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MatheeNarasimhan, Kalai

Title: Professor

Office: AHC4 223 (O); AHC4 241 (L)

Phone: 305-348-0628

Email: matheek@fiu.edu

Department(s): Human and Molecular Genetics




Dr. Mathee is the first founding faculty member and founding chairman of the Department of Molecular Microbiology and Infectious Diseases. A native of Malaysia, Dr. Mathee is a dedicated and demanding teacher who has received high praises from her students. She received BSc (Genetics) and M Sc (Microbial Genetics) degrees from the University of Malaya and went on to complete her Ph.D. in Molecular Microbiology at the University of Tennessee, Memphis under the tutelage of Martha M. Howe. Her fascination with Pseudomonas aeruginosa and cystic fibrosis (CF) started in 1993 when she joined Dennis Ohman's lab as a postdoctoral fellow. This led her to spend time in Copenhagen working with Niels Hoiby and Soren Molin on various aspects of the infections that ultimately lead to the pulmonary failure in CF patients. In 1999, she joined the Department of Biological Sciences at FIU as an Assistant Professor of Pathogenic Microbiology. Dr. Mathee has established a multi-faceted research program focused on molecular pathogenesis in the model organism Pseudomonas aeruginosa that is responsible for the high morbidity and mortality in CF patients. She is very passionate about her research and how it might contribute to increasing cystic fibrosis patient quality of life. She is well-respected nationally and internationally by researchers in multiple fields, including Pseudomonas pathogenesis, alternate therapy using botanicals, microbial biofilm development, regulation of prokaryotic transcription and phage molecular biology. She has published more than 50 articles and several book chapters in the fields of molecular microbiology, forensic science and bioinformatics - many of which are recognized as seminal and have been selected for journal highlights. In 2008, one of her papers was selected by the Faculty of 1000 Biology members, a much-coveted honor. www.fiu.edu/~matheek

In 2011, she received the Mentor of the year award and was bestowed the highest honorof her career in FIU, the President's Council Worlds Ahead Faculty Award in recognition of outstanding achievement as a student-centered professor who makes an impact and exceeds expectations (http://www.youtube.com/watch?v=wacRdh0ekiQ)

She serves as Editor of Journal of Medical Microbiology and BMC Microbiology.

Research

The main focus of my research since Fall 1993 can be summarized as the "Molecular Genetic Studies of Bacterial Pathogenicity Using Pseudomonas aeruginosa as the Model Organism". In addition, I also work on bioinformatics, comparative genomics and microbial metagenomic profiling.
P. aeruginosa is an opportunistic bacterium that causes a variety of severe and sometimes lethal infections of the respiratory tract, urinary tract, intestine, eyes, ears, and wounds. It has become a serious threat to immuno-compromised patients, and it is increasingly difficult to treat due to both intrinsic and acquired resistance to multiple anti-microbial agents. Chronic infection with P. aeruginosa remains the most common cause of morbidity and mortality among patients with cystic fibrosis (CF), an inherited disease among Caucasians, afflicting 1 in 3500 live births in the USA. Antibiotic therapy, with a mixture of aminoglycoside and ß-lactam antibiotics, is most often prescribed. However, such treatment often fails in CF patients due to the emergence of resistant strains that have a mucoid appearance. My area of research on this organism can be subdivided into five subsections:

  • Molecular mechanism of mucoid conversion. The mucoid appearance is caused by production of a capsule-like polysaccharide called alginate. The organism uses a complex circuitry to control the expression of the genes that lead to the production of alginate and that ultimately kill CF patients. Since 1993, I have worked on a number of questions related to alginate gene regulation and the role of alginate in the infectious process.
  • Molecular mechanism of resistance to ß-lactam antibiotics. In 1999, I realized that the genetic events underlying the resistance mechanism, especially to ß-lactam antibiotics in P. aeruginosa, had not been clearly elucidated. This area is the major focus in my lab. I was able to get continuous federal funding for this project. Since my sabbatical in 2006, we collaborate with Steve Lory (Harvard Medical School) on genomics and proteomics analyses.
  • Alternative and complementary therapy. In addition, I have been very interested in exploring alternative and complementary therapy for patients suffering from chronic P. aeruginosa infections. The focus is on P. aeruginosa quorum sensing (QS) that is critical for its ability to establish and maintain infections. Two major aspects of this project are exploring antimicrobial compounds from South Florida medicinal plants and exploring the role of ginseng in modulating the disease outcome. In addition we are also screening synthetic compounds with potential anti-quorum sensing activities. This is a collaborative research effort with John Makemson (Department of Biological Sciences), Steve Wnuk and Martin Quirke (Dept of Chemistry & Biochemistry) and Fred Ausubel (Harvard Medical School)
  • CF sputum ecology. Only 5% of the microbes in nature are culturable, we hypothesize that the routine culturable methods currently being used for the identification of bacterial pathogens from CF sputa yield limited microbiological information, and fail to identify numerous pathogenic bacterial species that are potentially present in the airways of CF patients. We have been using molecular methods for the direct detection of specific microorganisms in the heterogeneous CF sputum samples. This is a collaborative research with University of Miami Cystic Fibrosis Center (Dr. Michael Light) and Miami Children's Hospital (Dr. Maria Franco and Dr. Simpser).

Selected Publications

1. 2012. L. Schenepr. N. Maricic, and K. Mathee. Panax ginseng as a potential antibacterial therapeutic agent. 2011 special issue of the International Journal of Biomedical and Pharmaceutical Sciences – In Press

2. 2012. E. Zheng, C. Ding, K. Mathee, L. Schneper and G. Narasimhan. Semantic similarity between genes and its applications in function prediction and functional network generation. Data mining: Medical, Health, Social and Biological Applications. D.E. Holmes (Ed.), Springer. [Peer Reviewed] In Press.

3. 2012. L. Schneper, N. Maricic, K. Mathee. Anti-quorum sensing, anti-bacterial, and immunomodulatory properties of Panax ginseng. International Journal of Biomedical and Pharmaceutical Sciences 6:11-24. [Peer Reviewed]

4. 2012. D. Balasubramanian, L. Schnepper, M Merighi, R. Smith, S. Lory, and K. Mathee. The regulatory repertoire of Pseudomonas aeruginosa AmpC ß-lactamase regulator AmpR includes multiple virulence genes. PLoS One 7(3):e34067. [Peer Reviewed]

5. 2012. R. Sautter, D. Ramos, O. Ciofu, A. Heydorn, N. Hoiby, A. Kharazmi, C. DeVries, D.E. Ohman, L. Schneper, and K. Mathee. A complex multilevel attack on Pseudomonas aeruginosa algT/U expression and AlgT/U activity results in the loss of alginate production. Gene 498(2):242-53. [Peer Reviewed]

6. 2011. C.Z. Li, K. Vandenberg, S. Prabhulkar, X. Zhu, L. Schneper, K. Mathee, C.J. Rosser, and E. Almeide. Paper based point-of-care testing disc for multiplex whole cell bacteria analysis. Biosensors and Bioelectronics 26:4342-8.

7. 2011. K.G. Chan, S. Atkinson, K. Mathee, C.K. Sam, S.R. Chhabra, M. Cámara, C.L. Koh, and P. Williams. Characterization of N-acylhomoserine lactone-degrading bacteria associated with the Zingiber officinale (ginger) rhizosphere: co-existence of quorum quenching and quorum sensing in Acinetobacter and Burkholderia. BMC Microbiology 11:51.

  • It has been designated as "Highly accessed" paper. The 'Highly accessed' designate identifies those articles that have been especially highly accessed, relative to their age, and the

8. 2011.D. Balasubramanian, K.F. Kong, S. Jayawardena, S. Leal, R. Sautter, and K. Mathee. Coregulation of ß-lactam resistance, alginate production, and quorum sensing in Pseudomonas aeruginosa. Journal of Medical Microbiology 60(2):147-156.

  • Featured in MDLinx web site (www.MDLinx.com). MDLinx is the world's most up-to-date index of articles that matter in the daily lives of physicians and other healthcare professionals.

9. 2010.K. F. Kong, L. Schneper, and K. Mathee. Beta-lactam antibiotics: from antibiosis to resistance and bacteriology. Review. Acta Pathologica, Microbiologica, et Immunologica Scandinavica 118(1):1-36 [Peer Reviewed]

  • Listed as a paper "of outstanding interest" by Llarrull et al, 2010 Current Opinion in Microbiology 13:551-557.

10. 2010. K.F. Kong, A. Aguila, L. Schneper, and K. Mathee. Pseudomonas aeruginosa β-lactamase induction requires two permeases, AmpG and AmpP. BMC Microbiology 10:328-343.

  • It has been designated as "Highly accessed" paper.

11. 2010. S. Cardenas, M. Scuri, L. Samsell, B. Ducatman, P. Bejarano, A. Auais, M. Doud, K. Mathee, and G. Piedimonte. Neurotropic and neuroimmune responses to early-life Pseudomonas aeruginosa infection in rat lungs. American Journal of Physiology - Lung Cellular and Molecular Physiology 299(3): L334-44.

12. 2010. Z. Song, K.F Kong, H. Wu, N. Maricic, B. Ramalingam, H. Priestap, J.M.E. Quirke, N. Høiby, L. Schneper and K. Mathee. Panax ginseng has anti-infective activity against opportunistic pathogen Pseudomonas aeruginosa by inhibiting quorum sensing, a bacterial communication process critical for establishing infection. Phytomedicine 17(13):1040-1046.

13. 2010. M.S. Doud, M. Light, G. Gonzalez, G. Narsimhan, and K. Mathee. Combination of 16S rRNA variable regions provides a detailed analysis of bacterial community dynamics in the lungs of cystic fibrosis patients. Human Genomics 4(3):147-169.

14. 2010. K. Mathee. Magic of Life. Article written for the Sequentia Exhibit at the Patricia and Phillip Frost Art Museum, October 2010-January 2011; http://www.xaviercortada.com/event/id/69469/Sequentia-a-solo-exhibit-at-the-Frost-Art-
Museum.htm

15. 2009. M. Doud, E. Zeng, L. Schneper, G. Narasimhan, K. Mathee. Approaches to analyzing dynamic microbial communities such as those seen in cystic fibrosis lung. Human Genomics 3(3):246-256. [Peer Reviewed]

16. 2009. M. Herzberg, T. Rezene, C. Ziemba, O. Gillor, and K. Mathee. Impact of higher alginate expression on deposition of Pseudomonas aeruginosa in radial stagnation point flow and reverse osmosis systems. Environmental Science & Technology Journal 43(19):7376-
7383.

17. 2009. M.S. Doud, R. Grimes-Zeppegno, E. Molina, N. Miller, D. Balachandar, L. Schneper, R. Poppiti, and K. Mathee. A k2A-positive Klebsiella pneumoniae causes liver and brain abscess in a Saint Kitt's man. International Journal of Medical Sciences 6(6):301-304.

18. 2009. D. Balasubramanian, and K. Mathee. Comparative transcriptome analyses of Pseudomonas aeruginosa. Human Genomics 3(4):349-61.

19. 2009. G. Gonzalez, M. Doud, K. Mathee and G. Narasimhan. Computer-assisted bacterial identification using 16S rRNA sequence data. Book series: FMBE Proceedings 24:239- 249. [Peer Reviewed]

20. 2008. K. Mathee, G. Narasimhan, C. Valdes, X. Qiu, J. M. Matewish , M. Koehrsen, A. Rokas, C. N. Yandava, R. Engels, E. Zeng, R. Olavarietta, M. Doud, R. Smith , P. Montgomery, J. White, P. A. Godfrey, C. Kodira, B. Birren, J. Galagan and S. Lory. Dynamics of Pseudomonas aeruginosa genome evolution. Proceedings of National Academy of Sciences 105:3100-3105.
Highlighted by

  • Genome Technology Online, Feb 20, 2008, "Survival through genome shapeshifting"
  • Selected for review by Faculty of 1000 Biology

21. 2008. Attenuation of Pseudomonas aeruginosa virulence by medicinal plants in a Caenorhabditis elegans model system. A. Adonizio, S.M, Leal Jr, F.M. Ausubel FM, K. Mathee. Journal of Medical Microbiology 57:809-813.

22. 2008. S. Roy S, H. Vedala, A.D. Roy, D.H. Kim, M. Doud, K. Mathee, H.K. Shin, N. Shimamoto, V. Prasad and W. Choi. Direct electrical measurements on single-molecule genomic DNA using single-walled carbon nanotubes. Nano Letters 8:26-30.
Highlighted by

  • Nanowerk Spotlight, Dec 28, 2007, "DNA electronics in nanotechnology"
  • NewScientist Tech, Dec 4, 2007, "Nanoelectrodes could provide bird flu test"
  • NewScientist, "Nantube electrodes could provide avian flu test"
  • NanoScienceWorks, jan 2008, "Nanotube electrodes can "match" DNA via signals"
  • Technology Reviews, February 13, 2008, "Wiring up DNA"
  • Nature Spotlight on a related article that appeared in Feb 2008 included our work.

23. 2008. A. L. Adonizio, K.F. Kong, and K. Mathee. Inhibition of quorum sensing-controlled virulence factor production in Pseudomonas aeruginosa by South Florida plant extracts. Antimicrobial Agents and Chemotherapy 52:198-203.

24. 2007. E. Zeng, K. Mathee, and G. Narasimhan. IEM: an algorithm for iterative enhancement of motifs using comparative genomics data. Computional System Bioinformatics Conference Proceedings 6:227-35.

25. 2007. D.K. Mills, J.A. Entry, K. Mathee, and P.M. Gillevet. Mini-Review: Assessing Microbial Community Diversity Using Amplicon Length Heterogeneity PCR. Soil Science Society of America Journal (71 March-April).

26. 2007. C. Yang, E. Zheng, K. Mathee, and G. Narasimhan. PlasmoTFBM: An intelligent queriable database for predicted transcription factor binding motifs in Plasmodium falciparum. Methods in Microarray Data Analysis V: 121-136. McConnell, Lin, Hurban (Eds.), Springer.

27. 2006 L.I. Moreno, D. K. Mills, J. Entry, R.T. Sautter, and K. Mathee. Microbial metagenome profiling using Amplicon Length Heterogeneity-Polymerase Chain Reaction (ALH-PCR) proves more effective than elemental analysis in discriminating soil specimens. Journal of Forensic Science 51:1315-1322.

28. 2006. D.K. Mills, J. A. Entry, J.D. Voss, P.M. Gillevet, and K. Mathee. An assessment of the hypervariable domains of the 16S rRNA genes for their value in determining microbial community diversity: the paradox of traditional ecological indices. FEMS Microbiological Ecology 57:496-503.

29. 2006 A. L. Adonizio, K. Downum, B. C. Bennett, and K. Mathee. Anti-quorum sensing activity of medicinal plants in southern Florida. Journal of Ethnopharamocology 105:427-35.

30. 2006. J. Makemson, A. Eberhard, and K. Mathee. Simple electrospray mass spectrometry detection of acylhomoserine lactones. Luminescence 21:1-6.

31. 2006. S.Z. Miller, S. King, and K. Mathee. Forensic DNA analysis: An overview of human DNA analysis. International Journal of Forensic Science (Revista de Ciencias Forenses) 1:31-38.

32. 2006. C. Yang, D. Mills, K. Mathee, Y. Wang, K. Jayachandran, M. Sikaroodi, P. Gillevet, J. Entry, and G. Narasimhan. Ecoinformatics tools for microbial diversity studies: Supervised classification of amplicon length heterogeneity (ALH) profiles of 16S rRNA. Journal of Microbiological Methods 65: 49-62.

33. 2005. K.F. Kong, S.R. Jayawardena, S. D. Indulkar, A. del Puerto, C-L. Koh, N. Høiby, and K. Mathee. Pseudomonas aeruginosa AmpR is a global transcriptional factor that regulates expression of AmpC and PoxB ß-lactamases, proteases, quorum sensing and other virulence factors. Antimicrobial Agents and Chemotherapy 49:4567-75.

  • Article selected for Journal Highlights in the ASM News December issue. A monthly issue that highlights one article per journal that describes new and exciting developments in microbial research.

34. 2005, K.F. Kong, S.R. Jayawardena, A. Del Puerto, L. Wiehlmann, U. Laabs, B. Tummler, and K. Mathee. Characterization of poxB, a chromosomal-encoded Pseudomonas aeruginosa oxacillinase. Gene 358:82-92