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Scholarly Interest Report
         
Natasha Kirienko
Assistant Professor
Assistant Professor of BioSciences
 
e-mail:kirienko@rice.edu
 
  • BS Biochemistry (2002) Southern Federal University, Russia
  • PhD Molecular Biology (2009) University of Wyoming
  • MS Biology (2004) Southern Federal University, Russia
 
Primary Department
   Department of BioSciences
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Websites
 Kirienko Lab Website
 
Research Areas
 Using C. elegans as a model system to study the conserved mechanisms of organismal defenses to stresses and infection with pathogens
 

Research Statement

 

Kirienko's Research


We use the model organism Caenorhabditis elegans to study the conserved mechanisms (immune and otherwise) that are used by the organism to defend itself against abiotic (i.e., environmental) and biological (i.e., pathogenic) stresses. C. elegans is a small, bacteriovorous nematode. It offers several invaluable traits for the modern biomedical researcher, including its small size (allowing it to be rapidly grown in the lab in high numbers), quick generation time (facilitating work ranging from biochemical to genetic to pathogenesis research), and even its transparency (enabling straight-forward use of fluorescent proteins and bioluminescence, as well as general imaging), and a genetic toolkit that is nearly unrivaled in other model organisms. In addition, C. elegans is often susceptible to infection with many of the same pathogenic bacteria as humans, and infection frequently utilizes the same virulence factors. This, combined with the remarkable conservation of innate immune pathways, makes C. elegans an attractive target for infectious disease models.


Research in my lab currently focuses on two interrelated topics. The first of these goals is to identify novel treatments for bacterial infections that exhibit resistance to antimicrobials. Antimicrobial resistant bacteria cause over 1.5 million nosocomial infections per year, and over 100,000 deaths. As antimicrobial misuse continues at a virtually unchecked pace, resistance has flourished, making new treatments desperately needed. We've developed a liquid-based, Pseudomonas aeruginosa infection assay that utilizes the master virulence factor pyoverdin for pathogenesis. Using this assay, we've identified small molecules that inhibit P. aeruginosa virulence or that promote innate immune activation. Research within the past twenty years has increasingly demonstrated that innate immunity plays a crucial role in priming the adaptive immune response and in mitigating the earliest sequelae of infection.


We have recently begun to study the importance of mitophagy (autophagic destruction of mitochondria) in cancer as well. Much contradictory evidence exists in the scientific literature suggesting that autophagy in general (and mitophagy in particular) may have pro-oncogenic effects (e.g., promoting organellar and protein complex recycling and efficient use of cellular energy reserves) and also anti-tumorigenic effects (e.g., mutation or loss of much of the autophagic and mitophagic machinery of the cell, or their regulators are strongly associated with increased cancer prevalence). We will utilize the C. elegans and human cells to gain an understanding of the relevance of mitophagy in tumor initiation and progression. This research effort will harness the particularly deep knowledge base of C. elegans cell cycle events that has been amassed by researchers across the globe over the past thirty years and leverage the high-throughput capabilities of < em> C. elegans assays to identify novel therapies that may help cancer patients.

 
Selected Publications
 Refereed articles
 

Kirienko DR, Revtovich AV, Kirienko NV "A High-Content, Phenotypic Screen Identifies Fluorouridine as an Inhibitor of Pyoverdine Biosynthesis and Pseudomonas aeruginosa Virulence." mSphere, 1: e00217-16.

 
 

Tjahjono E, Kirienko NV "A Conserved Mitochondrial Surveillance Pathway Is Required for Defense against Pseudomonas aeruginosa ." Submitted

 
 

Kirienko NV, Ausubel FM, Ruvkun G "Mitophagy confers resistance to siderophore-mediated killing by Pseudomonas aeruginosa." Proc Natl Acad Sci U S A., 112 (2015) : 1821-6.

 
 

Conery AL, Larkins-Ford J, Ausubel FM, Kirienko NV "High-throughput screening for novel anti-infectives using a C. elegans pathogenesis model." Curr Protoc Chem Biol, 6 (2014) : 25-37.

 
 

Kirienko NV, Cezairliyan BO, Ausubel FM, Powell JR "Pseudomonas aeruginosa PA14 pathogenesis in Caenorhabditis elegans." Methods Mol. Biol., 1149 (2014) : 653-69.

 
 

Kuzmanov A, Karina EI, Kirienko NV, Fay DS "The conserved PBAF nucleosome-remodeling complex mediates the response to stress in Caenorhabditis elegans." Mol. Cell. Biol., 34 (2014) : 1121-35.

 
 

Pellegrino MW, Nargund AM, Kirienko NV, Gillis R, Fiorese CJ, Haynes CM "Mitochondrial UPR-regulated innate immunity provides resistance to pathogen infection." Nature, 516 (2014) : 414–417.

 
 

Kirienko NV, Larkins-Ford J, Wählby C, Ruvkun G, Ausubel FM "Pseudomonas aeruginosa disrupts Caenorhabditis elegans iron homeostasis, causing a hypoxic response and death." Cell Host Microbe, 13 (2013 ) : 406-16.

 
 

Riedel CG, Dowen RH, Lourenco GF, Kirienko NV, Heimbucher T, West JA, Bowman SK, Kingston RE, Dillin A, Asara JM, Ruvkun G "DAF-16 employs the chromatin remodeller SWI/SNF to promote stress resistance and longevity." Nat. Cell Biol., 15 (2013) : 491-501.

 
 

McEwan DL, Kirienko NV, Ausubel FM "Host translational inhibition by Pseudomonas aeruginosa Exotoxin A Triggers an immune response in Caenorhabditis elegans." Cell Host Microbe, 11 (2012) : 364-74.

 
 

Pukkila-Worley R, Feinbaum R, Kirienko NV, Larkins-Ford J, Conery AL, Ausubel FM "Stimulation of Host Immune Defenses by a Small Molecule Protects C. elegans from Bacterial Infection." PLoS Genet., 8 (2012) : e1002733.

 
 

Sait M, Kamneva OK, Fay DS, Kirienko NV, Polek J, Shirasu-Hiza MM, Ward NL "Genomic and Experimental Evidence Suggests that Verrucomicrobium spinosum Interacts with Eukaryotes." Front Microbiol, 2 (2011) : 211.

 
 

Kirienko NV, Fay DS "SLR-2 and JMJC-1 regulate an evolutionarily conserved stress-response network." EMBO J., 29 (2010) : 727-39.

 
 

Kirienko NV, Mani K, Fay DS "Cancer models in Caenorhabditis elegans." Dev. Dyn., 239 (2010) : 1413-48.

 
 

Barends TR, Hartmann E, Griese JJ, Beitlich T, Kirienko NV, Ryjenkov DA, Reinstein J, Shoeman RL, Gomelsky M, Schlichting I "Structure and mechanism of a bacterial light-regulated cyclic nucleotide phosphodiesterase." Nature , 459 (2009) : 1015-8.

 
Presentations
 Invited Talks
 

Texas A&M: Center for Infection and Inflammatory Diseases, November 2016, Houston, TX

 
 Keynote Speaker
 

Rice University, Houston: GCURS. Keynote address, October 2016. Houston, TX

 
 

Rice University, Houston: Graduate Student Symposium.

Keynote address, August 2015. Houston, TX. 

 
 Panelist
 

MD Anderson Cancer Center:43rd Annual Meeting of the Texas Genetics Society

April 2016, Houston, TX

 
 Posters
 

Rice Summer Undergraduate Research Programs. Jaffe A, Tjahjono E, Kirienko N. “High Throughput Screening for Novel Mitophagy Activators in C. elegans”, August 2016, Houston TX

 
 

Rice Summer Undergraduate Research Programs. Ashok B, Kirienko N. “Identification of Genes Mutated in Cancer that Activate Mitophagy in C. elegans”, August 2016, Houston TX

 
 

Rice Summer Undergraduate Research Programs. Lee J, Tjahjono E, Kirienko N. “Identification of Pro-Oncogenic Transformations Sensitive to Mitophagic Activation”, August 2016, Houston TX

 
 

Rice Undergraduate Research Symposium. Kang D, Kirienko N. “Identification of Small Molecules that Block Pyoverdine Toxicity”, April 2016, Houston TX

 
 

Rice Summer Undergraduate Research Programs. Yu H, Kirienko N. “Identifying and Differentiating between Pyoverdine Fractions”, August 2016, Houston TX

 
 

Rice Summer Undergraduate Research Programs. Kang D, Kirienko N. “Media Dependent Regulation of Cytotoxic Siderophore in P. aeruginosa”, August 2016, Houston TX

 
 

GCURS. Kang D, Kirienko N. “Mutations in Surface Attachment Factors Disrupt Pyoverdine Production in P. aeruginosa”, October 2016, Houston TX

 
 

Rice Summer Undergraduate Research Programs. Lee R, Kirienko N. “OP50 and HT115 as Food Sources Affect C. elegans Survival”, August 2016, Houston TX

 
 

43rd Annual Meeting of the Texas Genetics Society Kang D, Kirienko N. “Pel Exopolysaccharide Regulates Toxic Siderophore Production in P. aeruginosa” Best Poster Award. April 2016, Houston TX

 
 

GCURS. Diaz V, Kang D, Kirienko N. “Pyoverdine Production in P. aeruginosa is Regulated by c-di-GMP in a Pel Exopolysaccharide-Dependent Manner”, October 2016, Houston TX

 
 

Rice Undergraduate Research Symposium. Bu S, Kirienko N. “Role of bZIP Family Proteins in Defense Against Pseudomonas aeruginosa”, April 2016, Houston TX

 
 

43rd Annual Meeting of the Texas Genetics Society. Hummell N, Tjahjono E, Kirienko N. “The Characterization of Novel Proteasome Activator LK16”. April 2016, Houston TX

 
 Seminar Speaker
 

Baylor College of Medicine: Houston Area Worm Group Meeting Seminar, May 2016, Houston, TX

 
 

UT Health McGovern Medical School: Bacterial Interest Group Seminar, September 2016, Houston, TX.

 
 

UT Health McGovern Medical School: Molecular Basis of Infectious Disease Seminar, July 2016, Houston, TX.

 
 

University of California, Los Angeles: 20th International Worm Meeting.

June 2015. Los Angeles, CA.

 
Supervised Theses & Dissertations
 Zheng Liu, Ph.D. Graduate Research Advisor. (Thesis Committee Member)

 Jennifer Dou, Ph.D. Graduate Research Advisor. (Thesis Committee Member)

 Cynthia Wong, Ph.D. Graduate Research Advisor. (Thesis Committee Member)

 Amy Prater, Ph.D. Graduate Research Advisor. (Thesis Committee Member)

 Amy Prater, Ph.D. Graduate Research Advisor. (Thesis Committee Member)

 Zheng Liu, Ph.D. Graduate Research Advisor. (Thesis Committee Member)

 Nicholas Hummel, Ph.D. Graduate Research Advisor. (Thesis Director)

Positions Held
 Member, Genetic Society of America. (2011 - 2015)