The American Cancer Society has awarded a four-year, $720,000 grant to Boston College Associate Professor of Biology Marc-Jan Gubbels for research into potential new drugs that can prevent the onset of toxoplasmosis in cancer patients with weakened immune systems.
The parasite Toxoplasma gondii has infected one out of every five people in the U.S., typically remaining dormant in healthy individuals. But when the immune system is weakened, the parasite attacks, wreaking havoc on the patient's body and often causing death.
Gubbels, who specializes in parasitology, said he's grateful for the opportunity to advance Toxoplasma gondii research as a means of improving the health of individuals at risk for toxoplasmosis.
"The American Cancer Society has given us a unique opportunity to take a new approach toward identifying potential targets to combat a deadly disease," said Gubbels. "This is a novel approach and we're excited to move forward with our work."
Among those most at risk for the stealthy killer toxoplasmosis are cancer patients whose immune systems are compromised during chemotherapy and other treatments that weaken the body's defenses. While there are drugs that can help hold the illness in check, they produce unwanted side effects in some patients and also inhibit the effectiveness of some anti-cancer drugs.
Gubbels, whose work has helped to unlock some of the genetic mysteries of Toxoplasma gondii, is researching new ways to prevent the spread of the parasite by limiting its mobility and effectively trapping it within the cells where it attacks.
The American Cancer Society grant will support work by the Gubbels' lab that could lead to the development of new drugs that can prevent the parasite from attacking its unsuspecting hosts. Patients battling cancer are particularly vulnerable when potent anti-cancer treatments weaken their immune systems.
"We're trying to find out how this parasite gets in or out of a cell," said Gubbels. "Cells in our bodies don't invade other cells, but Toxoplasma gondii cells have dedicated machinery to do that. We have a basic understanding of this, but we don't know how it all fits together or is controlled. If we can understand that process, we can design drugs that can counteract that and hopefully save lives."
Toxoplasma gondii is carried by almost every warm-blooded animal and is spread through ingesting cysts present in undercooked meat or in cat feces. An intra-cellular parasite that lives within the cells of its host, the parasite must first enter a cell and then, after consuming its contents, exit the cell. Gubbels and researchers in his lab are looking for ways to control entry and exit by turning off genes that inform the parasite's mobility.
Invasion and egress share many features, Gubbels added. But they are poorly understood at the molecular level. In addition, current anti-toxoplasmosis drugs do not target either invasion or egress.
The Gubbels research team will take normal strains of the parasite and then create gene mutations within them. After singling out the altered parasites, researchers will determine whether the genes involved play a role in the parasite's entrance to or exit from a host cell. Gubbels said the goal is to find proteins with essential functions in a defining pathogenic process not targeted by current drugs.
"The overarching goal of our work is to increase the number of treatment options for toxoplasmosis, in particular to develop drugs with fewer side effects," Gubbels said. "The best drug targets are found in biological processes that the parasite does not share with the host. The process we are interested in is the process of how the parasite gains access to the cells of the host, and subsequently, how it is able to escape from the host cell upon completion of replication."
Advances in cellular biology and genome sequencing have paved the way for this type of project, Gubbels said. Armed with these tools, researchers can make more focused inquiries into the functions those genes control.
Toxoplasma gondii has steadily grown as a research priority since the 1960s, when it was discovered that cats host the parasite in its reproductive stage. Pregnant women are urged to avoid close contact with cats and cat feces during pregnancy, since toxoplasmosis can cause birth defects. During the onset of the AIDS crisis in the 1980s, toxoplasmosis claimed many victims whose immune systems were compromised by the virus, Gubbels said. The decoding of the parasite's genome within the past decade has further advanced research into a largely unseen killer.