Far from the madding crowd

Wai Jing Kee is working on a new insight into skin cancer at University College, London. Ayala Ochert reports.

Like a department full of academics jostling each other to get on in their field, the cells beneath the surface of their skin are trying to break free from the crowds of cells that surround them. Only then can they reach the "escalator" that will take them on their prescribed journey to the surface of the skin. Unfortunately, these skin cells sometimes lose track of who they are and what their purpose is - they suffer a kind of "breakdown". They manage to break away from the crowds, but they move off in the wrong direction. These aimless cells are cancerous, and the cancer has spread.

At the Imperial Cancer Research Fund, one of its brightest PhD students is studying how normal cells are released from the "glue" that binds them to the hoards of other immature cells and then go on (up the escalator) to mature. She has found the component that stops this glue from being manufactured: "Before the glue gets to the cell surface, it has to go through a processing machinery. This component makes it get stuck inside the machinery," she says.

Wai Jing Kee was born in Singapore, but came to Britain seven years ago to "experience the research-oriented atmosphere" of a British university. She studied biochemistry at King's College, London. Now 25, Kee is in her third year of a PhD with University College, London, working at the Imperial Cancer Research Fund Laboratories. She was encouraged by her tutors at King's, but it was her sandwich year at the Kennedy Institute of Rheumatology in the United States that convinced her to do research.

"I loved it - it was real research. Whereas in college, when you do a practical, you know the result already, in real research you do not know what to expect. It's very exciting, but it is a cautionary excitement. You think: 'Is that believable? Have I done the proper controls? Can it stand up on its own?'" Her work in the Keratinocyte (skin cell) Lab is not just of intellectual interest - she hopes it will lead to a treatment for skin cancer, and other related cancers, including cervical cancer. She is investigating the mechanism by which immature keratinocytes become specialised skin cells as they work their way to the surface. This process is known as terminal differentiation.

"Keratinocytes are cells that form a barrier to the environment. So we have keratinocytes in the lining of the mouth, in our gut, and, of course, we have lots of keratinocytes in our skin," she says. Cells at the skin surface make keratin, a tough, resilient protein which protects them from the environment.

By studying how normal cells undergo terminal differentiation, Kee hopes to determine what goes wrong in cancer cells, which do not differentiate to become specialised skin cells. "In cancer cells there is a regression - they forget what they are, and they start going back to early in their development when they have to divide and grow," she says.

Cells beneath the surface do not produce keratin, and they are held down by sticky proteins called integrins. They can only undergo terminal differentiation and become fully fledged, keratin-producing skin cells once they have lost their integrins.

"We know that the loss of integrins is important, but what triggers the loss is still a bit of a mystery. We think that it is one particular type of integrin, beta-1, that controls terminal differentiation. I am working on a beta-1 variant, called beta-1b. I have found that there is a short part of it that is different from beta-1a, which is interesting. I think that this sequence is responsible for holding the integrins inside the cell. Before integrins get to the cell surface, they have to go through a processing machinery. Beta-1b makes them get stuck inside this processing machinery."

When the cell receives the signal to undergo terminal differentiation it stops producing integrins, integrins at the cell surface stop functioning, and those integrins being produced inside the cell are locked inside. "It's a very efficient, a very quick, way of switching things off. Integrins are stopped at all levels of production," says Kee.

In the advanced stages of skin cancer, cells can also lose their integrins and then break off. "So, when you hear of a cancer 'spreading', that's how it occurs. I think that if we knew what makes a cell lose it integrins, then we could stop the cancer from spreading," she says.

Fiona Watts, Kee's supervisor, thinks that Wai Jing is one of their most promising students. When she finishes her PhD in October next year Kee intends to continue in the same line of research, possibly in the US.

But she will be sad to leave the ICRF: "It's a really good place to work. The interaction is just really, really good, and that's very important. By talking to other scientists, some experiments get born."

At the ICRF, graduate students are trained in public speaking, particularly in communicating scientific ideas to a lay public. Wai Jing took the opportunity of using these skills when volunteers from ICRF shops came to visit recently. "I think it's very gratifying that there is this return. They are working very hard to fund what I do, so I think I should let them know exactly what that is," she says.

Her role model is her supervisor: "She is a successful woman, she runs a big lab, and so, in a sense, I do look to her and think, 'That could be me in ten years' time.' I would like to have a lab of my own at some time in the future."

Despite this positive outlook, she envisages big problems in continuing her career if she were to have children: "I don't know where I would get the time, although I would like to, eventually. I still have a lot more time - biological time! But I think it would be a huge juggle to manage the career side, the home, and a baby as well. At the moment, I am just about keeping up with maintaining a liveable house and working."