Department of Biomaterials Science and Engineering Laboratory
Professor, Biomaterials Science and Engineering Laboratory
B.S. Life Sciences, MIT, 1962
M.S. Food Technology, MIT,1964
M.S. Chemical Engineering, MIT ,1966
Sc.D. Food Science, MIT , 1967
The interest of the Rha lab is to determine the structure, function and properties of complex biological molecules. A wide variety of techniques, including transcriptional profiling, genomic sequencing and analysis, LC and GC mass spectroscopy, molecular imaging and micro-rheology, are employed to examine the bioactivities of living systems at the genomic and molecular level to provide the basis for identifying and engineering plants to produce natural products for medicinal and industrial use.
Natural product discovery
Natural product discovery involves the isolation and identification of bioactive compounds from natural sources. Many modern commercial medicines are derived from plants, such as aspirin, morphine, Taxol and digitalis. Vietnamese lore attributes the tree, Tongkat Ali (Eurycoma longifolia), with the capability to cure 1,000 diseases. Our findings show that some components from this tree have anti-viral, anti-cancer and androgenic properties. We have also found that some components of Centella asiatica, such as asiatic acid, exert cytotoxic effects, while other components may have protective effects to counter the toxicity.
Our studies on the biochemical and genetic basis of bioactivities provide a multi-component, systems biology approach to dosage of these medicines, maximizing complex therapeutic effects while minimizing harmful side effects. This challenge requires new technology being developed with CSBi for data generation, data management and modeling.
Determining genetic diversity through single nucleotide polymorphisms
Analysis of single nucleotide polymorphisms (SNP) single base changes in DNA sequence that distinguish one individual tree from another enabled us to identify Tongkat Ali trees that came from different geographical regions. In coordination with their component profiles, we can identify the particular trees which produce the most important biologically-active agents. This information then permits the selection of highly productive trees for propagation and genetic engineering of the species with the highest potential productivity and benefit.
Understanding the overall effects of these compounds on biological systems
Research in the Rha lab also centers around the biological activities that these compounds have on mammalian systems. The response of genes in mammalian cell lines to such compounds are described by transcriptional profiling. By looking at the regulation of genes on a genome-wide scale, we can probe the system-wide response to these natural products. By providing this understanding of the overall mechanism of action of these compounds, systems biology helps us to better recognize potential medicinal significance and applications.
- Guillouet, J. H. Choi, C. K. Rha and A. J. Sinskey (1999). Effects of yeast extract on the production and the quality of the exopolysaccharide, zooglan, produced by Zoogloea ramigera 115SLR, Appl. Microbiol. Biotechnol. 51:235-240.
- Sang, J.S., K.D. Snell, B.W. Kim, C.K. Rha, and A.J. Sinskey (2001). Increased poly-b-hydroxybutyrate (PHB) chain length by the modulation of PHA synthase activity in recombinant Escherichia coli. Biotechnol. Lett. 23:2057-2061.
- Osman, A., Jordan, B., Lessard, P.A., Muhammad, N., Haron, M.R., Riffin, N.M., Sinskey, A.J., Rha, C.K., and D.E. Housman (2003). Genetic diversity of Eurycoma longifolia inferred from single nucleotide polymorphisms. Plant Physiology 131(3):1294-301.
- Fry, R.C., T.G. Sambandan & C.K. Rha (2003). DNA damage and stress transcripts in prematurely aging yeast mutant sgs1. Mechanisms of Ageing and Development 124:839-846.
- Coldren, C.D., P. Hashim, J.M. Ali, S.K. Oh, A.J. Sinskey & C.K. Rha (2003). Gene expression changes in the human fibroblast induced by Centella asiatica triterpenoids. Planta Medica 69: 725-732.
- Gorret, N., S.K. bin Rosli, S.F. Oppenheim, L.B. Willis, P.A. Lessard, C. Rha, and A.J. Sinskey. (2004) Bioreactor culture of oil palm (Elaeis guineensis) and effects of nitrogen source, inoculum size, and conditioned medium on biomass production. J. Biotechnol. 108:253-263.
- Lawrence, A.G., J. Choi, C. Rha, J. Stubbe, and A.J. Sinskey. (2005) In vitro analysis of the chain termination reaction in the synthesis of poly-(R)-b-hydroxybutyrate by the Class III synthase from Allochromatium vinosum. Biomacromolecules, 6 (4), 2113 -2119.
- Kurosawa K., Bui. V.P., VanEssendelft J. L., Willis L.B., Lessard P.A., Ghiviriga I., Sambandan T.G., Rha C.K., Sinskey A.J. (2005) Characterization of Streptomyces MITKK-103, a newly isolated actinomycin X2-producer. Applied Microbiology and Biotechnology, Dec 2005, Pages 1-10.