The journey to a medical breakthrough often begins with a single entity: a single theory, a single cell, a single research dollar.
In the field of research, however, those first dollars of funding can often be difficult to obtain. According to Dr. Keith Crist, associate director of the Jacobson Center for Clinical and Translational Research, this lack of substantial support for pilot research projects was the impetus for UT’s Translational Research Stimulation Awards.
“At the pilot stage of a research project, you’re asking very basic questions,” Crist said. “Does this investigation have merit? Can we take this one step further? Unfortunately, funding for these early stages is minimal and to qualify for the larger grants from organizations such as the NIH (National Institutes of Health) and NSF (National Science Foundation), you need to have data and preliminary results.”
UT’s Translational Research Stimulation Awards offer a starting point for collaborative research projects in pilot stages. Four researchers received grants of $25,000 each to fund projects that aim to improve outcomes for patients afflicted with chronic sinusitis, multiple sclerosis, kidney disease and cancer. The recipients and projects:Dr. Reginald Baugh, professor in the College of Medicine and Life Sciences, and chief of the Division of Otolaryngology at UT Medical Center — “Preclinical Evaluation of Photodynamic Therapy for the Treatment of Chronic Sinusitis”
Baugh and his team will develop a model for treating chronic sinusitis — a condition that, according to the Centers for Disease Control and Prevention, causes more than 12.5 million visits to medical centers each year in the United States — with photodynamic therapy (PDT).
“PDT uses light to kill the bacteria, so this is almost Buck Rogers science,” Baugh said. “Dyes you apply topically will attach themselves to bacteria. When a light is shined on them with the appropriate wavelength, it fluoresces, generating a highly unstable molecule that is toxic to whatever is in the area. Given that it’s attached to the bacteria, it kills the bacteria. We absorb the dyes onto nanoparticles, particles smaller than one-tenth of a micrometer, to permit treatments every few days instead of every few hours.”
Baugh hopes this new method of treatment will enhance patients’ options. A significant population, he noted, continue to experience chronic sinusitis despite treatment with appropriate antibiotics and surgery.
“If we can get this to work, it will be a topical treatment, not a systemic treatment,” Baugh said. “That translates to fewer allergies and interactions with other medications and the potential for no drug resistance. Our preliminary results suggest this technology has the potential to be as effective as the strongest antibiotics currently available and may reduce the frequency of surgeries.”
Baugh’s partners on the project are Dr. Sai Boddu, Dr. Fredrick Bunge, Dr. Brent Cameron and Dr. Ronald Fournier.
Dr. Miles Hacker, professor of pharmacology in the College of Pharmacy and Pharmaceutical Sciences — “Preclinical Investigations on BBR3378: A Novel Aza-Anthrapyrazole to Treat Multiple Sclerosis”
Hacker and his team have developed a medication they hope will not only cause symptomatic relief for people with multiple sclerosis, but also treat the cause of the disease itself.
“MS attacks the nervous system and the nerves that have an insulating cover around them called the myelin sheath,” Hacker explained. “It’s an inflammatory disease and an autoimmune disease; the patient’s immune system attacks the myelin sheath and destroys it, causing inflammation and scarring.”
Hacker and his team have produced an experimental drug named BBR3378 that, in pre-clinical studies, has been shown to be effective in curbing the damage of MS without the toxicity of current drug therapies. Often, Hacker said, the standard drug to treat MS — mitoxantrone — must be discontinued after a few years due to potentially life-threatening side effects.
“We think our drug decreases the reactivity of the autoimmune cells so they’re not as angry against the patient’s body,” Hacker said. “We also think it suppresses the way the autoimmune system attacks the nerves.
“One of our goals is to determine in acceptable animal models whether BBR is significantly less cardio-toxic than mitoxantrone as a treatment for MS.”
Hacker said BBR3378 was found to be effective in animal models for treatment of another autoimmune disease, myasthenia gravis.
Hacker’s colleagues on the project are Dr. William Gunning, Dr. Boyd Koffman and Dr. Anthony Quinn.Dr. Kenneth Muldrew, assistant professor of pathology, UT Medical Center — “Non-Invasive Early Detection of Kidney Transplant Rejection Via Next-Generation Sequencing”
Physicians at UT Medical Center performed 57 kidney transplants between June 30, 2010, and July 1, 2011.
Of those, statistics predict that at least five failed due to patients’ rejections of the new kidneys.
“Renal allografts have a failure rate of 10 percent in the first year, despite advances in immunosuppression,” Muldrew said. “Because the patient and the donated kidney have different levels of tissue compatibility, tissue matching increases the odds of a successful transplant, but rejection is a constant threat.”
Present tests, he said, detect problems when rejection already is occurring. With sophisticated instrumentation that’s been on the market for only 18 months, Muldrew aims to discover signs of rejection at earlier stages and potentially save patients and their donor kidneys through “next generation” DNA sequencing.
“The next-generation equipment will allow us to sequence very large amounts of DNA in a patient’s sample,” Muldrew explained. “The patient’s DNA is different from the transplanted kidney DNA. With this technology, we can measure the relative amounts of transplanted kidney DNA within the total amount of DNA. Over time, we hypothesize this test will be much more sensitive than traditional tests for rejection.”
The equipment also will allow sequencing of the major histocompatibility complex, which determines compatibility of donors for organ transplant and susceptibility to autoimmune disease.
“The challenge that we will have is that once you get this huge amount of information, what do you do with it all?” Muldrew asked. “It’s incredibly exciting how far genetic sequencing has progressed in the last 10 years.”
Members of Muldrew’s research team are Dr. Anthony Comerota (collaborator, Promedica Jobst Vascular Institute), Dr. Jennie Lovett and Dr. Michael Rohs.Dr. Kam Chi Yeung, associate professor of biochemistry and cancer biology, UT Medical Center — “A Micro-RNA Connection in BRafV600E-Induced Melanomagenesis”
If you’ve ever wondered how a spot on your skin can change from a simple aberration to melanoma, or skin cancer, you’re in good company.
Yeung’s project will examine the BRAF gene and its protein, BRaf, which is responsible for the survival and proliferation of cells. Both are key components in the development of melanoma, with approximately 60 percent of cases involving a BRAF mutation, according to Yeung. Paradoxically, the identical mutation in BRAF also occurs in benign nevi (mole) with similar frequency.
Yeung and his team will gather hundreds of melanoma tissue samples from area physicians and conduct tests on BRAF genes. Of particular interest is the unpredictability of the mutated gene.
“Your body is wired to prevent cancer, but when the DNA in a cell changes, a previously healthy cell can become cancerous,” Yeung said. “Activation mutations in the BRAF gene are found in several types of cancer, including melanoma.
“We’ll try to understand the big difference in BRAF mutations,” Yeung said. “Some become cancerous and some become just a mole on the body. Why are there two such different consequences after mutation?”
Skin cancer is the most common form of malignancy in the United States, with about 3.5 million skin cancers in more than two million people diagnosed annually, according to the Skin Cancer Foundation.
Drs. Michael McPhee, Mounir Boutros and Amy Lynn of ProMedica Cancer Institute are partners with Yeung on the project.
The researchers agree that funding from the Translational Research Stimulation Award program is vital to their projects.
“With the current environment, it’s very difficult, very competitive, to get funds for these types of studies,” Yeung said. “It becomes a chicken-egg situation; where do you get the data without initial exploration?”
“Many organizations that award grants want you to have research and data already,” Muldrew added. “Without the seed funding to do some of that work, you won’t be able to compete with others vying for the same grant money. For a relatively new faculty member such as myself, seed money is crucial.”