Edward J. Pearce
2001 - Dr. Edward Pearce - Learning to Thwart Parasitic Worms
February 2001 -No one likes to think about parasitic worms living inside them, draining away nutrients and wreaking havoc with tissues andorgans, but in many parts of the tropical world, living with parasitic worms, also called helminthes, is a fact of life. Infections by helminthes rank second only to malaria in terms of negative health effects of parasitism. One in four people world wide, many of them children, are estimated to be infected.
Worms are particularly clever parasites in that they have developed ingenious ways of hiding from the human immune system, allowing them to escape an all out assault that could eliminate them from the body. But how do they do it?
Edward Pearce, Ph.D., a BWF scholar in molecular parasitology and associate professor of parasitology at Cornell University College of Veterinary Medicine, is studying how a particular parasitic worm called Schistosoma mansoni is able to set up residence in the veins leading from the intestine to the liver, living there for five to 10 years and sometimes longer. Long-term exposure to the parasite can cause serious liver, intestinal, and bladder damage. In children, infection stunts growth, and some studies have shown damage to learning ability.
Ever since he was a college student, Dr. Pearce has been fascinated with the effectiveness of the worms’ strategy and their ability to evade the human immune system.
“Just think,” he says, “what it would mean to transplantation if we could understand how whole, living animals like these worms manage to live inside us for so long.” Currently, the field of organ transplantation is severely limited by immune system’s reaction and even eventual rejection of “foreign” organs implanted into people to replace failing ones. Only daily regimens immune-suppressing drugs stop transplant patients from rejecting their new organs. Parasitic worms have a lot to teach us about evading the immune system.
And by understanding how worms thwart the immune system, says Dr. Pearce, we can begin to think about developing a vaccine to stop infection.
Scientists know that in an elaborate life cycle, worm eggs hatch in the water and seek out a specific fresh watersnail, which serves as a type of incubator for the developing worm.When it’s ready, the worm leaves the snail and enters the water, where it attaches to unsuspecting bathers, burrowing into the skin and entering the blood stream. Somehow, the tiny worms are able to travel through out the body riding along in the bloodstream for two-to-three weeks, until they reach their destination: the veins leading from the intestine to the liver. Here they set up residence and begin mating and producing new eggs, which are swept through the intestines and deposited with feces to begin the cycle anew.
Dr. Pearce began about six years ago to study how the worms know when they have reached theirdestination. He reasoned that they must have some kind of signaling system that lets them know when they are in the right veins. He began looking for signaling receptors on the surface of the worm’s body.
What he found was that the worms have a chemical receptor on their bodies that is in the same family as a human receptor called transforming growth factor beta (TGFb) receptor 1. These receptors are used by cells throughout the body to regulate growth, proliferation of new cells, and development into specialized cell types. There are dozens of members in the TGFb family that bind to this type of receptor. Dr. Pearce is using his BWF Scholar Award to fully investigate his discovery. He isolated the receptor and cloned it so he could study it further. But he realized he needed to find out what human protein was the target for this receptor.
“We really needed to identify the human ligand to understand the consequences of this discovery,” he said. Recently he and his colleagues identified at least one target as bona fide TGFb and showed the worm receptor can bind it and initiate a signaling process. “That may sound obvious,” he said. “But there are many, many related proteins that it could have been. The challenge now is to establish the consequences to the parasite.”
Dr. Pearce is beginning experiments using mice that don’t make TGFb. He wants to find out if the worms will be able to localize and function properly without TGFb present. If not, he may have discovered a key element to the worms’ localization strategy by using proteins within the human body to help guide themselves.
He acknowledges that working on these parasites is not easy and requires a lot of patience. For one thing, the parasites won’t grow in culture – they are dependent on their hosts for survival. And they take a long time to mature.
“There are a lot of important molecular tools – like knock-out mutants and gene expression mutants – that have not been developed for worms,” he said. “Development of tools for work on these parasites is key to moving this field along.”
Questions for Dr. Edward Pearce:
Name: Edward J. Pearce, Ph.D.
Recipient: 2000 Scholar in Molecular Parasitology; 1994
New Investigator in Molecular Parasitology
Academic Title: Associate Professor, Department of
Microbiology and Immunology
Affiliation: Cornell University College of Veterinary
How did you first discover you wanted to be a scientist?
I never remember not wanting to be a biologist of some sort or another.
Why did you choose to enter your particular field of study?
My parasitology professor at the University of Wales Aberystwyth, John Barrett, made the whole story of how parasites are able to avoid the immune response and survive in their hosts so intriguing that I became hooked. It was a choice of trying to work on African trypanosomes or schistosomes and I had an opportunity to do the latter.
What has your BWF grant meant for your research?
The chance to invest more resources into the issue of how schistosomes receive environmental cues; it has not been easy to obtain funds for this area of research.
What is the best thing about your job?
The intellectual challenge, the opportunity to work with some very smart people, and the freedom to more or less set my own timetable.
What is your philosophy with respect to your research?
Don’t do “me too” research.
What kind of advice would you give a scientist just entering academic research?
Focus on the question, do your experiments as carefully as you can with a view to making as few errors as possible, and publish. Collaborations can be great, but remember to keep adding to the list of publications on which you are first or last author. If you don’t get your grant first time, keep trying. When you get your own laboratory, make sure you spend as much time as possible in there rather than in your office.
What area of science is in most need of new researchers?
There is a very real need for more scientists to study helminths. There are very few young scientists choosing to stay in this field.
If you had unlimited resources, what one big scientific question would you pursue?
Probably the same ones that I am pursuing now.
What do you do for fun?
Watch films, watch wildlife, read and travel.
What do you plan to do when you retire?
As little as possible.
What is your favorite book?
One of them is: “The Spy Who Came in From the Cold,” by John LeCarre.
Who gets worms?
Anyone can become infected with schistosomes when they swim or bathe in fresh water lakes and streams that contain the tiny parasitic worm. They are found in wide areas of 74 tropical countries in Africa, South America, and Asia. More than 200 million people are infected, many of whom are children. Anyone traveling to these areas is at risk of infection if they come in contact with infected water.
What are the symptoms of infection?
For travelers, the symptoms are nausea, fever, malaise, abdominal pain, and sometimes bloody stools. These symptoms of early infection are not common in people who live in endemic areas, who have gained some tolerance to initial infection by living in close contact with the parasites over many generations. Chronic infection can lead to life threatening complications associated with liver fibrosis. Definitive diagnosis requires finding eggs in the feces.
Can people be cured?
Effective drug treatments for schistosome infection exist. A drug called praziquantel can rid the body of the worms after a one- or two-day treatment. However, it is currently the only generally accepted treatment and resistance to the drug has been detected in some worms. New medicines and a vaccine are in various stages of research. In endemic areas, only major public health campaigns in places such as China have reduced long-term infection. In most areas, treatment is limited.