Biomedical Breakthroughs

Indiana researchers are making progress on everything from tracking cancer to healing diabetic wounds.

by Laurie Wink

Innovative research at area universities is producing promising results for advancing health and medical care. Breakthroughs could lead to new ways of tracking cancer cells, treating colitis and healing diabetic wounds, to name a few possibilities. But the process of taking discoveries from bench to bedside requires years of lab work, clinical trials and considerable funding.

Patrick Bankston, director of the School of Medicine and dean of College of Health & Human Services at Indiana University Northwest, says, “The medical school fosters basic disciplinary research, but then there's the next step. You hear stories of impending breakthroughs, but they will take years to reach the market. A lot of people don't understand that.”

Dipika Gupta, IU School of Medicine associate professor of biochemistry and molecular biology, agrees that a long lead time is required to yield results that make a difference in people's health. About 15 years ago, Gupta and her husband Roman Dziarski, IU professor of microbiology and immunology, discovered a family of proteins that help prevent bacterial infections. The discovery could lead to treatments for inflammatory diseases, such as colitis, asthma and psoriasis.

“These proteins regulate the bacterial population,” she says. “If they're not working, the bacteria cause inflammation. We've come a long way in our understanding but no way are we close to a complete understanding. Inflammatory diseases are complex and do not have a single cause.”

Gupta is now studying the role of proteins in excessive weight gain in laboratory mice. She says it's important to understand contributors to obesity because excess weight is a factor in diabetes and heart disease.

Gupta and Dziarski serve on the scientific advisory board of IVDiagnostics Inc., a research and development company in Crown Point. IVDiagnostics translates basic research discoveries into technology for mainstream medicine. Frank Szczepanski, cofounder, CEO and president of IVDiagnostics Inc., says the company has invested five years in developing a diagnostic test for circulating tumor cells (CTCs)–the major cause of death in cancer patients. The new technology uses an optical scanner attached to a laser probe on a patient's vein to get real time information, without taking a biopsy or blood sample.

“It's 150 times more effective than the typical 10 milliliter blood sample in finding circulating tumor cells at early cancer stages,” he says. “This device will tell a physician if the patient needs further treatment.”

Szczepanski's passion for the project is personal. His wife was diagnosed with breast cancer in 1989 and received conventional treatment: surgery, chemotherapy, radiation and years of medication. She was in remission until 2007, when it became clear the cancer had spread. She died in October 2012, after undergoing what Szczepanski calls “years of torture.”

IVDiagnostics is testing the CTC technology in clinical trials at three Indiana medical facilities. Szczepanski says it could be approved for widespread use within a few years. The return on investment could be significant, but a lot of money has been invested up front.

“Every little step has to be validated and revalidated and tested against humans,” Szczepanski says, adding that a single pilot trial costs $1 million, or about $10,000 per patient.

More immediate applications are emerging from Purdue University Calumet's Center for Innovation through Visualization & Simulation. Chenn Zhou, director of the CIVS, says the center is combining advanced simulation techniques with virtual reality technologies to solve real-world problems for organizations across Northwest Indiana and beyond.

The center's three-fold mission is innovation, application and education. Over the last six years, the CIVS has collaborated with more than 90 organizations–including hospitals, companies, schools and government agencies–on 140 different projects. Hundreds of university students have gained experience in simulation and visualization research that has opened up exciting career opportunities, Zhou notes.

“Both simulation and visualization together can really help biomedical research in terms of looking at causes of disease, surgical planning and diagnosis,” she says. “It also has educational applications that are tremendous and can enhance learning and training, which is critical for health care.”

Several biomedical projects are underway. A Munster physician initiated a spine modeling project to find the best treatment options for patients. Standard medical imaging technology, such as X-rays and MRI, gives a two dimensional picture of patient conditions. By using a 3-D model, a physician can simulate the effects of stress and other scenarios to get a more comprehensive view.

A CIVS project by Bin Chen, professor of electrical and computer engineering, is creating a 3-D virtual model of the human brain that shows how signals pass through certain areas of the brain to control specific body functions. Zhou says the brain imaging research could lead to greater understanding of Alzheimer's disease and sports-related concussions.

At the University of Notre Dame, a research team led by Jeff Schorey is working on a diagnostic test for tuberculosis that is fast, accurate, inexpensive and easy to use in less developed countries, where most cases occur. Schorey, a professor of biological sciences and associate director of Notre Dame's Eck Institute for Global Health, says the immediate goal is to identify biomarkers, in the form of mycrobacterial proteins, that signal active cases of TB.

“We're hopeful that we're going to be successful but we're not at the stage of product development. If things go like we hope, if could be five or six years before field testing occurs.”

Schorey's Notre Dame team is collaborating with scientists at Colorado State University and University of California at San Francisco on the project, funded by a $1.5 million grant from the Bill and Melinda Gates Foundation.

Schorey says TB kills about 1.5 million people worldwide each year. The disease is most prevalent in low- and middle-income countries, where cases often go undetected because of 100-year-old testing methods and a lack of basic infrastructure, such as reliable sources of electricity.

“In the United States, people would go to the doctor and get treatment,” he says. “In many parts of the world, going to a clinic or physician is logistically hard to do.”

Although cases of TB are rare in this country, outbreaks do occur. In Sellersburg, Ind., 85 people tested positive for the TB bacteria in June, after being exposed to a student at Rock Creek Community Academy who had a confirmed case of TB. The exposed individuals were treated with antibiotics to prevent the disease from spreading. Schorey cites the incident as an example of how easily infectious disease can be transmitted.

“Infectious diseases don't know boundaries,” he says. “TB is a very easily transmitted disease. With this age of globalization and the ease of going from one country to another, it can come to the United States at the drop of a hat.”

Mayland Chang, Notre Dame research professor of chemistry and biochemistry, has a $1.6 million grant from the American Diabetes Association for a five-year study of wound healing in diabetics. More than 29 million Americans–about 9 percent of the population–suffer from diabetes. The disease causes nerve damage and weakened immune systems that interfere with proper wound healing and result in amputations. In fact, some 70,000 diabetes-related limb amputations are performed in the United States every year.

Chang wants to understand why diabetic wound healing is different from the normal healing process. Using laboratory mice, her team has identified two types of proteins, called metalloproteinases (MMPs), that are involved. MMP-9 appears to cause diabetic wounds and MMP-8 accelerates wound healing. She's working with medical staff at the Elkhart General Hospital Center for Wound Healing to find out if the same process that works in mice also works in humans.

Right now, there are no effective treatments for healing diabetic wounds. While her research looks promising, Chang says it will take at least five more years of work and about $2.5 million to produce an actual treatment.

“It requires not just research but others coming together to make this happen,” Chang says. “Before we can move to clinical trials, we need to do toxicological studies in a large number of animals. That can't be done in a university lab. We need to contract with a chemical manufacturer and a toxicology laboratory. Someone has to be interested in raising funds to bring it to the next phase.”

Chang says pharmaceutical companies don't want to fund work until it can result in a marketable product, which makes it challenging to get funding for earlier research stages, she says. “Many discoveries from the lab die because no one picks them up,” Chang says.

To make sure that not all good ideas get lost, the Indiana Clinical and Translational Sciences Institute (CTSI) was created in 2008 with a multimillion dollar grant from the National Institutes of Health. The statewide entity provides pilot funding, consultation and technical assistance for translational research that could improve human health, according to Anantha Shekhar, CTSI director.

“New biomedical discoveries at the basic science level are occurring at an extremely rapid pace,” he says, “but the progression of these new ideas to the market as therapeutic products and the implementation of new findings into routine disease management face enormous delays.”

The CTSI is an innovative public and private partnership of corporate, community and government entities being led by the major health science schools at Indiana University, Purdue University and the University of Notre Dame.

Shekhar says, “The main reason the three schools are working together is that they have complementary strengths. The problems of health in Indiana are too big to be solved by any one institution and we can be much more effective and competitive for funding together as opposed to competing separately.”

Through groundbreaking scientific discoveries made by university scientists, grants from major funders and collaborations with private companies, Indiana is making significant contributions to improving the health of Hoosiers and people throughout the world.