Paper Recommended

This time I would like to recommend two articles.  One of them is stem cell in mouse model, the other is about tissue engineering in curing patient.

 

1. Generation of a prostate from a single adult stem cell. Kevin G. Leong, Bu-Er Wang, Leisa Johnson and Wei-Qiang Gao. Nature, 2008, Vol 456, page 804.

2. Clinical transplantation of a tissue-engineered airway. Paolo Macchiarini, Philipp Jungebluth, Tetsuhiko Go, M Adelaide Asnaghi, et al. Lancet, 2008, Vol 372, page 2023.

The reason I put these two articles is that I strongly believe high quality basic research in biomedicine will eventually benefit clinic. 

 

The first paper is from Genentech, which is a company, which is a little bit surprising because people still don’t believe that industrial can conduct high quality basic research.  Simply by reading the title we can have an idea of the article.  The authors isolate prostate stem cells (lin^–Sca-1⁺CD133⁺CD44⁺CD117⁺) from mouse prostate and transplant a single prostate stem cell into the other mouse and a generate functional, secretion-producing prostates developed.  This article showed the powerfulness of stem cell, not even embryonic stem cell, but just prostate stem cell.

The second article is the fantastic application of tissue engineering in clinical: removal of cells and MHC from a human donor trachea, growth of the recipient’s epithelial cells and mesenchymal stem-cell-derived chondrocytes on this trachea and finally replace the recipient’s failed trachea with this graft.  It seemed easy but it is technically challenging.  This is a example that technology saved patient’s life, again.

 

The figure shows volume-rendering CT (A and C), and virtual bronchoscopic (B and D) reconstructions before (A and B) and 1 month after (C and D) engraftment of tissue-engineered trachea to replace left main bronchus.

Paper recommend (11)

—-I guess t_carpediem might be interested in this issue.

 

    In this issue of Nature there are 2 papers and 1 view talking about cancer therapy based on knowing which signal pathways was aberrantly turned on or off. The key information is: newly developed anti-cancer drugs usually target a specific signaling pathway or a single component of a signaling pathway, therefore before we choose drug or drug combination we need to know which signaling pathway is not “normal”. And their data showed a good correlation between drug response and gene expression signature/signaling pathway information. These 2 papers represent a very good example of bi-directional research: back and force between bench work and bedside application.

 

1. Signatures guide drug choice. Nature, 2006, Vol.439, 274.

2. Oncogenic pathway signatures in human cancers as a guide to targeted therapies. Nature, 2006, Vol.439, 353.

3. BRAF nutation predicts sensitivity to MEK inhibition. Nature, 2006, Vol.439, 358.

Paper recommend (10)

1.  Unidirectional molecular motor on a gold surface. Nature, 2005, Vol.437, 1337.

The reason I recommend this paper is that I did a proposal in Purdue, in which a multi-state reversible molecular motor was proposed, also using UV or heat to control the states. One of the advantage of this design is that the rotor can rotate in both direction. And also the S-S-Au interaction me it potentially reversible (although S-S-Au is widely used).

 

2.  Multistep synthesis of a radiolabeled imaging probe using integrated microfluidics. Science, 2005, Vol. 310, 1793

This idea of synthesis by microfluidics is so COOL! You must read it.

Continuous-flow microreactors are newly (2002) used on chemical synthesis, whose advantages include enhanced heat transfer performance, faster diffusion and reaction kinetics, and improved product selectivity. The authors designed a 5-step reaction circuit. The first figure is the reaction circuit. I think the control of solvent and substrate fluid is quite important. Two important techniques are used: (1) in situ ion exchange column was combined with a rotary pump to concentrate substrate; (2) gas-permeable poly(dimethylsiloxane)(PDMS) matrix allows solvent exchange to occur within the microfluid channel through direct evaporation, thereby allowing for the sequential execution of chemical reactions in PDMS-compatible solvents.

 

3.  The widespread impact of mammalian microRNAs on mRNA repression and evolution. Science, 2005, Vol 310, 1817

MicroRNA are so hot these days. More and more function of microRNA are discovered. I think the first 3 scientists (one of them is in Dartmouth Medical School) discovering microRNA will get Nobel Prize.

Presentation

A good scientist may not be a good presenter; however, presentation is so important to scientists. These days I am thinking of the issue of presentation.

 

Last month my boss gave a presentation in a small conference. Throughout his presentation he was emphasizing two points: first, team work; second, bidirectional work back and forth between bench and bedside work. He did not show much data but each figure shown supported a key point. Two weeks ago there was an annual “Dartmouth Life Science Symposium” and I attended part of it. The symposium was held in a large hall and there were at least 300 people from different fields of Bio-Med research in Dartmouth. A professor from Harvard Medical School gave us a talk on her work. I did not fully understand it, but I guess the work should be excellent otherwise Dartmouth would not have invited her. The problem is that she showed too much data too quickly for the audience to understand her if not in a close field. The next talk on prion was given by a professor from Biochemistry Department of Dartmouth Medical School. On the contrary he showed very little data but make his point very clear so I think most of the audience could obtain enough information.

 

So here is my point: data is very important to a presentation but overwhelming data could also be confusing. Some scientists tend to show as many data as possible to let audience know their work is really good. But the problem is, unless the audience work in a very close field, overwhelming data can only be confusing and boring. A good presenter should present a whole tree (his/her concept, idea or project) and use data (leaves) to support it.

 

Next Monday I will present in our lab meeting, I will try my point.

 

Aknowledgement: I thank birdfreehzh for thoughtful ideas and discussion.

Paper recommend (9)

1. Reaction pathways leading to arylene ethynylene macrocycles via alkyne metathesis. J. Am. Chem. Soc., 2005, 127, 11863.

    Prof. Moore is a big guy. In this article they demonstrated that the macrocycle formation is thermodynamically rather than kinetically controlled. This paper is not so excited on synthesis or the function of the product, but I guess the product can be potentically used to construct nano structure.

 

2. Cell penetrating agents based on a polyproline helix scaffold. J. Am. Chem. Soc., 2005, 127, 11863.

    The author, Prof. Chmielewski, is a smart and tough woman in Purdue Univ. I listened to her seminar. One thing is that she was promoted to professor earlier than her husband, who is also a professor in organic chemistry in the same department. Although she got PhD in organic synthesis many years ago her interested is in chemical biology: how to make molecules to probe bio-function. You can see that her synthesis is not so difficult but the most important is the molecules have some useful bio-function.

Paper recommend (8)

  I was so busy that the paper recommend update is a little slow. I put two reviews and a perspective as well as three original articles because I think the reviews are cool and the perspective can lead us to think more.

1. Genes that mediate breast cancer metastasis to lung. Nature, 2005, 436, 518.

  The authors are in Memorial Sloan-Kettering Cancer Center (MSKCC), which is a top 3 cancer center in USA. This article presents an excellent example on cancer research: generate cell line, gene expression microarray, animal model and clinical data. I always think that cancer research is not only basic science or clinical application, successful cancer research should from bench work to clinical research in a back-and-forth manner, this is why MSKCC is so successful. If we just look at any part of this article, we might find it not so exciting, but the whole project is exciting.

 

2. Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis. Nature, 2005, 436, 725.

3. Oncogene-induced senescence as an initial barrier in lymphoma development. Nature, 2005, 436, 660.

  The function of a specific gene is far more complicated than people originally thought. These two articles are good examples.

 

4. Pharmacogenetics-based therapeutic recommendations—-ready for clinical practice? NatureReviews Drug Discovery, 2005, 4, 639.

  People from academia and industrial often talked about the possibility of treat different patients with same diseases by differents drugs according to their different genomic information. This perspective gives us a good view.

 

5. Asymmetry on large scale: the roadmap to stereoselective processes. NatureReviews Drug Discovery, 2005, 4, 685.

  Synthetic organic chemists made great effort to discover and improve asymmetric reaction, but drug industy is different. Not all excellent asymmetric reactions can be used on industry, this review gives us a good view of industrial asymmetric synthesis.

 

6. The convergenc of synthetic organic and polymer chemistries. Science, 2005, 306, 1200.

  Organic synthesis is the most important base of polymer chemistry, but polymer synthesis is different from classical organic synthesis. This review is worth reading.

Paper recommend (7)

1. A substrate-specific inhibitor of protein translocation into the endoplasmic reticulum. Nature, 2005, 436, 285.

2. Selective inhibition of contranslational translocation of vascular cell adhesion molecule 1. Nature, 2005, 436, 290

To my surprise, the above two papers desiened and synthesize very SIMILAR molecules to inhibit similar process: translocation of newly synthesized protein. I am not sure the two papers have any cooperation, or due to the excellent Medicinal Chemistry design, the targeted enzyme should have similar inhibitor. Both inhibitors are cyclic peptide-like molecules, which I preferrd in one of my homework of drug design in Purdue. It is interesting to compare the two papers.

 

3. A role for cell-cycle-regulated histone H3 lysine 56 acetylation in the DNA damage response. Nature, 2005, 436, 294

It is important to know the process of DNA repari, and acetylation of H3 is a hot point of research field.

Paper recommend (6)

1. Stem cell division is regulated by the microRNA pathway. Nature, 2005, 435, 974

I think the miRNA inhibite p21/p27/Dap pathway might be a more general pathway in control of cell cycle not only in stem cell.

 

2. DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis. Nature, 2005, 434, 864

This paper is highly related to my research. The authors prove that early in tumorigenesis human cells (from patients tissue) activate the ATR/Chk1 or/and ATM/Chk2-p53 pathway which result in apoptosis or cell cycle arrest. The authors also show that overexpression of oncogene can induce the same pathway in human cell. We are doing similar research on transgenic mice, wish could get some good result.

 

3. (1) A genetic screen for candidate tumor suppressors identifies REST. Cell, 2005, 121, 837. (2) A genetic screen identifies PITX1 as a suppressor of RAS activity and tumorigenicity. Cell, 2005, 121, 849

Tumor suppressor genes are always difficult to discover because those gene are lost or down-regulated in tumor. The above tow paper provide a good example in discovery of new tumor suppressor gene and how to obtain supportive data. The first is good because its screen method is good, the importance of the second one is the gene itself: it supress RAS.

 

Paper recommend (5)

1.    1.   An inhibitor of Bcl-2 family proteins induces regression of solid tumor. Nature, 2005, 435, 667.

This is a excellent example of drug design, bio assay and animal test. The used NMR to obtain proximal fragments and then link each fragments to achieve high-affinity binding, which may be better then crystal structure—computation. Another reason I trust this paper is that the in vivo data is available, which is absent in most paper. But all the data does not mean ABT-737, the compound, can be developed into real drug because clinical trial is tough.

 

2.     2.  “On Water”: unique reactivity of organic compounds in aqueous suspension. Angew. Chem. Int. Ed., 2005, 44, 3275.

I worked on organic reaction in aqueous solution for about 2 years and I fully understand that in most cases organic solvents is necessary to dissolve the reactants in the system. However, K. B. Sharpless gave me a surprise that dissolving is not required in his reaction. Water, avoided by most organic chemists, has some fantastic effect here.

(上一篇paper recommend其实早就写了, 忘了发)

Paper recommend (4)

1.    1.   A New Interpretation of the Baylis-Hillman Mechanism. J. Org. Chem., 2005, 70, 3980

There is a special reason that I put this paper: I used to work on Baylis-Hillman reaction for 3 month but made nothing out. I think Baylis-Hillman reaction might be one of the best organic name reaction in the past 20 years because it make three functional group together without damage the α,β-unsaturated ester. Another reason is that I am always glad to see a new mechanism of a excellent reaction.

2.    2.   Amplification of Acetylcholine-Binding Catenanes from Dynamic Combinatorial Libraries. Science, 2005, 308, 667

The beauty of this chemistry lies on the dynamically control in the synthesis. The fine design of this process is the key factor, which is quite different from traditional organic synthesis.

3.       A synthetic multicellular system for programmed pattern formation. Nature, 2005, 434, 1130.

Another excellent design! Although I cannot see the immediate application of this type of  multicellular system I still think engineering could make use of the biological system in a very different way.

 

Paper recommend (3): special issue

Causal Protein-Signaling Networks Derived from Multiparameter Single-Cell Data. Science, 2005, 308, 523-529

 

  This is a typical engineering paper rather than a biological one! The beauty of this paper is the totally new method to discover the network of signaling pathway. It is widely accepted that the signal transduction is not only many pathway but complicated network. The traditional methods investigate single pathway or protein-protein interactions, is “the blind men and the elephant” because they are not able to provide a systematic view. The authors said “the network is automatically constructed with no priories knowledge…”, which means were more background incorporated into the mathematic method, the more accurate network should be obtained. The Bayesian generated the signaling network from the multi-dimensional flow cytometry which detected the activation or inhibition of many protein in various conditions. I guess this is a much better use of flow cytometry data.

  However, the combination of Bayesian method and flow cytometry still has some technique difficulty: first, protein is not so easy to label as DNA; second, the knowledge of all protein should be enough to label them. And the most important is the method cannot find unknown signaling pathway.

  Despite the minor disadvantages and limits of the combination of Bayesian method and flow cytometry data, it is a very promising method to investigate signal transduction.

Paper recommend (2)

1. DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis. Nature, 2005, 434, 864 – 870

Good research in checkpoint in tumorgenesis!

 

2. Sheep retrovirus structural protein induces lung tumours. Nature, 2005, 434, 904 – 907

It is rare that viral Env protein could induce tumor and in this paper the authors provided evidence that immune recognition of Env can protect against JSRV tumorigenesis. Personally I think it necessary to investigate the detail molecular mechanism because the it could establish the network if immune system, protein and tumorgenesis, which is relatively poorly investigated. What’s more, the authors emphasize the difficulty and expense in experiment, which is also rarely mentioned in a paper.

 

3. Supramolecular chelation based on folding. J. Am. Chem. Soc., 2005, 127, 5928-5935.

It is cool but I need to think of its potential application (there must be).

 

paper recommend (1)

Harnessing Chaperones to Generate Small-Molecule Inhibitors of Amyloid ß Aggregation. Science, 2004, 306, 865.

Design of an Intein that Can Be Inhibited with a Small Molecule Ligand. J. A. C. S., 2005, 127, 4176.

—Very good chemical biology

Visfatin: A Protein Secreted by Visceral Fat That Mimics the Effects of Insulin. Science, 2005, 307, 426-430.

—MILESTONE!