About Me

Work Experiences

PhD Thesis

Resumes

 

Chuang-Chung (Justin) Lee

 

Department of Chemical Engineering, Massachusetts Institute of Technology

Email: chchlee@alum.mit.edu

Web: web.mit.edu/mcraegroup/ChuangChuang.html

Tel: 781-577-6383 (O)

Address: 230 Third Avenue, 5th Floor, Waltham, MA, 02451

Education:

§         Ph.D. Massachusetts Institute of Technology, 2008

§         M.S. Massachusetts Institute of Technology, 2005

§         B.S. National Taiwan University, 2001

 

Research Interests:

§         Kinetics of Amyloid Fibrillation

 

Claimed to be the number one cause of senile dementia, Alzheimer’s disease is one of the disorders that involve misfolding of amyloid protein and formation of insoluble fibrils.  Although a variety of time dependent fibrillation data in vitro are available, few mechanistic models have been developed.  To bridge this gap we used chemical engineering concepts

 

from polymer dynamics, particle mechanics and population balance models to develop a mathematical formulation of amyloid growth dynamics.  A three-stage mechanism consisting of natural protein misfolding, nucleation, and fibril elongation phases was proposed to capture the features of homogeneous fibrillation responses.  In addition, the proposed mechanism reflects the effect of each factor on fibril formation kinetics such as protein types, initial concentration, seeding, and agitation over a series of experimental conditions.  While our cooperative laboratory provided us with experimental findings, we guided them with experimental design based on modeling work.  It was through the iterative process that the size of fibril nuclei and concentration profiles of soluble proteins were elucidated.  The study also reveals further experiments for diagnosing the evolution of amyloid coagulation and probing desired properties of potential fibrillation inhibitors.

§         Short-term Plasticity

 

Depending on the types, synapses tend to depress or facilitate under repetitive stimuli.  There were models and hypotheses describing individual reactions yet few physiology-based models have been developed systematically to describe what and how key factors influence synaptic strength.  In this paper, calcium dynamics at presynapse were considered in describing the release of glutamates as neurotransmitters; at postsynapse, binding of glutamate to AMPA receptor was modeled as a first order delay system that outputs excitatory current.  Since the model was kept mathematically tractable, the analytical solution to the resonance frequency, which is the most crucial determinant of plasticity tendency, could be derived. 

 

This unified model together with the closed form solution is broadly supported by transient and frequency experimental data. Responses from both depressing synapse and facilitating synapse can be explained by the model.  Based on the results of parameter estimation, high initial release probability and low recovery rate cause depression, which coincides with the vesicle depletion hypothesis.  Furthermore, we were able to pinpoint the parameters influential to the resonance frequency.  High calcium initial concentration and gain of calcium current to concentration result into high initial release probability and thus lower resonance frequency.  In contrast, for synapses less sensitive to calcium or with higher recovery rate, high frequency stimuli are required to get them saturated, so higher resonance frequency and thus facilitation are observed.  Based on the model, experimental schemes were also suggested to switch the synapses from depression to facilitation or vice versa.

§         Long-term Plasticity

 

The accumulation of amyloid fibrils is suspected to cause abnormal modification of long-term synaptic plasticity which is viewed as the principal mechanism underlying learning and memory.  Most synapses show long-term potentiation (LTP) or depression (LTD) which can last for more than hours after tetanus stimuli are applied and removed.  Even though there are hypotheses explaining individual experimental findings, few systematic models have been built to specify the actual mechanism contributing to long lasting change.  Therefore, we first considered vesicle trafficking in presynapse to describe the release of glutamate as neurotransmitter.  Then in the postsynaptic compartment, we developed a calcium entrapment model to simulate the excitatory current and voltage.  The systematic model consists of equivalent electrical circuits as well as ligand- and voltage-gated NMDA receptors.  This built model is supported by a broad range

 

of experimental measurements.  According to the result of model differentiation, we confirmed that calcium entrapment model explains graded response of synaptic LTP better than biostability mechanism.  In the mean time, we are beginning to analyze new experimental data to assess the influence of amyloid fibrils on the regulation of long term potentiation. 

 

Publications:

§         Journal Papers

Lee, C.-C., Poon, C.-S., and McRae, G. J. (2009) “The Unified Theory of Spike Timing Dependent Plasticity”, J. Neurosci., in preparation.

Lee, C.-C., Anton, M., Poon, C.-S., and McRae G. J. (2008) “The Unified Theory of Homosynaptic Short Term Depression and Facilitation”, J. Comut. Neurosci.  In print, DOI 10.1007/s10827-008-0122-6.  Abstract  |  Full Text

Lee, C.-C., Nayak, A., Belfort, G., and McRae, G. J. (2007) “A Three-Stage Kinetic Model of Amyloid Fibrillation”, Biophys. J., 92(10):3448-3458.  Abstract  |  Full Text

Chien, W.-C., Lee, C.-C., and Tai, C. Y. (2007) “Heterogeneous Nucleation Rate of Calcium Carbonate Derived from Induction Period”, Ind. Eng. Chem. Res., 46(20):6435-6441.  Abstract  |  Full Text

Tai, C. Y., Chien, W.-C., Hsu, J.-P., and Lee, C.-C. (2001) “Supersaturation, Induction Period, and Metastable Zone Width of Calcium Carbonate System”, Chem. Eng. Comm., 188:243-263.  Abstract  |  Full Text

§         Conference Abstracts

Nayak, A., Lee, C.-C., McRae, G. J., and Belfort, G. (2007) “Fibrillation Kinetics of Recombinant Human Insulin with Osmolytes: Experiments and Kinetic Modeling”, ACS Colloid & Surface Science Symposium in Newark, DE.  Abstract

Sorci, M, Nayak, A., Lee, C.-C., McRae, G. J., and Belfort, G. (2007) “Memory And Reversibility of Insulin Oligomers”, SBE's International Conference on Biomolecular Engineering in Coronado Island, CA.  Abstract

Lee, C.-C., Nayak, A., Belfort, G., and McRae, G. J. (2006) “A Mathematical Model of Amyloid Fibrillation: The Case for Insulin”, Biophysical Society Conference in SLC, UT.  Abstract

Nayak, A., Dutta, A., Lee, C.-C., McRae, G. J., and Belfort, G. (2006) “Insulin Fibrillation Kinetics at Interfaces”, AIChE annual meeting in SF, CA.  Abstract

 

Honors:

Member of Biophysical Society, 2006-2007

MIT Class of 1936 Fellowship, 2003

Honorary member of of the Phi Tau Phi Scholastic Honor Society, 2001

Lee Yuan Tze Scholarship for Chemistry, 2000

Yen Family Scholarship,1998-1999