Movies, microscopes, metastasis & melanoma

Contributed by Dianne Shaw, UNC Lineberger Comprehensive Cancer Center

Jim Bear’s movies won’t win Oscars, but they may save lives. He makes movies of moving cells, movements that can help or harm the body.

Bear studies cell migration.

“Cell migration is something that’s with us from birth to death. It’s a process that happens during development when we are in the womb. It happens in our immune system when we get an infection and our white blood cells have to migrate to that site of infection. It happens inside of our brains, when neurons make connections with other neurons leading to thoughts and feelings and the things that make us ‘us.’ But it goes wrong in cancer.”

Members of the Bear Lab
Front row: Sarah Creed, Sreeja Asokan, Emma Wu, Heather Aloor
Back row: Jim Bear, Stephen Jones, Brent Hehl, Matt Kuty, Dave Roadcap

Cancer cell movement is how tumors spread or metastasize. Bear’s lab and his colleagues at UNC Lineberger are now studying the migratory process of metastasis in the lab and have learned that as in human melanomas, metastasis targets the same places- the lungs and the brain.

Bear has a personal interest in melanoma. His father died of the disease when Jim was in graduate school, and his death motivates Jim: “I want to do something about this disease to make it so that other people don’t have to go through this.”

A Howard Hughes Medical Institute Early Career Scientist Award winner, Bear is probing the steps of cell motility- how cells move- with a goal of using that knowledge to derail cancer metastasis. He conducts research on a family of proteins called coronins.

“We think these proteins have been with us for nearly a billion years on planet earth. To me, something that’s that old is doing something interesting, even if we don’t understand it. That was one of the bases on which I founded my lab.”

Coronins regulate cell migration both at the leading edge of the movement and at the point of disassembling the cell as it unattaches and moves.

Watch videos

• In this video interview Dr. Bear talks about how he got interested in becoming a scientist and a builder of microscopes to capture cell movement. Watch now. 
• In this video presentation, Dr. Bear discusses cell movement and the proteins actin and coronin. Watch now. 
• This set of videos provides a tutorial on the four steps of cell movement, with cell movies narrated by Dr. Bear.
  • Step One: Protrusion
  • Step Two: Adhesion
  • Step Three: Cell Body Translocation
  • Step Four: Retraction

Learn more about Dr. Bear’s Howard Hughes Medical Institute Early Career Scientist Award: http://www.hhmi.org/research/ecs/bearj_bio.html and
http://www.hhmi.org/research/ecs/bearj.html

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What would Mendel say?

We’ve come a long way since Gregor Mendel published his “Experiments on plant hybrids” in 1866.

Okay, so he didn’t discover genes, but Mendel did use the terms  “dominant” and “recessive” to describe the appearance of a character (like the color purple), which in today’s parlance is roughly the  equivalent of gene expression. In any event, the full significance of his work wasn’t fully realized until the 1930s.

Gregor Johann Mendel

So here we are, twenty years into the genomic revolution, flush with the knowledge that mutations  play a role in more than 2,000 mendelian diseases.   And scientists are just now realizing that it’s more of the rare and less of the common variants that explain inherited risk for most common diseases.

So,  why not use whole genome sequencing to identify people with a specific inherited predisposition? Cost is becoming less of a factor. Today a person’s entire genome can be decoded with great accuracy for about $50,000. And a recent report in Science notes that costs should plummet within a few years to about $4,400.

The UNC Cancer Genetics clinic has been active for 15 years and counsels patients and their families for hereditary predisposition to cancer in an effort to assess risk, make recommendations for medical management and identify other at-risk relatives for purposes of prevention.

Dr. Jim  Evans, Bryson professor of genetics and medicine, tells me the clinic has identified approximately 100 families whose history and pedigree information strongly suggest a Mendelian predisposition to cancer, but for whom available clinical genetic testing for known genes has come up empty. 

This implies that other genes may be out there, as yet undiscovered, which, when mutated, confer a high risk of cancer. “Identifying such genes would be a great boon to patients but also promises to shed considerable light on the underpinnings of cancer and its causation,” Evans says. 

The Whole Genome Analysis of High Risk Cancer Families, is being conducted by Evans along with genetic counselor Kristy Lee, MS, CGC; Jonathan Berg, MD, PhD, assistant professor of genetics; and Patrick F. Sullivan, MD, professor of genetics.

“This is an important and wonderful example of the way in which next-generation sequencing will make tremendous contributions to our understanding of disease. Whole Genome Sequencing (WGS) has now become affordable and is being applied to a host of human diseases,” Evans says.

“The most challenging aspect of WGS, however, will be the interpretation of the avalanche of information that is generated. It represents the first medical test for which everyone is guaranteed to have an abnormal result (because we are all mutants!). Thus, there are formidable challenges to using this information for patient benefit.”

Evans says he has no doubt that in the long run the information obtained will benefit patients. But he cautions we also shouldn’t be unrealistic about deriving immediate benefits for them. “Remember that we have known the molecular underpinnings of sickle cell disease for over half a century and yet the information has still not revolutionized treatment of that condition. ”

“Applying science to the health of the individual often moves in a frustratingly slow and incremental manner. But in the end, it is the only way forward,” says Evans.

Were he with us today, I’d like to think a smiling Mendel would agree.

Les Lang