Three New Publications!

It’s been a busy spring here in the Stupack Lab.  We’ve been coalescing several manuscripts for publication, and we are proud to announce that we now have a few additions to our publication list:

Graf R, Keller N, Barbero S, Stupack DG. Caspase-8 as a Regulator of Tumor Cell Motility. Current Molecular Medicine. (In Press)

Graf R, Barbero S, Keller N, Chen L, Uryu S, Schlaepfer D, et al. Src-inducible association of CrkL with procaspase-8 promotes cell migration. Cell Adhesion & Migration. 2013 Jun 10;7(4). PubMed PMID: 23751956. Epub 2013/06/12.

Shanique A. Young, Ryon Graf and Dwayne G. Stupack (2013). Neuroblastoma Integrins, Neuroblastoma, Prof. Hiroyuki Shimada (Ed.), ISBN: 978-953-51-1128-3, InTech, DOI: 10.5772/55991. Available from: http://www.intechopen.com/books/neuroblastoma/neuroblastoma-integrins

“Caspase-8 as a Regulator of Tumor Cell Motility” has been accepted to Current Molecular Medicine and is a review article on the molecular mechanisms of how caspase-8 can promote cellular migration, a process central to tumor metastasis, independent of its better-defined role as a cell death protein.

“Src Inducible Association of CrkL with Procaspase-8 Promotes Cell Migration” has been accepted to Cell Adhesion and Migration and is available here. In this study, we expand upon a mechanism by which Caspase-8 (“Procaspase-8″ indicates the immature non-activated version of the protein) can promote cellular migration, identifying a new interacting protein (CrkL) and the modifying enzyme (Src) that facilitates this interaction.

The book chapter: “Neuroblastoma Integrins” is currently available via open access: http://www.intechopen.com/books/neuroblastoma/neuroblastoma-integrins We reviewed and consolidated information about the role of integrins (cell adhesion molecules critical to development, cell migration, and other roles) in neuroblastoma, the most common pediatric solid cancer. We also expand upon current concepts of therapy, and suggest new avenues for investigation by clinical pediatric oncologists.

Our graduate students at the ASMB – SFG conference

16 November 2012

This last week our two graduate students Shanique Young and Ryon Graf presented posters of their research at a major international scientific conference held right in their own backyard: downtown San Diego. To the backdrop of the beautiful white-sailboat-filled San Diego Bay, the Sheraton Hotel hosted scientists from as far away as Israel and Finland as they converged upon the joint symposium of the American Society of Matrix Biology and the Society for Glycobiology.

Image: Ryon poses with his research poster.

Shanique presented her new research on the roles of integrins in models of neuroblastoma metastasis, and Ryon presented on conditional protein interactions that might link together therapeutically relevant areas of cancer biology.

Both students received great feedback on their work, and enjoyed the open, collaborative environment. Although science is communicated more and more electronically in the 21st century, there are many positive benefits to the more socially inclined research conferences such as these, like forging future collaborations.

Busy Summer

Summer might be winding down, but things are busy here in the Stupack Lab. Our scientists are currently performing experiments with: purified protein, cancer cells, cancer stem cells, cancer cells in extracellular matrix and mock-cancer environments, with mice, and slowly coalescing data, ideas, insights, and models into several manuscripts that are being prepared as this is typed.

Happy Summer!

Quote of the day

The absolute worst ideas are the ones people keep to themselves.

Happy Pi day!

Today is 3.14 (year 2012). Happy Pi day to all the math and science fans out there.

How to properly water a pet cactus

Everything in a medical research laboratory must be properly cared for and maintained. Here is Ryon demonstrating proper cactus watering technique, complete with carefully measured water volume, protective clothing and eyewear. It’s much better than pouring water on the poor cactus’s head or trying to lift him out of his pot.

Retrovirus?

A little science humor:

Most information in biology follows the path: DNA -> RNA -> Protein. But, certain viruses can also do RNA -> DNA. So, they were named “retro” viruses. Their information literally “goes back” into the host genome to complete its life cycle.

image source: http://kqedscience.tumblr.com/post/13829672539

Ryon passes Qualifying Exam

We are pleased to announce that Ryon Graf has passed his Qualifying Examination for his PhD. In about two years’ time he will attempt to defend his thesis work, the course of which is thesis committee has now approved. One earns a PhD in biology (or Ryon’s case, Molecular Medicine) once one has demonstrated to have made a contribution to science, and is fully capable as an independent scientist.

However, one does not need a PhD to be a scientist. At its core, a scientist is one that defines their world by repeated experimentation and observation, and contributes this knowledge to a wider audience. A PhD is one path to get there.

Cloning genes?

For many, the term “cloning” conjures up images of creating replicas of animals or people played out in arenas of science fiction and comedy. We do cloning in the lab, but it does not quite look like Hollywood’s depiction. We do make copies… of genes, not entire organisms.

So, what does the process look like? Wikipedia has a fairly good article on molecular subcloning, so it would be a waste of time to re-invent the wheel. Rather, we offer a photo from a recent cloning experiment.

The dots are colonies of bacteria that each contain a different human gene. The bacterial colonies are growing (upside down) on a bed of agar, a gel-like substance that contains nutrients for the bacteria to grow.

The cloned genes will be replicated by the bacteria, then we can trick the bacteria into making proteins that we use in our research on cancer genes and proteins. Similar processes are used to create insulin for diabetes patients and the raw materials for vaccines.

The bacteria that we use in lab is practically harmless and would not likely grow outside of the manicured environment of our lab.

Years ago this was the absolute cutting edge, and now the techniques and molecular biology are so well understood that we even teach this process to bright high school students.

The Stupack Lab, Summer 2011

Welcome to the Stupack Lab. 

This is a series of posts on cell biology and cancer research.  It is aimed at the everyday reader, and not at a scientific audience.

Our lab studies the mechanisms by which cells sense information in the extracellular environment.  In particular, we are intereted in how this information is translated into choices in cellular ‘attachment’ to the extracellular scafold of proteins known as the extracellular matrix.  In turn, binding to the matrix, and its relative composition, governs in large part whether cells choose to migrate,  live, or die. 

While this last choice (die) seems strange, most cells in the body are programmed to undergo a form of cellular suicide, called apoptosis.  This usually occurs when they find themselves outside their normal environment.  The suicide programming is very context-sensitive, however.  Depending on what else is happening in a given cell’s local microenvironment, it is sometimes offered an opportunity to survive and move. 

That’s where the extracellular matrix comes in.  Just as in the movie (the matrix), the scaffolding that cells stick to holds an enormous amount of information, and manipulating the matrix can manipulate how cells react.  This information is encoded in several ways.  For example, a matrix may have binding sites for some cell-attachment receptors, but not others (and a cell definitely knows which receptors it is using). The matrix may be very rigid, or quite flexible, which changes the nature and duration of signals that are transmitted into the cell. The matrix may also act as a depot, holding a variety of soluble growth factors that are stored until they are needed.  The matrix is slightly different from tissue to tissue, and as you might expect, it changes during development and aging, and during wounding.  In fact, a blood clot is an excellent example of rapid formation of a new matrix, composed largely of proteins called fibrin and fibronectin, and many tinier-than-average cells, called platelets.  The information encoded in this matrix is going to be much different than in, say, the collagen one might have inected for cosmetic reasons.    

This makes a lot of sense if you consider the things that occur in your body on a daily basis that could use matrix guidance.  Little injuries that require cells to migrate in and repair, or  white blood cells traveling between your blood and tissues, surveying for threats, are good examples of this.  The choice between cell survival and death, and the ability to move, are important factors for immunity, healing and development. 

However, tumor cells commonly find ways to misinterpret or ignore information in the local protein matrix.  Often, tumor cells will “overwrite” the existing matrix with one of their own.  The result of any of these events are tumor cells which are more aggressive because they survive better and can elect to migrate to other tissues.  These are often the most dangerous cells in a tumor, accounting for spread and resistance to chemotherapy.

My  lab has assembled a dedicated  international team to understand some of the mechanisms that control how tumor cells can accomplish this, and to begin to devise new strategies to understand, detect, and block survival and migration.