Kyongbum Lee
Assistant Professor
Chemical and Biological Engineering
4 Colby Street, Room 142
Medford, MA 02155
617-627-4323

Education:
2002 - Post-doc, Massachusetts General Hospital
2002 - Ph.D., M.I.T., Cambridge, MA
1995 - B.S., Stanford University, Stanford, CA

Research Areas:

Interest areas: systems biology, metabolic engineering, and tissue engineering

Our research is ultimately aimed at better understanding the chemical design of living systems through the development and application of analytical platforms, modeling tools, and other enabling technologies. We are especially interested in characterizing and manipulating cellular metabolism for a variety of basic and applied studies. Central to these studies is the notion that many specialized cellular functions critically interact with cellular metabolism, which in turn is accomplished by the concerted actions of a network of biochemical reactions. In this light, the cell is viewed as a complex system whose biochemical functions cannot be simply attributed to the actions of one or a few molecules; rather, the functions result from the many direct and indirect interactions between genes, enzymes, and metabolites. Therefore, a systems-oriented approach is warranted. Our research is also motivated by the growing national need to find and evaluate new therapies for obesity and type 2 diabetes.

Systems Biology - There is increasing evidence that the functions and structural features of a biochemical network are intertwined. Thus, a useful approach to studying the design of these complex systems has been to characterize their layout, or ‘wiring.’ Earlier topological studies using graph theoretical models have shown that many biological networks are “scale-free,” and share the “small-world” property. In addition to these global properties, recent studies have also examined sub-structures (‘modules’) that arise from local interactions between the network’s components. To date, these modules have been typically characterized assuming that the distribution of (enzyme-mediated) connections is a fixed property of the network. Little work has been done to investigate how the modular organization of a biochemical network may vary with the extents of its chemical interactions, or ‘connection strengths.’ Work in our laboratory has been aimed at developing a modeling framework to integrate the analysis of the structural and functional layout of biochemical networks. For example, we have very recently developed and applied a series of algorithms for the rational decomposition of metabolic networks based on experimentally-derived reaction activity data.

Modular decomposition of the adipocyte metabolic network

Metabolic Engineering - This area of our research uses mathematical models of metabolic pathways in conjunction with experimental biochemistry techniques to quantitatively study the metabolic basis of adipose tissue development and growth. As a chronic condition, obesity increases the risk for many diseases and disorders, including diabetes, cardiovascular disease, and some forms of cancer. Solid epidemiological data support the pivotal role of body fat (white adipose tissue, WAT) mass in the development of the obesity-related risk factors. In addition to fundamental insights into adipocyte metabolic regulation, we seek to obtain; (1) novel drug targets, for example enzymes that catalyze the key controlling steps in adipocyte lipid accumulation; and (2) robust, sensitive, and easily measured metabolite biomarkers for diagnosis of obesity-related diseases and efficacy assessment of therapeutics. To these ends, we have performed in silico and in vitro studies characterizing the metabolic flux profiles of de novo adipocyte formation, identified target pathways for metabolic intervention, and demonstrated the feasibility of achieving a global shift in lipid accumulation through the forced expression of a single protein.

Tissue Engineering - In our research, tissue engineering tools are used to design, build, and optimize model systems whereby important cellular functions may be studied under well-controlled conditions while maintaining a high degree of physiological relevance. The primary focus here is on engineering the cellular component and its medium (as opposed to the materials or reactor housing). Current projects leverage developments in micro-fluidics and stem cell biology to generate flow-through incubators that afford spatial control over the chemical environment of the cultured cells. This incubator is used for a number of on-going studies involving heterogeneous cell components (e.g., adipocyte-preadipocyte co-culture) and solution gradients of exogenously added chemicals (e.g., drug transformation by hepatocytes).

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Recent Publications:

Books & Reviews

Lee, K. and Kaplan, D.L., "Tissue Engineering II: Basics of Tissue Engineering and Tissue Applications," in Advances in Biochemical Engineering/Biotechnology, vol. 103, T. Scheper, Ed. Heidelberg: Springer Verlag, 2006.

Lee, K. and Kaplan, D.L., "Tissue Engineering I: Scaffold Systems for Tissue Engineering," in Advances in Biochemical Engineering/Biotechnology, vol. 102, T. Scheper, Ed. Heidelberg: Springer Verlag, 2006.

Koffas, M., Roberge, C., Lee, K., and Stephanopoulos, G., "Metabolic engineering," Annu Rev Biomed Eng, 1, pp. 535-57, 1999.

Lee, K., Berthiaume, F., Stephanopoulos, G.N., and Yarmush, M.L., "Metabolic flux analysis: a powerful tool for monitoring tissue function," Tissue Eng, 5, pp. 347-68, 1999.

Accepted/In Press

ADDIN EN.REFLIST Si, Y., Yoon, J., and Lee, K., "Flux profile and modularity analysis of time-dependent metabolic changes of de novo adipocyte formation," Am J Physiol Endocrinol Metab, in press, 2007.

Recent Publications

ADDIN EN.REFLIST Si, Y., Palani, S., Jayaraman, A., and Lee, K., "Effects of forced uncoupling protein 1 expression in 3T3-l1 cells on mitochondrial function and lipid metabolism," J. Lipid Res., pp. M600343-JLR200, 2007.

Yoon, J. and Lee, K., "Metabolic flux profiling of reaction modules in liver drug transformation," Pac Symp Biocomput, 12, pp. 193-204, 2007.

Abraham, L.C., Dice, J.F., Finn, P.F., Mesires, N.T., Lee, K., and Kaplan, D.L., "Extracellular matrix remodeling-Methods to quantify cell-matrix interactions," Biomaterials, 28, pp. 151-61, 2007.

Nolan, R.P., Fenley, A.P., and Lee, K., "Identification of distributed metabolic objectives in the hypermetabolic liver by flux and energy balance analysis," Metab Eng, 8, pp. 30-45, 2006.

Yoon, J., Blumer, A., and Lee, K., "An algorithm for modularity analysis of directed and weighted biological networks based on edge-betweenness centrality," Bioinformatics, 22, pp. 3106-8, 2006.

Jayaraman, A., Roberts, K.A., Yoon, J., Yarmush, D.M., Duan, X., Lee, K., and Yarmush, M.L., "Identification of neutrophil gelatinase-associated lipocalin (NGAL) as a discriminatory marker of the hepatocyte-secreted protein response to IL-1beta: a proteomic analysis," Biotechnol Bioeng, 91, pp. 502-15, 2005.

Lee, K., Hwang, D., Yokoyama, T., Stephanopoulos, G., Stephanopoulos, G.N., and Yarmush, M.L., "Identification of optimal classification functions for biological sample and state discrimination from metabolic profiling data," Bioinformatics, 20, pp. 959-69, 2004.

Lee, K., Berthiaume, F., Stephanopoulos, G.N., and Yarmush, M.L., "Induction of a hypermetabolic state in cultured hepatocytes by glucagon and H2O2," Metab Eng, 5, pp. 221-9, 2003.

Lee, K., Berthiaume, F., Stephanopoulos, G.N., and Yarmush, M.L., "Profiling of dynamic changes in hypermetabolic livers," Biotechnol Bioeng, 83, pp. 400-15, 2003.

Chan, C., Berthiaume, F., Lee, K., and Yarmush, M.L., "Metabolic flux analysis of hepatocyte function in hormone- and amino acid-supplemented plasma," Metab Eng, 5, pp. 1-15, 2003.

Chan, C., Berthiaume, F., Lee, K., and Yarmush, M.L., "Metabolic flux analysis of cultured hepatocytes exposed to plasma," Biotechnol Bioeng, 81, pp. 33-49, 2003.

Arai, K., Lee, K., Berthiaume, F., Tompkins, R.G., and Yarmush, M.L., "Intrahepatic amino acid and glucose metabolism in a D-galactosamine-induced rat liver failure model," Hepatology, 34, pp. 360-71, 2001.

Lee, K., Berthiaume, F., Stephanopoulos, G.N., Yarmush, D.M., and Yarmush, M.L., "Metabolic flux analysis of postburn hepatic hypermetabolism," Metab Eng, 2, pp. 312-27, 2000.

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People:

Current Members

• Yaguang Si
  B.S., Biology, Fudan University, Shanghai, China
   
• Jeong-Ah Yoon
  B.S., Pusan National University, Busan, South Korea
  M.S., POSTECH, Pohang, South Korea
   
• Hai Shi
  B.S., Zhejiang University, HangZhou, China
  M.S., Zhejiang University, HangZhou, China
   
• Kyle McElearney
  B.S., Worcester Polytechnic Institute, Worcester, MA
   
• Ning Lai
  B.S., Beijing University of Chemical Technology, China
   
• Andrew Fraser
  B.S., Mechanical Engineering, Tufts University (expected 2006)

• Andrew Fenley
  M.S., Chemical Engineering, 2004 - currently at National Instruments
   
• Roshni Patel
  M.S., Biotechnology Engineering, 2004 - currently pursuing a Ph.D. at Brown University, Center for Biomedical Engineering
   
• Ryan Nolan
  M.S., Chemical Engineering, 2005 - currently at Wyeth Pharmaceuticals, MA
   
• Anura Patil
  B.S., Chemical Engineering, 2006 - currently at Johnson & Johnson, NJ

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Positions:

We are currently looking for a part-time (summer 2007) undergraduate research assistant to work in the areas of metabolic engineering and/or tissue engineering A background in chemical or biochemical engineering is preferred, but other related majors will also be considered. For more information, please contact: kyongbum.lee@tufts.edu with a brief resume.

News & Other Info:

• AP Feature on Professor Kyongbum Lee's Obesity Research
   
• Congratulations to Jeongah for the Graduate Award for Outstanding Graduate Research in Engineering!
  
  
• Call for papers:
  • BMES Annual Meeting, Los Angeles, CA, Sep. 26-29, 2007
    Abstract submission is now open for the upcoming Biomedical Engineering Society (BMES) meeting. We invite abstracts to a session on Regulation and Pathophysiology of Metabolic Networks. This session is part of a track on Systems Biology and Bioinformatics. Topics include the quantitative analysis of metabolic networks coupled to regulatory architectures, the sensitivity of organism-scale metabolic networks to pathological and pharmacological perturbations. Find out more information on submission process and deadlines >>
    
    
  • AIChE Annual Fall Meeting, Salt Lake City, UT, Nov. 4 -9, 2007
    Abstract submission is now open for the upcoming American Institute of Chemical Engineers (AIChE) meeting. We invite abstracts to a session on Proteomics & Metabolomic Approaches to Systems Biology. This session is part of a Topical Conference on Systems Biology.
    
    
  • We also invite abstracts to a session on Genomics and Proteomics for Tissues and Organs. We seek presentations that utilize experimental methods, computational modeling, and integrated experimental and computational approaches for the systematic analysis of tissues and organ systems. Topics of interest include, but are not limited to: characterization of gene and protein networks in the context of disease states, novel technologies for monitoring expression profiling, and study of gene and protein expression dynamics. Multi-scale approaches involving measurement and regulation across gene, protein, and metabolic systems are particularly encouraged. Find out more information on submission process and deadlines >>
    

• Chemical Reaction Engineering, CHBE 102
• Metabolic and Cellular Engineering, CHBE 167
• Advanced Kinetics and Reactor Engineering, CHBE 103/160
• Biological Engineering, EN 69