The Scientific Activist

Blogging on Peer-Reviewed ResearchI think I can finally call myself a legitimate scientist (whatever that means), since last week one of the papers I worked on during my undergrad at Texas A&M University was published in The Journal of Cell Biology (JCB). I’m the fourth author on the paper, meaning that I was only peripherally involved (and made a much smaller contribution than the first author, Dr. Brian Saunders, and my advisor, Dr. George Davis, among others). Regardless, this is my first appearance in the peer-reviewed scientific literature, and since I (not surprisingly) find the subject of this paper incredibly interesting, I’ll take this opportunity to give my readers a quick introduction to blood vessel development and to put the findings of this study in perspective.

A blood vessel consists of multiple layers of cells forming concentric circles about a central tube through which blood flows. Although the details of the architecture can vary, in its smallest and simplest form (a capillary), a blood vessel consists of an inner layer of endothelial cells surrounded by supporting pericytes. The process of forming a new blood vessel from an existing one is known as angiogenesis, and when it occurs (in growth and development, in wound healing, or in tumor formation, for example), angiogenesis appears to unfold in a few discreet steps. Use the following diagram to help visualize the process as I describe it below:

i-1542706e11b062cad936fa87226249ac-angiogenesis-model.gif

In response to a pro-angiogenesis stimulus (B), endothelial cells from the inner layer of the preexisting vessel begin to break away and migrate toward the source of the stimulus. This migration involves a complex interplay of different activities, as the individual cell has to reach out and grab onto the protein web in front of it, while at the same time letting go of the web behind it. Interestingly these endothelial cells also release proteases that chop up this protein matrix in the process to make a path for the cells to travel down. While all of this is going on, other molecular signals tell the supporting cells, pericytes, to stay where they are and not interfere with the process.

The endothelial cells then connect with each other to build a new tube (C). This new endothelial cell tube, however, is incredibly unstable and prone to falling apart without the help of its supporting cells. At this point, the new endothelial cell tube releases molecules that attract pericytes, which then stabilize the newly formed vessel, completing its development (D). The means by which pericytes stabilize these tubes has remained unknown, and various ideas have been hypothesized. In the new paper, we show that the naked endothelial cells are unstable, at least in part, because they continue to chew up their supporting protein matrix–a process that is necessary for their migration and development into tubes but can eventually lead to their destruction.

When pericytes come into contact with endothelial cells, both release unique protease inhibitors (TIMPs) that serve to prevent this degradation, thus stabilizing the new vessel. These findings are interesting, because they offer a simple but elegant model of protease regulation to explain blood vessel stabilization. When endothelial cells are first migrating away from the preexisting vessel, they need to use proteases to make carve out a path through the protein matrix. The presence of protease inhibitor-producing pericytes, then, would strongly interfere with this process. When stability is needed, though, after the new tube has been formed, then pericytes are recruited to provide stability by inhibiting this intrinsic protease activity of endothelial cells.


W. Brian Saunders, Brenda L. Bohnsack, Jennifer B. Faske, Nicholas J. Anthis, Kayla J. Bayless, Karen K. Hirschi, and George E. Davis, Coregulation of vascular tube stabilization by endothelial cell TIMP-2 and pericyte TIMP-3, Journal of Cell Biology 175 (2006), 179-91.

Comments

  1. #1 Paul Browne
    October 17, 2006

    Well done, it looks like good work. Getting a publication out of your undergraduate placement is as good a start as any to your career.

  2. #2 luca
    October 18, 2006

    Congrats, Nick!!! Your summary looks clear enough. I’ll snap up the paper and have a look – uhm, or may be not, seeing the pile of work in my desktop…

  3. #3 sonia
    October 19, 2006

    congratulations!!!

  4. #4 Rob Dejournett
    October 20, 2006

    Congrads! I just published my first first-author. It’s definately an experience (as in, why the heck did this take so long (5 years), and how can I speed up the process?). Starting with a paper in JCB is a great start. If I could give any advice, I’d say don’t worry about 1st authors in high-impact journals, if you are interested in building up your CV and not just publishing one paper every 5 years. Go for mid-tier journals if its your first first-author. Go for as many middle-authors as you can get. Go to as many conferences as you can. It all counts on the CV. Things that dont’ really count: being put in the acknowledgements section, presenting at small, not-international conferences, all the b.s. you go through in science that isn’t publishable…

  5. #5 Dave Kerstetter
    October 21, 2006

    That’s great news, and congrats are certainly in order. I tend to agree with Rob above — save the big papers for later until your CV is a little well-developed — but what do I know? I’m still a post-doc myself. Good luck!

  6. #6 Organic Chemistry
    February 22, 2007

    Congratulations, here is to the first of many.

  7. #7 Pete Mohr
    January 15, 2008

    Congrats Nick. Great work. For the record, have you looked into the work done by Dr Louis Ignarro (Nobel Prize Winner) on Nitric Oxide? Another item to look at is the new study being done on Glyconutrients as pertaining to cellular communication. Keep up the good work Thanks.

  8. #8 vierra angelina
    December 11, 2009

    congrats nicky! :)

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