics and functional assays to identify mechanisms by which to generate context-specific therapeutic cells. In addition, she is involved in a number of projects at Sandia as a computational biologist, including the identification and classification of mobile elements in bacterial genomes, and real-time selective sequencing of specific nucleic acids in mixed samples using the Oxford Nanopore MinION long-read sequencer.

Education

Bachelor’s Degree: Bachelor of Arts (honors) in Natural Sciences (Biochemistry), University of Cambridge, UK (2001 – 2004)

Doctoral Degree: : Ph.D. in Biochemistry, Cell and Molecular Biology, Cornell University (2004 – 2010); PI: W. Lee Kraus

Postdoctoral Fellowships:

  • Postdoctoral Fellow, Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco (2010 – 2016); PI: Robert Blelloch
  • Postdoctoral Appointee, Systems Biology Department, Sandia National Laboratories (2016); PIs: Michael Bartsch and Kelly Williams).

Raga Krishnakumar did her undergraduate studies at the University of Cambridge, UK. She majored in Natural Sciences with a specialization in Biochemistry. She then did her Ph.D. work with Dr. Lee Kraus at Cornell University in Ithaca, NY, where she focused on the role of two nucleosome-binding proteins – Poly ADP-ribose polymerase-1 (PARP-1) and histone H1 – in the regulation of chromatin structure and transcription in breast cancer cells and cardiomyocytes. Her work was funded in part by an American Heart Association predoctoral fellowship. She completed her Ph.D. in 2010.

Following this, Krishnakumar did her postdoctoral work at the University of California San Francisco (UCSF) in the laboratory of Dr. Robert Blelloch. She led two main projects during her postdoc. First, in collaboration with a graduate student in the lab, she found that microRNA activity is suppressed in mature oocytes due to limiting amounts of the effector Argonaute protein. The second project focused on the epigenetic regulation of mouse embryonic stem (ES) cell differentiation, specifically showing that a transcription factor, Foxd3, that is central to regulating the timing of differentiation through enhancer priming. In addition, during her postdoc, Krishnakumar trained as a computational biologist and bioinformatician, and acquired both the coding and statistics knowledge required to perform in-depth analysis of large data sets. Her postdoctoral work was funded in part by an A.P. Giannini postdoctoral fellowship.

Research Interests

Engineering Therapeutic Mesenchymal Stem Cells

Krishnakumar’s goal is to harness the incredible versatility of mesenchymal stem cells (MSCs) as antibacterial, immunomodulatory and regenerative cells for therapeutic purposes, with a special focus on bacterial infection in mammalian systems. Krishnakumar and her team are characterizing the molecular signatures (transcriptomic, epigenomic and proteomic) that correlate with functional outcomes in order to a) be able to successfully isolate properly therapeutic MSCs and b) convert other cell types into stably therapeutic MSCs. They are generating computational models using our large omic data sets combined with readouts on functional outcomes that inform them on how specific cells will behave based on their molecular profile, and how they can customize the behavior of these cells by targeting specific genomic regions and pathways.

Identifying and Classifying Bacterial Mobile Genomic Elements

Understanding the mechanisms underlying the trajectories of bacterial mobile elements is of crucial importance, since bacteria use these elements to acquire drug-resistance and toxicity genes. In collaboration with Kelly Williams, Krishnakumar has worked on the classification of bacterial mobile elements identified by two pieces of software developed at Sandia – Islander and Comparator. Specifically, she is interested in understanding how mobile elements differ from their host genomes in terms of composition and size and has used this information to generate a model that identifies false positive elements. Her work focuses specifically on genomic islands, which are characteristically modular in their nature (they have groups of genes that travel and function together). She has therefore developed a clustering protocol to group islands elements based on a range of similarity, from near-identical to islands that share some modules but have evolved divergently for some time.

Real-time Selective Sequencing Using the MinION Nanopore Sequencer

Given the short timelines often associated with pathogenesis in infectious disease, rapid identification and diagnosis of agents is critical for successful treatment of affected patients, and the prevention of spreading, both within single individuals and throughout the population at large. In an effort to address this, in collaboration with Michael Bartsch, she has characterized the performance of the long-read nanopore sequencer from Oxford Nanopore Technologies, the MinION, across genomes with a range of nucleotide bias. She examined the likelihood of both stochastic and deterministic errors as a result of the evolving hardware and base calling software. Her team is also one of the few groups worldwide making us of the ability of the MinION to perform interactive sequencing (i.e. real-time decision making on whether to sequence a particular strand based on the pattern of the leading segment). They have established a program that performs real-time thresholding and basecalling, and decides which strands of nucleic acid to prioritize for sequencing, allowing them to relatively enrich a specific region of interest over background. Through collaborations, they are currently looking at potential real-world applications for this technology. 

Publications

Michael Smith, Armida Carbajal, Eva Domschot, Nicholas Johnson, Akul Goyal, Christopher Lamb, Joseph Lubars, William Kegelmeyer, Raga Krishnakumar, Sophie Quynn, Ramyaa Ramyaa, Stephen Verzi, Xin Zhou, (2022). MalGen: Malware Generation with Specific Behaviors to Improve Machine Learning-based Detectors https://doi.org/10.2172/1893244 Publication ID: 80379

Raga Krishnakumar, Kurt Sjoberg, Andrew Fisher, Gloria Doudoukjian, Elizabeth Webster, (2022). Combined Imaging and RNA-Seq on a Microfluidic Platform for Viral Infection Studies https://doi.org/10.2172/1888155 Publication ID: 80227

Donald Robinson, Michael Foster, Christopher Bennett, Austin Bhandarkar, Elliot Fuller, Vitalie Stavila, Dan Spataru, Raga Krishnakumar, Neil Cole-Filipiak, Paul Schrader, Krupa Ramasesha, Mark Allendorf, Albert Talin, (2022). Proton Tunable Analog Transistor for Low Power Computing https://doi.org/10.2172/1889340 Publication ID: 80273

Stephen Verzi, Raga Krishnakumar, Drew Levin, Daniel Krofcheck, Kelly Williams, (2022). Data Science and Machine Learning for Genome Security https://doi.org/10.2172/1855003 Publication ID: 75932

Raga Krishnakumar, Anne Ruffing, (2022). OperonSEQer: A set of machine-learning algorithms with threshold voting for detection of operon pairs using short-read RNA-sequencing data PLoS Computational Biology https://doi.org/10.1371/journal.pcbi.1009731 Publication ID: 79977

Stephen Verzi, Nicholas Johnson, Kanad Khanna, Xin Zhou, Sophie Quynn, Raga Krishnakumar, Michael Smith, (2021). Malware Generation with Specific Behaviors to Improve Machine Learning-based Detectors https://doi.org/10.2172/1899508 Publication ID: 76852

Anne Ruffing, Joshua Podlevsky, Raga Krishnakumar, Chuck Smallwood, Tessa Dallo, Xavier Torres, Stephanie Kolker, John Morgan, Nathaphon King, Melissa Marsing, (2021). CERES: CRISPR Engineering for the Rapid Enhancement of Strains https://doi.org/10.2172/1820694 Publication ID: 75713

Stephen Verzi, Raga Krishnakumar, Drew Levin, Daniel Krofcheck, Callie Boskin, Kelly Williams, (2021). Data Science for Detection of Genome Editing https://www.osti.gov/servlets/purl/1889012 Publication ID: 79387

Stephen Verzi, Raga Krishnakumar, Drew Levin, Daniel Krofcheck, Callie Boskin, Kelly Williams, (2021). Data Science for Characterization of Genome Noise/Mutation https://www.osti.gov/servlets/purl/1884061 Publication ID: 79291

Matthew Hirakawa, Nikki Tjahjono, Yooli Light, Prem Chintalapudi, Steven Branda, Kimberly Butler, Raga Krishnakumar, (2021). Augmentation of Antibacterial Activity in Mesenchymal Stromal Cells Through Systems-Level Analysis and CRISPR-mediated Activation of CD14 https://doi.org/10.2172/1868446 Publication ID: 78467

Matthew Hirakawa, Raga Krishnakumar, Jerilyn Timlin, James Carney, Kimberly Butler, (2020). Gene editing and CRISPR in the clinic: Current and future perspectives Bioscience Reports https://doi.org/10.1042/bsr20200127 Publication ID: 73844

Matthew Hirakawa, Nikki Tjahjono, Yooli Light, Prem Chintalapudi, Kimberly Butler, Steven Branda, Raga Krishnakumar, (2020). Engineering mesenchymal stromal cells for anti-microbial therapy https://www.osti.gov/servlets/purl/1768163 Publication ID: 72795

Harikrishnan Jayamohan, Anupama Sinha, Raga Krishnakumar, Harrison Edwards, Tariq Younis, Jacob Trevithick, Kamlesh Patel, Michael Bartsch, (2020). Library preparation for the Oxford Minion sequencer with ‘ASPIRE’: Automated sample PrEP by indexed rotary exchange 21st International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2017 https://www.osti.gov/servlets/purl/1463418 Publication ID: 57742

Raga Krishnakumar, Catherine Branda, Steven Branda, Kimberly Butler, Nikki Tjahjono, Yooli Light, (2019). Characterizing and Engineering Mesenchymal Stromal Cells for Anti-Microbial Therapy https://www.osti.gov/servlets/purl/1643235 Publication ID: 66184

Catherine Mageeney, Britney Lau, Steven Branda, Anupama Sinha, Raga Krishnakumar, Kelly Williams, (2019). Computational front end to diverse therapeutic phage cocktails https://www.osti.gov/servlets/purl/1643273 Publication ID: 66274

Chuck Smallwood, Anne Ruffing, Joshua Podlevsky, Raga Krishnakumar, Stephanie Kolker, Valerie Hines, (2019). Accelerating Photosynthetic Adaptations to Environmental Responses in Synechococcus sp. PCC 7002 https://www.osti.gov/servlets/purl/1642053 Publication ID: 64987

Raga Krishnakumar, Matthew Hirakawa, Nikki Tjahjono, Albert Talin, Carlos Casadevall, (2019). Capturing and modifying cell fates ? bioengineering interfaces and informatics https://www.osti.gov/servlets/purl/1641658 Publication ID: 70490

Raga Krishnakumar, Callie Boskin, Drew Levin, Daniel Carmody, Patrick Finley, Stephen Verzi, Kelly Williams, James Carney, (2019). Data Science for Detection of Genome Editi https://www.osti.gov/servlets/purl/1645734 Publication ID: 70337

Carlos Casadevall, James Calvo, Yiyang Li, Elliot Fuller, Matthew Hirakawa, Raga Krishnakumar, Albert Talin, (2019). INKJET-PRINTED ORGANIC REDOX TRANSISTORS FOR NEUROMORPHICS AND NEURAL INTERFACING https://www.osti.gov/servlets/purl/1807129 Publication ID: 69964

Catherine Mageeney, Alecia Rokes, Britney Lau, Steven Branda, Anupama Sinha, Raga Krishnakumar, Kelly Williams, (2019). Computational front end to diverse therapeutic phage cocktails https://www.osti.gov/servlets/purl/1641506 Publication ID: 70235

Prem Chintalapudi, Matthew Hirakawa, Nikki Tjahjono, Steven Branda, Kimberly Butler, Raga Krishnakumar, (2019). CRISPR-based Genetic Engineering of Mesenchymal Stem Cells https://www.osti.gov/servlets/purl/1641290 Publication ID: 69980

Catherine Mageeney, Kelly Williams, Steven Branda, Raga Krishnakumar, (2019). Diverse therapeutic phage cocktails through a computational front end https://www.osti.gov/servlets/purl/1640653 Publication ID: 68942

Catherine Mageeney, Alecia Rokes, Britney Lau, Steven Branda, Raga Krishnakumar, Kelly Williams, (2019). Computational front end to diverse therapeutic phage cocktails https://www.osti.gov/servlets/purl/1640900 Publication ID: 69317

Anne Ruffing, Raga Krishnakumar, Chuck Smallwood, Joshua Podlevsky, Stephanie Kolker, Valerie Hines, (2019). Development of Genetic and Computational Tools for CRISPRi/a Screening in Synechococcus sp. PCC 7002 https://www.osti.gov/servlets/purl/1640704 Publication ID: 68882

Catherine Mageeney, Alecia Rokes, Briney Lau, Steven Branda, Raga Krishnakumar, Kelly Williams, (2019). Diverse therapeutic phage cocktails through a computational front end https://www.osti.gov/servlets/purl/1639435 Publication ID: 67521

Raga Krishnakumar, Anupama Sinha, Sara Bird, Harikrishnan Jayamohan, Harrison Edwards, Joseph Schoeniger, Kamlesh Patel, Steven Branda, Michael Bartsch, (2018). Systematic and stochastic influences on the performance of the MinION nanopore sequencer across a range of nucleotide bias Scientific Reports https://doi.org/10.1038/s41598-018-21484-w Publication ID: 58764

Michael Bartsch, Sara Bird, Steven Branda, Harrison Edwards, Harikrishnan Jayamohan, Raga Krishnakumar, Kamlesh Patel, Joseph Schoeniger, Anupama Sinha, (2018). Real-Time Automated Pathogen Identification by Enhanced Ribotyping (RAPIER) LDRD Final Report https://doi.org/10.2172/1481615 Publication ID: 59412

Yooli Light, Matthew Hirakawa, Nikki Tjahjono, Steven Branda, Kimberly Butler, Raga Krishnakumar, (2018). Mesenchymal stem cell-based therapy for infectious disease https://www.osti.gov/servlets/purl/1594331 Publication ID: 59391

Michael Bartsch, Steven Branda, Raga Krishnakumar, Anupama Sinha, Harrison Edwards, Sara Bird, Harikrishnan Jayamohan, Kamlesh Patel, (2018). LDRD Ending Project ReviewReal-time Automated Pathogen Identification by Enhanced Ribotyping (RAPIER) https://www.osti.gov/servlets/purl/1806834 Publication ID: 58981

Navya Peddireddy, Nikki Tjahjono, Raga Krishnakumar, Yooli Light, (2018). Developing Genetically and Chemically Converted Stem Cells for Cell Therapy https://www.osti.gov/servlets/purl/1806706 Publication ID: 63278

Michael Bartsch, Raga Krishnakumar, Anupama Sinha, Kamlesh Patel, Harrison Edwards, (2018). Real-Time Selective Sequencing with RUBRIC (Read Until with Basecall- and Reference-Informed Criteria) https://www.osti.gov/servlets/purl/1515754 Publication ID: 62185

Michael Bartsch, Harrison Edwards, Raga Krishnakumar, Anupama Sinha, Kamlesh Patel, (2018). The Evolution of MinION Selective Sequencing: Read Until with Basecall- and Reference-Informed Criteria (RUBRIC) https://www.osti.gov/servlets/purl/1501983 Publication ID: 61115

Michael Bartsch, Harrison Edwards, Raga Krishnakumar, Anupama Sinha, Kamlesh Patel, (2018). Read Until with Basecall- and Reference-Informed Criteria https://www.osti.gov/servlets/purl/1501982 Publication ID: 61116

Michael Bartsch, Raga Krishnakumar, Anupama Sinha, Kamlesh Patel, Harrison Edwards, (2018). Read Until with Basecall- and Reference Informed Criteria (RUBRIC) https://www.osti.gov/servlets/purl/1501981 Publication ID: 61117

Michael Bartsch, Raga Krishnakumar, Anupama Sinha, Joseph Schoeniger, Steven Branda, Kamlesh Patel, Harrison Edwards, Sara Bird, Harikrishnan Jayamohan, (2018). Characterizing the Performance of the MinION for Real-Time Detection https://www.osti.gov/servlets/purl/1503084 Publication ID: 61161

Raga Krishnakumar, Michael Bartsch, Kamlesh Patel, Steven Branda, Joseph Schoeniger, Harrison Edwards, Sara Bird, Harikrishnan Jayamohan, (2017). Selective Long-Read Nanopore Sequencing for Real-Time Point-of-need Pathogen Identification https://www.osti.gov/servlets/purl/1511977 Publication ID: 54662

Britney Lau, Raga Krishnakumar, Julian Wagner, Anupama Sinha, Corey Hudson, Joseph Schoeniger, Steven Branda, Kelly Williams, (2017). Discovering and converting temperate phages for therapy https://www.osti.gov/servlets/purl/1483224 Publication ID: 54346

Raga Krishnakumar, (2017). Harnessing the power of genomics for detection diagnosis and mechanistic analysis of cellular responses https://www.osti.gov/servlets/purl/1480221 Publication ID: 53797

Raga Krishnakumar, Harrison Edwards, Anupama Sinha, Sara Bird, Kamlesh Patel, Michael Bartsch, (2017). Selective Long-Read Nanopore Sequencing for Rapid Real-Time Pathogen Identification https://www.osti.gov/servlets/purl/1510603 Publication ID: 53467

Harikrishnan Jayamohan, Anupama Sinha, Raga Krishnakumar, Harrison Edwards, Tariq Younis, Jacob Trevithick, Kamlesh Patel, Michael Bartsch, (2017). Library Preparation and Analysis Methods for the Oxford MinION Nanopre Sequencer for Pathogen Identification https://www.osti.gov/servlets/purl/1481358 Publication ID: 53994

Sankalp Sinha, Raga Krishnakumar, Kelly Williams, Joseph Schoeniger, (2017). Comparative Analysis between Genomic Islands and Host Species https://www.osti.gov/servlets/purl/1508231 Publication ID: 57547

Kelly Williams, Britney Lau, Raga Krishnakumar, Julian Wagner, Corey Hudson, Joseph Schoeniger, (2017). Reconsidering temperate phages for therapy https://www.osti.gov/servlets/purl/1458119 Publication ID: 56671

Kelly Williams, Raga Krishnakumar, Julian Wagner, Corey Hudson, Joseph Schoeniger, Kelly Williams, (2017). The Bacterial and Archaeal Pan-Mobilome https://www.osti.gov/servlets/purl/1456320 Publication ID: 55476

Harikrishnan Jayamohan, Michael Bartsch, Raga Krishnakumar, Kamlesh Patel, Steven Branda, Anupama Sinha, Harrison Edwards, Daniel Throckmorton, Sara Bird, Joseph Schoeniger, (2017). Nanopore Sequencing for Real-Time Pathogen Identification https://www.osti.gov/servlets/purl/1507629 Publication ID: 55103

Michael Bartsch, Raga Krishnakumar, Anupama Sinha, Sara Bird, Joseph Schoeniger, Kamlesh Patel, (2016). Real-Time Automated Pathogen Identification by Enhanced Ribotyping (RAPIER) https://www.osti.gov/servlets/purl/1422120 Publication ID: 48006

Showing Results. Show More Publications

Selected Publications

  • Publications may be viewed through the NCBI Collection.
  • Krishnakumar R, Gamble MJ, Frizzell KM, Berrocal JG, Kininis M, Kraus WL. Reciprocal binding of PARP-1 and histone H1 at promoters specifies transcriptional outcomes. Science (New York, N.Y.). 2008; 319(5864):819-21.
  • Zhang T, Berrocal JG, Frizzell KM, Gamble MJ, DuMond ME, Krishnakumar R, Yang T, Sauve AA, Kraus WL. Enzymes in the NAD+ salvage pathway regulate SIRT1 activity at target gene promoters. The Journal of biological chemistry. 2009; 284(30):20408-17.
  • Frizzell KM, Gamble MJ, Berrocal JG, Zhang T, Krishnakumar R, Cen Y, Sauve AA,Kraus WL. Global analysis of transcriptional regulation by poly(ADP-ribose) polymerase-1 and poly(ADP-ribose) glycohydrolase in MCF-7 human breast cancer cells. The Journal of biological chemistry. 2009; 284(49):33926-38.
  • Gamble MJ, Frizzell KM, Yang C, Krishnakumar R, Kraus WL. The histone variant macroH2A1 marks repressed autosomal chromatin, but protects a subset of its target genes from silencing. Genes & development. 2010; 24(1):21-32.
  • Krishnakumar R, Kraus WL. The PARP side of the nucleus: molecular actions, physiological outcomes, and clinical targets. Molecular cell. 2010; 39(1):8-24.
  • Krishnakumar R, Kraus WL. PARP-1 regulates chromatin structure and transcription through a KDM5B-dependent pathway. Molecular cell. 2010; 39(5):736-49.
  • Zhang T, Berrocal JG, Yao J, DuMond ME, Krishnakumar R, Ruhl DD, Ryu KW, Gamble MJ, Kraus WL. Regulation of poly(ADP-ribose) polymerase-1-dependent gene expression through promoter-directed recruitment of a nuclear NAD+ synthase. The Journal of biological chemistry. 2012; 287(15):12405-16.
  • Krishnakumar R, Blelloch RH. Epigenetics of cellular reprogramming. Current opinion in genetics & development. 2013; 23(5):548-55.
  • Luo X, Chae M, Krishnakumar R, Danko CG, Kraus WL. Dynamic reorganization of the AC16 cardiomyocyte transcriptome in response to TNFα signaling revealed by integrated genomic analyses. BMC genomics. 2014; 15:155.
  • Parchem RJ, Ye J, Judson RL, LaRussa MF, Krishnakumar R, Blelloch A, Oldham MC, Blelloch R. Two miRNA clusters reveal alternative paths in late-stage reprogramming. Cell stem cell. 2014; 14(5):617-31.
  • Krishnakumar R, Chen AF, Pantovich MG, Danial M, Parchem RJ, Labosky PA, Blelloch R. FOXD3 Regulates Pluripotent Stem Cell Potential by Simultaneously Initiating and Repressing Enhancer Activity. Cell stem cell. 2016; 18(1):104-17.
  • Freimer JW, Krishnakumar R, Cook MS, Blelloch R. Expression of Alternative Ago2 Isoform Associated with Loss of microRNA-Driven Translational Repression in Mouse Oocytes. Current biology: CB. 2018; 28(2):296-302.e3.
  • Krishnakumar R, Sinha A, Bird SW, Jayamohan H, Edwards HS, Schoeniger JS, Patel KD, Branda SS, Bartsch MS. Systematic and stochastic influences on the performance of the MinION nanopore sequencer across a range of nucleotide bias. Scientific reports. 2018; 8(1):3159.
  • Chen AF, Liu AJ, Krishnakumar R, Freimer JW, DeVeale B, Blelloch R. GRHL2-Dependent Enhancer Switching Maintains a Pluripotent Stem Cell Transcriptional Subnetwork after Exit from Naive Pluripotency. Cell stem cell.018.

Awards, Honors, and Memberships

  • A.P. Giannini Medical Research Fellow, 3-year Postdoctoral Fellowship (2011-2014)
  • NIH Ruth L. Kirschstein National Research Service Award (NRSA) Institutional Research Training Grant-Parent T32 (2011)
  • Predoctoral Fellowship, American Heart Association (2008-2010)