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A nurturing enviornment

 

Dr. Craig Cady’s laboratory is a special place.

Here, he observes stem cells migrating toward organ-specific cancer cells—a finding that could lead to a precisely targeted form of chemotherapy with far fewer side effects than current treatments.

Cady carefully nurtures neurons. He and his students have developed strategies to keep them alive much longer than other labs report doing. He also prods and encourages stem cells to become more like neurons and hopes that one day they can regenerate a part of the brain that has deteriorated in patients with neurodegenerative diseases.

Dr. Craig Cady, Swathy Sreekumar, Lauren Hughes

Dr. Craig Cady talks with Swathy Sreekumar, left, while Lauren Hughes studies stem cells under the microscope.

At the same time, he guides and mentors a team of students who help him tremendously with the hands-on work in the lab, giving them an experience that, as undergraduates, they are unlikely to find at many other universities. Cady says he looks for students who have passion and motivation. "When I came to Bradley, I had concerns about working with undergraduate students. But, actually, the students have done very well."

Lauren Hughes, now a senior, walked into Cady’s lab as a freshman and has seldom left, although she did go on one spring break. She admits to being "completely overwhelmed that first semester. I couldn’t tell a stem cell from a neuron, and I was in awe of the older students." The most experienced member of the undergraduate researchers, she speaks with confidence and knowledge about her work. She has planned to attend medical school after graduation, but would consider staying at Bradley as a graduate student if research funding becomes available.

When she joined the lab, they were beginning to experiment with transforming stem cells into neurons. "One of Dr. Cady’s former students, Adree Venatta, who is now in her third year of medical school, had done a lot of research to find out what combinations of factors would be most likely to influence stem cells to become like neurons. She started making cocktails of different factors [a variety of chemicals secreted by cells] and putting them on stem cells in order to activate and suppress particular genes. It’s incredibly difficult to figure out," Hughes says.

When Hughes came into the lab, they had recently moved from the stage of "just destroying the stem cells to developing cells that actually have some parameters of neurons," she says. After years of research, hard work, and trial and error, Cady’s lab now transforms adult stem cells into what appear to be extremely healthy neurons. "We’ve actually showed neurologists these photos, and they have been fooled," Hughes says. "They are shocked when we tell them they are stem cells."

Outside of the lab, Hughes has also researched the work of other scientists. "Others claim to create cells that look like neurons," she says, "but here’s the thing: no one has proved that they function like neurons."

"This is what makes us different from other labs. We are actually testing the cells for functionality."
Lauren Hughes
Senior, Bradley University

The neurons produced in Cady’s laboratory express an agent that elicits synthesis of a chemical that is lacking in specific neurodegenerative diseases. Cady and his students’ ultimate goal is to develop neurons from a patient’s own stem cells that could someday be introduced into the brains of patients with neurodegenerative diseases and, through de novo synthesis, produce chemicals missing in the disease. It might be necessary to establish a way to target these developed neurons to areas of the brain specific to the neurodegenerative disease, thereby replacing function to these areas.

Alec Witty, a student who graduated in 2007, worked for two years to develop a staining method so they could identify key parts of neurons. The team was able to stain for voltage-gated channels—one feature that makes a neuron a neuron. Stem cells don’t have them, but neurons do. If stem cells are going to function like neurons, they will need to develop these channels. The staining method allows Cady and his students to compare the stem cells with the actual neurons to see if stem cells are developing the channels.

Cady also has developed a method to test the stem cells using electrophysiology. This spring they will be testing transformed stem cells to see if they are electrically active, indicating that the cells are beginning to function like neurons.

"This is what makes us different from other labs," Hughes says. "We are actually testing the cells for functionality."

"It’s something that makes me not sleep," Hughes admits. "I feel a responsibility. But it’s exciting because we’ve gotten so far."

Ben Washburn studies stem cells migrating toward cancer cells.

Ben Washburn studies stem cells migrating toward cancer cells.

Ben Washburn, a junior who is planning to be a physician, also finds the work in the lab extremely motivating. "We’re working with human diseases here, so it’s very relevant to my future," he says.

Washburn’s time in the lab has been spent on another of Cady’s groundbreaking projects—using stem cells to treat tissue-specific cancer. He creates co-cultures of stem cells and tissue-specific cancer cells and then analyzes the migration of the stem cells toward cancer cells. "We’re not really sure why, but stem cells are attracted to cancer cells," Washburn says. "We think that cancer cells are expressing something that stem cells have a receptor for."

Cady explains that the ultimate goal is for the patient to be injected with an inert drug that will travel throughout the body. Stem cells, designed to express a protein once they reach the tumor site, will be injected near the tumor. That protein will trigger the inert drug to turn into an active chemotherapeutic drug that will destroy the tumor. Instead of sending toxic drugs throughout the body, they can be created right at the site of the tumor, using stem cells as a vehicle.

Having determined that stem cells will migrate to tumor cells in the laboratory, the team is now working on the next phase of experiments, live animal testing. Washburn says he is really excited about this next phase and hopes to be involved. The actual testing will be done in Springfield in the laboratories at Southern Illinois University School of Medicine, which has the needed equipment to track the cell migration. "It’s not just cells in a dish—this will be totally different and answer a lot of questions," he says. "For example, we’re not sure if the stem cells will actually go where we want them to or if they will collect in other tissues where we wouldn’t want them—such as the heart or lungs."

Washburn says he has been surprised by the creative research going on in Cady’s lab and by the fact that he is able to participate. "I didn’t anticipate this as a prospective Bradley student," he says, "especially the level of professionalism expected and the opportunity to collaborate with other schools."

Swathy Sreekumar agrees: "I had no idea this research was going on when I came to Bradley. Now, as a campus tour guide for prospective biology majors, I tell students that there is so much opportunity to do research at Bradley. I think people need to be more aware of what is going on here."

Having recently joined Cady’s research team, Sreekumar has been doing lots of watching and listening. Cady explains that new students have to learn the procedures and sterile techniques. "We have many biohazards in the lab. We have human tissue and toxic substances. We always wear gloves, closed-toed shoes, and lab coats. And we spray lots of ethanol." But, he explains, "if these students were at a major research institution, they would be cleaning dishes or making cultures. They wouldn’t be handling stem cells."

"I tell students that there is so much opportunity to do research at Bradley."
Swathy Sreekumar
Sophomore, Bradley University

Besides collaborating with other institutions and his students, Cady also works with colleagues at Bradley. Recently he began discussing his work with Dr. Kalyani Nair, who specializes in tissue engineering and has just begun teaching in the biomedical engineering program. "She is going to look at stem cells and how they change into neurons or how they change into heart cells,” Cady says. “We look at a cellular and protein level. Dr. Nair has the expertise to look at the cells from an atomic level to help understand how and why the cells are changing."

Cady explains that his training is in neurophysiology, but "I’ve branched out a lot. I had to learn about stem cells and cancer research. Other areas I was working on led into it. Without my colleagues in cancer research and other fields, I certainly couldn’t have done the work—and that’s becoming more and more common in science. You have to work with colleagues in other areas because we have so much competition now. A scientist has to be able to publish on a variety of topics."

He explains that science is so competitive that the National Institutes of Health currently grants funding to only about 7 percent of applications. As a result, Cady says, he has to find diverse funding sources. An important source for this lab has been foundations that raise money for neurodegenerative diseases. Locally, Joan Snyder, a Parkinson’s lobbyist and patient with Parkinson’s, holds an annual fundraiser in Peoria. "She has steered a lot of money our way, and we are very grateful."

Cady says he also appreciates the fact that Snyder brings other patients with Parkinson’s into the lab so they can see the work being done. "It’s an incredibly moving experience to see their faces when they look at the neurons and stem cells under the microscope. Joan doesn’t let us lose sight of what we are working toward. I think it’s incredibly motivating for the students."

Cady admits, however, that this can also be a little unsettling for him. "It reminds us of the tremendous responsibility that we have."