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Graham S. Timmins, Ph.D. — 2013 STC.UNM Innovation Fellow

2013The inventor we honor as the 2013 STC.UNM Innovation Fellow, Dr. Graham S. Timmins, is using his ingenious ideas to fight infectious diseases and the deadliest form of skin cancer by creating better drugs and faster ways of detecting infection and melanoma. Dr. Timmins is an Associate Professor in the College of Pharmacy’s Department of Pharmaceutical Sciences. Trained in biochemistry, his expertise is in the area of medicinal chemistry, a multidisciplinary science that combines synthetic organic chemistry, pharmacology and other biological specialties to design and develop drugs for the treatment of diseases. His areas of research focus on using stable isotope-labeled compounds in developing new drugs and diagnostics and on studying free radical biology in melanoma and infectious disease. Free radicals (in chemistry that is, not politics) are molecules with unpaired electrons, which makes them highly chemically reactive. In biology systems, free radicals regulate many processes and are involved in the metabolism of biological compounds. Dr. Timmins has applied his expertise in these areas to designing and developing a variety of new drugs and tests for diseases that are complex and whose processes are still only partly understood. Tuberculosis, with its many evolving forms (active, latent and drug resistant) is a good example. As Dr. Lynda Welage, Dean of the College of Pharmacy, explains: “Whether it is tuberculosis, infection with P. aeruginosa or melanoma—the three things all of these diseases have in common is that they are (a) difficult to diagnose and treat; (b) kill many patients each year; and (c) we have not as yet identified “ideal” diagnostic and treatment strategies. Dr. Timmins is working towards identifying better/ideal strategies for these difficult conditions.”

One way he’s doing this is through his innovative breath-test technologies, currently being developed for diagnosing and monitoring cystic fibrosis, ventilator-associated pneumonia and tuberculosis infections. Test results are available within 10 minutes of inhaling a tracer compound (urea) made from a non-radioactive carbon isotope. (Isotopes are variants of a main chemical element and are used because they are easy to measure.) The pathogen breaks down the urea into carbon dioxide, which can be detected in the patient’s exhaled breath. The breath test samples the entire lung non-invasively and can rapidly diagnose, in cystic fibrosis patients for example, the onset of first infection by chronic P. aeruginosa and monitor its conversion to a mucoid, drug-resistant strain. The ability to quickly pinpoint first infection and monitor whether prescribed drugs are working is critical to delaying the conversion of P. aeruginosa to its mucoid strain, since conversion leads to the lung damage that causes progressive disability and a shortened life span for these patients. The breath-test technologies led to the formation of local start-up Avisa Pharma in 2010. Co-founding the company with Dr. Timmins, President and CEO David Joseph remembers their initial meeting: “I had the opportunity in 2010 to review the STC life science portfolio for licensing. Of all the ones reviewed, Graham’s technology attracted me the most. It is very clever, innovative, and addresses a big need, and meeting Graham was key since the entrepreneur and the scientist must have ‘chemistry’ and rapport and we hit it off immediately.”

Dr. Timmins has also developed technologies that improve the efficacy of the tuberculosis drug isoniazid. Isoniazid is an antibiotic that has been used to treat active and drug-resistant strains of tuberculosis since 1952. After several years of studying how isoniazid is activated and changes to a free radical, Dr. Timmins has discovered in the lab that the drug can be rendered more potent against the pathogen by using its isotopically labeled derivatives in combination with a low strength magnetic field. The goal is to use this new drug to treat multiple drug resistant (MDR) and extremely drug resistant (XDR) tuberculosis. The World Health Organization estimated that, in 2010, 440,000 new cases of MDR tuberculosis and 40,000 new cases of XDR tuberculosis were diagnosed in developed countries (North America, Europe, Japan and Australia) with enormous treatment costs. His tuberculosis technologies have received two gap-fund awards from STC’s gap-fund program.

On the skin-cancer front, Dr. Timmins is applying original thought to melanoma research. Melanoma has one of the fastest growing cancer rates and is the most deadly form of skin cancer. The National Cancer Institute estimated that in 2012 76,000 people would be diagnosed with and 9,000 die from melanoma in the United States alone. New Mexico has some of the highest rates of melanoma in the U.S. It is becoming one of the most common cancers among younger adults. It is the leading cause of cancer death in women aged 25-30 and is second to breast cancer in women aged 30-34.

Sunlight is composed of visible light that we can see and ultraviolet (UV) light that we cannot see. The two types of UV light are UVA and UVB. UVA light tans the skin and UVB sunburns the skin. Both damage the skin and can contribute to skin cancers. Melanoma occurs when melanocytes, one of the two major types of skin cells, divide and grow in abnormal ways. Dr. Timmins has believed for years that UVA is likely a major cause of melanoma. He has made significant contributions to the field using electron paramagnetic resonance (EPR) spectrometry to explore how UV light affects melanin (skin pigment) and leads to the formation of melanoma, research that is helping to solve a 30-year controversy over which UV wavelength is responsible.

His platform technology uses an EPR technique to measure a Sun Protection Factor (SPF) that is weighted to the melanocyte, and also is used to study the wavelength dependent activity of sunscreens. The new factor, called “Melanoma Protection Factor” or MPF®, classifies cosmetic and dermatological sunscreens, as well as clothing and fabrics, by assigning a broad spectrum number which is a measure of both UVA and UVB protection, as opposed to an SPF that measures only UVB. STC has been granted a registered trademark for MPF®, which has many applications for the sunscreen industry. The technology also has great value for the sunscreen industry because of new FDA regulations for a UVA-protection rating system that officially went into effect on June 18, 2012. More good news from a study published in the June 2012 edition of the journal Nature is confirming the research underlying Dr. Timmins’ technology. Entitled “Melanoma Induction by Ultraviolet A But Not Ultraviolet B Radiation Requires Melanin Pigment,” the study showed that UV-induced melanin formation was shown to be directly involved in melanoma formation in mammals. The study also showed that UV induction of melanin, as a melanoma-causing agent, works when skin is exposed only to UVA and not UVB radiation.

The key to his success as an inventor is his practical approach and adaptability to solving problems. It is the core of his creative drive. If the diseases he studies are known for their ability to change, to adjust to different conditions and environments, well then that’s the approach he takes. “We work with existing drugs, changing the isotopic make-up, which is a faster route to new therapy than formulating new drugs,” he said recently in explaining his work.

It is astonishing what basic research can lead to. The path may be long in developing the new drugs and better treatments that make a real difference in the lives of countless patients who suffer from debilitating and deadly diseases but the end result is worth it. “The ability to detect bacterial lung infections early and quickly and monitor therapy daily will greatly improve patient outcomes, shorten hospital stays, and significantly reduce healthcare costs,” adds Avisa CEO David Joseph. Breath tests are shaping up to be the next innovation in non-invasive medical testing and Avisa’s breath test has the potential to be an enabling technology for lung diseases.

STC.UNM is proud to bestow this award on a university inventor who embodies the meaning of innovation in all aspects of his work. His research is focused on solving real world problems with creative solutions that translate into products and treatments that will improve the health of patients everywhere.