Team of Two: A Dynamic Duo in the Research Lab

By Susan Andrews
April 8, 2015

Eliana Toren, a junior biology major, became fascinated with endocrinology in seventh grade. A native of El Paso, Texas, Eliana said, “I was and still am amazed at how hormones control every single aspect of your body from your emotions, to how fast your heart beats, to your metabolism. Every system controls every other system in your body in one way or another.”

When Toren met Dr. Craig Cady, associate professor of biology, she told him of her profound interest in endocrinology. “He said he had never met a freshman who expressed this interest so keenly,” she recalled. “Then I looked up at the shelves in his office, and I saw a sea of books with endocrinology titles.” 

Spending much of her first two years at Bradley learning how to conduct basic research, Toren was ready to assist Bradley graduate student Feras Altwal on his graduate project in search of a solution for parathyroid disease. “About 10 percent of people with thyroid problems have parathyroid disease,” he said, added that parathyroid cells are needed to produce hormones that generate and regulate calcium. Without fully functioning parathyroid cells, patients must take massive doses of calcium and can easily take too much or too little if not complying with a daily regimen. 

Dr. Mark Holterman, professor of surgery and pediatrics at University of Illinois College of Medicine at Peoria and a close collaborator of Cady’s, encouraged Altwal to seek a cure: “Dr. Holterman explained that many of his patients suffered from parathyroid disease with symptoms of muscle pain and spasms, weakened bones and more — with children, this can prove lethal.”

Two years later, Altwal and Toren, under Cady’s mentorship, achieved a scientific breakthrough that no one else in the world has done before.

The Process

In Phase One, Altwal and Toren created parathyroid cells using adult stem cells by culturing and growing normal parathyroid cells taken from human and pig tissue, which required experimenting with different conditions and growth factors.  The pair employed three different methods in the lab; of those, only one method was successful in growing normal parathyroid cells which few labs in the world have. With an awareness of the appearance of normal parathyroid cells and associated characteristics, they now have a “positive control” with which to compare the adipose (fat) stem cells they were hoping to change into functioning parathyroid cells.  

Cady noted this had been done with embryonic stem cells but not with adult stem cells. One of the benefits of using adult stem cells to treat a disease is that one’s own cells are less likely to be rejected when re-implanted into the body, according to Cady.

In Phase Two, Altwal and Toren grew cultured adipose (fat) stem cells under special conditions (without antibiotics), applying special factors for 26 days to induce the stem cells to become parathyroid cells. 

“Culturing and changing stem cells into parathyroid cells is a 26-day day process, and we were unable to use antibiotics when culturing the stem cells, which is a different and increasingly complex protocol than most,” Toren explained.  When culturing the stem cells, they must be tended to every day, requiring from one to five hours per day. “This was quite a time commitment, especially as we had several failed experiments before we succeeded,” she remarked.

Toren said that for the first 13 days of culturing the stem cells, they needed to stress the stem cells before differentiation. At day 14, a growth medium composed of two factors that would differentiate these stem calls into parathyroid cells was added, and they began to proliferate and form colonies.

The Discovery

Altwal remembers well the day back in June 2014, when the eureka moment occurred. “I was looking under the microscope in the laboratory and saw the cells glowing green,” he recalled with unabated excitement. “This demonstrated that we had succeeded in creating the parathyroid cells.” Altwal was able to determine the successful expression of parathyroid proteins through the ELISA method, a test that uses antibodies and color change to identify a substance.

He reached Cady and Toren by telephone to share the astounding news: “Everyone was happy and could not have been more pleased with the outcome.”

Toren was honored to present the findings of their research at the World Stem Cell Summit in San Antonio, Texas. “I believe I was the only undergraduate student presenter at the event,” she said.

Altwal, who graduated with a master’s in biology from Bradley last summer, has been working on an immunological solution to diabetes with Holterman. He was recently admitted to Rosalind Franklin University of Medicine and Science to pursue a Ph.D. in biology.

Next Steps

Toren is continuing the research with the goal of determining how fast the cells are secreting the parathyroid hormone using the ELISA method.

In collaboration with a group of Bradley’s mechanical engineering students guided by Dr. Kalyani Nair, a nanomaterial microfiber mat is being developed that could be used to return parathyroid cells to patients.

Cady extolled the time and effort of both students by emphasizing the strengths of their complementary skill sets — Altwal for his clinical research and Toren for her basic research: “The diverse methods that they have learned in scientific research will support them in advanced research.”

The research study has been submitted to the Journal of Pediatric Surgery for publication. 

The joint research grant was awarded to Bradley University and the University of Illinois School of Medicine by OSF Saint Francis Medical Center/UNICOMP.