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Research Highlights

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Research Highlights

Molecular Genetics Lab – PI: Dr. Yun-Liang Yang

  • Discovering that drug resistance and morphogenesis/virulence both are under the regulation of Efg1 and Cph1, two known virulence factors in Candida albicans.
  • Unveil the involvement of glycolytic enzymes in the morphogenesis/virulence pathway.
  • Identification of the first anti-dengue drugs in cell culture system.

 

Lab – PI: Dr. Yun-Ming Wang

  • 2007 Joint Annual Meeting ISMRM (International Society for Magnetic Resonance in Medicine)-ESMRMB (European Society for Magnetic Resonance in Medicine and Biology) 2007 Poster Award 3rd place

YMWang-01

  • Synthesis, Complexation and Water Exchange Properties of Gd(III)–TTDA–Mono and Bis(amide) Derivatives and Their Binding Affinity to Human Serum Albumin, Dalton Trans., 2749-2759, 2007. (Selected as Journal Cover)
    With the objective of tuning the lipophilicity of ligands and maintaining the neutrality and stability of Gd(III) chelate, we designed and synthesized two bis(amide) derivatives of TTDA, TTDA-BMA and TTDA-BBA, and a mono(amide) derivative, TTDA-N-MOBA. The stability constants of TTDA-mono and bis(amide) complex are significantly lower than those of TTDA and DTPA, but the selectivity constants of these ligands for Gd(III) over Zn(II) and Cu(II) are slightly higher than those of TTDA and DTPA. From the 1H NMR titrations, the identification of the protonation site of the amide ligand shows that the first protonation site occurs on the central nitrogen atom. The simultaneous treatment of 17O NMR data is used to obtain many parameters affecting the proton relaxivity of Gd(III) complexes. It is found that the replacement of one carboxylate group by an amide group decreases the water-exchange rate of the gadolinium(III) complexes by a factor of about 5, and the trend is similar to those of DTPA and DTPA-bis(amide) derivatives. Furthermore, from the relaxivity and ultrafiltration studies, it is clear that the bound relaxivity (r1b) values of [Gd(TTDA-N-MOBA)(H2O)]/HSA and [Gd(TTDA-BBA)(H2O)]/HSA have remarkably high value. In addition, the increase of lipophilicity and non-covalent binding affinity with HSA of TTDA-mono and bis(amide) Gd(III) chelates increases the association constants for the binding of Gd(III) chelates to HSA.
  • Synthesis and Characterization of a New Bio-activated Paramagnetic Gadolinium(III) Complex [Gd(DOTA-FPG)(H2O)] for Tracing Gene Expression, Bioconjugate Chem. 18, 1716-1727, 2007. (Selected as Journal cover)
    A smart contrast agent for magnetic resonance imaging (MRI) can be used to exploit an enzymatic activity specific to the tissue or disease state signified by converting an MRI-inactivated agent to an activated MRI agent. In this study, a ß-galactopyranose-containing gadolinium(III) complex [Gd(DOTA-FPG)(H2O)] was designed, synthesized and characterized as being potentially suitable for a bio-activated MRI contrast agent. The rotational correlation time value of [Gd(DOTA-FPG)(H2O)] is dramatically longer than that of [Gd(DOTA)(H2O)]. Relaxometric studies show that the percentage change in the T1 value of [Gd(DOTA-FPG)(H2O)] decreases dramatically in the presence of ß-galactosidase and human serum albumin. 

YMWang-02

  • The signal intensity of the MR image for [Gd(DOTA-FPG)(H2O)] in the presence of human serum albumin and ß-galactosidase (2670 ±210) is significantly higher than that of [Gd(DOTA-FPG)(H2O)] in the sodium phosphate buffer solution (1490 ± 160). In addition, the MR images show a higher intense enhancement in CT26/ß-gal tumor with ß-galactosidase gene expression but not for the CT26 tumor without ß-galactosidase gene expression. 
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YMWang-03


 
  • Molecular mechanism study of Mst3-mediated cell apoptosis
    Mst3 was found to be present in the mitochondrial intermembrane space, where it may associate with pro-apoptotic proteins, AIF and endonuclease G (EndoG). In mitochondria, Mst3 was postulated to regulate the activity of pro-apoptotic proteins and/or the associated DNase in response to the apoptotic stimuli, such as oxidative stress and staurosporine.  

CJYuang-01

Fig. 1 The endogenous Mst3 (thread-like green fluorescence) was found to partially colocalize with Mitotracker (red), a mitochondrial specific fluorescent dye, and red fluorescent signals of AIF and EndoG (yellow/orange signal).
 
 
 
    
  • Elucidate the role of Mst3 in normal spontaneous delivery
    We demonstrated for the first time that Mst3 plays an essential role in the apoptosis of trophoblasts during normal spontaneous delivery. Oxidative stress, but not hormones released during labor such as prostaglandin E1, oxytocin or angiotensin II, induces the expression of Mst3 and apoptosis of human term placenta during labor (Fig. 2). Further studies showed that Jun N-terminal kinase (JNK) may participate in the signaling pathway of H2O2-induced apoptosis by mediating the level of Mst3.

CJYuang-02

Fig. 2. Human tissue specimens were placenta from spontaneous delivery (a-d), selective Cesarean section (e-h) and fetal membrane of first trimester (i-l). Mst3 expression (a,e,i); apoptosis signals (b,f,j); nitrotyrosine (c,g,k) and caspase3 activations (d,h,l were indicated).
 
 
 
    
  • Development of bio-nanodevices for cancer therapy
    An novel horseradish peroxidase (HRP)-encapsulated silica nanoparticles (HRP-SNP) was developed in our laboratory with an average size of around 100 nm for the application of cancer therapy (Fig. 3). HRP was demonstrated to catalyze the conversion of non-toxic prodrug indole-3-acetic acid (IAA) into toxic products for cancer therapy. Further studies showed that the developed HRP-SNP was nontoxic to HeLa cells without IAA; whereas, in the presence of IAA, the viability of HeLa cells decreased rapidly in a time- and dosage-dependent manner.

 

CJYuang-03 


HLPeng


 
  • Self-assembled molecular magnets on patterned silicon substrates: Bridging bio-molecules with nanoelectronics 
    The paper reports the methods of preparing molecular magnets and patterning of the molecules on a semiconductor surface. A highly magnetically aligned metallothionein containing Mn and Cd (Mn,Cd-MT-2) is first synthesized, and the molecules are then placed into nanopores prepared on silicon (0 0 1) surfaces using electron beam lithography and reactive ion-etching techniques. We have observed the self-assemble growth of the MT molecules on the patterned Si surface such that the MT molecules have grown into rod or ring type three dimensional nanostructures, depending on the patterned nanostructures on the surface. We also provide scanning electron microscopy, atomic force microscopy, and magnetic force microscope studies of the molecular nanostructures. This engineered molecule shows molecular magnetization and is biocompatible with conventional semiconductors. These features make Mn,Cd-MT-2 a good candidate for biological applications and sensing sources of new nanodevices. Using molecular self-assembly and topographical patterning of the semiconductor substrate, we can close the gap between bio-molecules and nanoelectronics built into the semiconductor chip.
 

CCChang-01

 

  • Laser induced popcornlike conformational transition of nanodiamond as a nanoknife
    Nanodiamond (ND) is surrounded by layers of graphite on its surface. This unique structure feature creates unusual fluorescence spectra, which can be used as an indicator to monitor its surface modification. Meanwhile, the impurity, nitroso (C-N=O) inside the ND can be photolyzed by two-photon absorption, releasing NO to facilitate the formation of a sp3 diamond structure in the core of ND and transforming it into a sp2 graphite structure. Such a conformational transition enlarges the size of ND from 8 nm into 90 nm, resulting in a popcorn-like structure. This transition reaction may be useful as nano-knives in biomedical application.

    1. SEM images of the A549 cell lines, irradiated with/without laser following ND treatment.
    2. SEM image of 6 nm nano-diamond before and after laser radiated. The average size of laser radiated nano-diamond is about 90 nm.

CCChang-02


 

Molecular Anticancer Lab – PI: Dr. Jui-I Chao

  • In recent five years, our projects focused on exploring the role and regulation of survivin in human cancer cells. My laboratory has contributed several novel findings on the roles of survivin to the academic world and further applications. Besides, we investigated potential anticancer drugs from Chinese herbs, flavonoids, and novel synthetic agents. In addition, our team has achieved some pioneering works studying nanodiamond (ND) for bio-applications. Overall, we have contributed high impact findings on survivin and nanodiamond to the academic world and further applications. 
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  • Immunology: Our research has indicated that the virulent molecule— Hsp60 of H. pylori was one of the major protein to inhibit the immunity of host. And we further test the effect of the Hsp60 on other tissue cells.
  • Liposome: We have established the novel liposome's structure and producing procedure. Furthermore, we will deeply research the mechanism of its stably and quickly adsorptive function. Simultaneously, we will package the drug into this liposome and combine the targeting molecule to achieve specific drug delivery.
  • Production of antibody and protein engineering: We have established the chimeric protein which combined a portion of VEGF and IgG Fc. Further, we used this chimeric protein to treat the tumor cell and this kind therapeutical method could efficiently inhibit the tumor growth.


  • We used pluripotent P19 cells to study the function of microtubule-associated proteins during neuritogenesis. Multi-dimensional protein identification technology (one type of gel-free high throughput proteomics) was performed on microtubule-associated proteins prepared before versus shortly after neurite induction. More than 800 proteins were consistently identified in both proteomes. Surprisingly, when these two proteomes were quantitatively compared, the majority of the proteome remain unchanged. Substantial changes in the microtubule-associated proteome occurred at the level of individual proteins. Based on our proteomic results, we assayed primary neurons using RNA interference to identify a novel inhibitory role for protein TRIM2 in neurite elongation.
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EHuang-01


Last Edited by : 2014-12-12 23:55:19
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