ASU biochemist honored for lifetime achievement in improving human health
Sidney Hecht is director of the Biodesign Center for Bioenergetics at Arizona State University and a professor in the School of Molecular Science. Photo by Andy DeLisle/Knowledge Enterprise Strategic Marketing and Communications
By Luhnyae Campbell
When Sidney Hecht began his science career, biology and chemistry were typically viewed as separate disciplines that rarely interacted with each other. Hecht was one of the early scientists to recognize the important connections between the fields, devoting his career to using these connections to treat diseases and improve human health.
On Sept. 18, AZBio honored Hecht with the Arizona Bioscience Pioneer Award for Lifetime Achievement for his work merging biology and chemistry to understand, regulate and alter molecules and processes to improve human health.
Hecht is director of the Biodesign Center for Bioenergetics at Arizona State University. There, researchers work to improve diagnosis and treatment for diseases, particularly ones caused by defects in mitochondria — the tiny power plants in our cells that produce energy for our bodies. It is fitting, then, that Hecht is being honored during World Mitochondria Awareness Week, which takes place Sept. 16–22.
Hecht, who began publishing research studies as an undergraduate student, has extensive experience studying mitochondrial disorders and other molecular processes. He played a key role in the development of Hycamtin, a chemotherapy drug used to treat ovarian and lung cancer, as well as the study of the mechanism of the anti-tumor agent Bleomycin. Hecht — a professor in ASU's School of Molecular Sciences — is also the co-founder of Edison Pharmaceuticals, a company that develops treatments for inherited mitochondrial disorders.
In this Q&A, Hecht talks about the center’s successes and challenges.
Editor's note: Answers have been edited for length and clarity.
Question: What is the research focus of your center?
Answer: The Biodesign Center for Bioenergetics is focused on understanding the underlying molecular mechanisms of human diseases and developing and implementing strategies to treat patients with such diseases.
One major focus of our center involves mitochondrial disorders — the dysfunction of the organelle that produces most of our energy in the form of ATP. The disease of primary interest to us is Friedreich’s ataxiaAccording to the Friedreich’s Ataxia Research Alliance, people with this genetic, progressive and often life-shortening neuromuscular disease experience issues with balance and coordination of movement that lead to life-altering loss of mobility. Other common symptoms can include fatigue, serious heart conditions, scoliosis and diabetes., which is mainly a childhood disease.
More broadly, we study biological mechanisms, which may lead to new strategies at the research level and have the potential for therapeutic intervention. An example is the use of suppressor transfer RNAs, which can be used to modify protein structure and have the potential for correcting errors in protein structure associated with a number of rare disorders.
Q: What is the biggest challenge in this field of research?
A: Drug discovery and development is an extraordinarily complicated process that requires the skills of scientists and medical personnel with a broad range of expertise. Often, drugs are identified in academia or industry by the joint efforts of chemists and biologists focused on newly explored cellular pathways and mechanisms and the recognition of new strategies to address biological dysfunction.
Researchers then test the effects of promising new compounds using biological model systems, both in vitro (in the lab) and in vivo (in living organisms). Those that seem promising are studied for their physicochemical and biological properties in model systems and ultimately in clinical trials. These activities are quite time-consuming and very expensive. Prioritizing these efforts and expenditures is arguably the greatest challenge in drug discovery.
Q: What is something you consider one of the center’s biggest successes?
A: Mitochondrial respiration — the process that converts nutrients and oxygen into the energy source ATP — is essential to the proper functioning of mammals. Dysfunctional mitochondria can contribute to the progression of a number of human diseases. A critical mechanism in the mitochondrial respiratory chain involves a flow of electrons through protein complexes in the mitochondrial membrane.
We have succeeded in creating new compounds that can capture electrons which have leaked from dysfunctional respiratory chains and redirect them back into the respiratory chain, augmenting ATP production. One of these compounds is in clinical trials for the treatment of Friedreich’s ataxia, and others are being studied for the treatment of different diseases that progress in a related fashion.
Q: How are students involved in the center’s research?
A: In our center, the synthesis of compounds of interest as potential cytoprotective agents for mitochondria has been carried out almost exclusively by graduate students as part of their PhD studies. Recently an undergraduate has also been involved. The biochemical and biological evaluation of our newly synthesized agents has been carried out by several individuals, some of whom were undergraduates when the studies were carried out. A number of these undergraduates have since moved on to graduate or other professional studies.
Q: How does your research align with Biodesign’s mission of nature-inspired research?
A: Our research is designed to take advantage of the biochemical pathways employed by nature. In the case of mitochondrial therapeutic agents, we have focused on the use of functional analogues of alpha-tocopherol (vitamin E), which protects cells and their mitochondria from oxidative damage. By altering the structure of alpha-tocopherol, we have produced what we believe to be catalytic antioxidants, capable of much more potent activity than alpha-tocopherol itself.
Q: How did you become interested in science and, in particular, the field you are in?
A: My interest in science was initially based on learning what other scientists were doing. My specific interest in chemistry was inspired by a relative who was a graduate student in chemistry at the same time I was an undergraduate. I was especially intrigued to learn that one could make molecules that had never been made before and even have some idea of the way they might behave once prepared.
Q: What events set you on your research path?
A: The key events included my acceptance into the laboratory of Professor Stanley Tarbell while I was an undergraduate. I was successful in preparing a few key synthetic intermediates required for the structure elucidation and ultimate synthesis of the natural product fumagillin. I published my first two papers as a result of this experience.
Q: Describe your experience with Biodesign’s collaborative, interdisciplinary research culture.
A: As one who has collaborated throughout his career, I have noted an interesting facet of such interactions at Biodesign. Most of the external collaborations I have had involved joint efforts with others in which both parties contributed well-established skills to an extension of their ongoing efforts. In comparison, my most successful collaborations at ASU have been more broadly based and taken us into entirely new areas. I believe that this reflects Biodesign’s interdisciplinary research culture.
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