By David Simpson
A passerby might not give a second thought to the brick-and-glass building at 4211 Monarch Way. There is little hint of the high-stakes work going on inside.
But here, in 麻豆国产AV's Innovation Research Park, Professor Richard Heller and his colleagues at the Frank Reidy Research Center for Bioelectrics are making breakthroughs in therapy for cancer and other diseases.
They're doing so with the aid of a machine that can generate extremely rapid pulses of electric power. When directed at a tumor, those pulsed electric fields can penetrate cell walls and deliver chemical therapy or DNA, or even directly destroy the tumor.
That's not all. The researchers have produced a strong immune response in mice - not only against the treated tumor but also against untreated ones. Aspects of this technology have been shown to be effective in human clinical trials as well.
Heller will talk about this and other promising work at the next Provost's Spotlight, from 3:30 to 5 p.m. March 21 at University Theatre. Admission is free.
The Center for Faculty Development reached Heller for an email interview ahead of the event.
What got you interested in medicine?
The question of what causes illness and how to find ways to be able to effectively treat disease.
What appeals to you about research?
Finding answers to problems. Being able to solve difficult questions and determine how something works or to discover something that was unknown. Finding ways to do things that were not thought possible.
What brought you to 麻豆国产AV and the Frank Reidy Research Center for Bioelectrics, and what has your role been?
I had been working on applications of pulsed electric fields at my previous institution and had met Karl Schoenbach and Stephen Beebe [both of the Reidy Center] and was aware of their work. While I was working in the micro-millisecond range of pulses, they were demonstrating the effectiveness of nano-picosecond pulses. I thought it was a good opportunity to join a cluster of researchers that were doing research focused on biological effects of pulsed electric fields. I would be able to add additional aspects and expand the Center for Bioelectrics. When I joined the Center for Bioelectrics in July, 2008, it was as Executive Director. I was asked to expand and double the size of the center. When I arrived, we were eight faculty and about 20 people. During my seven years as director we grew to 18 faculty and over 70 people (faculty, post-docs, students, technicians and support staff) working at the center. Our research expenditures from external funding have grown from around $900,000 in June 2008 (just prior to my arrival) to currently around $5.5 million. I stepped down as Executive Director in August 2015, and I am currently Professor and Eminent Scholar.
What is 麻豆国产AV's reputation in bioelectrics research?
The Frank Reidy Research Center for Bioelectrics is currently the global leader in the field of bioelectrics. Advancements in this area rely heavily on the intersection of the physical and biological sciences. CBE has made these significant contributions because it is able to bring together multiple disciplines to focus on the interactions between pulsed electric fields (picosecond to millisecond) and biological cells and tissues. Researchers from around the world working in this field and related fields look to the Center for Bioelectrics for leadership and to find out the latest breakthroughs in this research area. CBE is a symbol and leader for the field of bioelectrics, but because the researchers at the center have made major contributions in so many areas, such as cancer, cardiopulmonary, wound healing, etc., the impact goes well beyond the area of bioelectrics. 麻豆国产AV CBE belongs to the International Consortium for Bioelectrics, was one of the three founding members and is the coordinating center. Currently there are 16 centers from around the world that belong to the consortium.
Describe how pulsed electric fields are being used in medical research at the center.
There are multiple approaches for utilizing pulsed electric fields in medical research. The two major categories are to use short pulses in the microsecond to millisecond range and ultrashort pulses in the nanosecond to picosecond range. The ultrashort pulses (nano-picosecond pulses) are predominantly used to have direct effect on cells. These pulses can be used to stimulate or activate cells, such as stimulating nerve cells or activating cells or platelets. These ultrashort pulses can also induce cells to undergo cell death, which can be utilized as an effective means of killing cancer cells or to ablate specific tissue that is not functioning properly. These pulses can be utilized for cancer therapy, wound healing, cardiac applications and potentially neuro stimulation. The short pulses (mico-millisecond pulses) are predominantly used to deliver drugs or genes to cells. The pulses can temporarily permeabilize cell membranes to allow molecules access to intracellular spaces. Utilizing this approach, these pulses can be used for a variety of biomedical applications such as cancer therapy, whether by delivering chemotherapeutics at low doses to avoid toxicity or by utilizing plasmid DNA encoding genes that will produce immune-stimulating molecules to have a systemic effect. They can be used in cardiovascular applications to treat coronary artery disease or peripheral artery disease by delivering DNA encoding molecules that will induce blood vessel growth. They also can be used to deliver agents that will enhance wound healing. The short pulses are also quite effective at delivering DNA vaccines, which for some targets have distinct advantages over vaccines utilizing recombinant proteins.
Describe your current research, and the results you've seen.
The major focus of my research is to develop in vivo delivery procedures for non-viral gene therapy. My research group has developed new protocols or devices that are being tested for potential therapies for cancer, wound healing and vascular diseases (peripheral and coronary ischemia), as well as vaccine and immunotherapy protocols. We have made critical breakthroughs that have enhanced the progress of the use of pulsed electric fields for biomedical applications. In cancer, we developed a protocol to effectively deliver a plasmid encoding interleukin-12 directly to solid tumors. IL-12 is a potent cytokine that is very effective when delivered at the right dose to stimulate a strong immune response against the treated tumor, as well as untreated tumors. This protocol was successful in clinical trials, eliminating disease completely in several late-stage melanoma patients. It has now been combined with another immune-stimulating agent to further enhance its effectiveness. Response rates close to 50 percent have been observed, and the approach is now being tested in a registration trial, which is the final step prior to FDA approval. My group is also evaluating other devices and protocols to deliver agents to the skin to be able to develop an effective means of delivering DNA vaccines as well as to test a possible means to develop a protein replacement therapy for diseases such as hemophilia B. Finally, we are also working on ways to effectively deliver genes directly to the heart as a means to treat coronary artery disease and to prevent or repair infarcts.
Where does your research go from here, and what are your hopes for it?
There are many possible directions for the research. This area has seen tremendous growth, and there are many more researchers entering the field and utilizing the technology. I think there will be many advances. For my specific research, I am focusing on how to further advance cancer therapy. I believe that we can further augment the immune response, bring down costs of the therapy and make it available to more people. I am also very excited about the possibilities of moving our skin delivery technology to the clinic as possible treatments for a variety of illnesses. We are developing some cutting-edge approaches that I believe will have a significant impact. My hope is to start seeing these technologies and treatment protocols gain FDA approval and begin to be used on a regular basis. This is not too far away, and I believe once the first ones are approved others will not be far behind.
The Provost's Office and the Center for Faculty Development invite the University community to come out and meet Richard Heller at the Provost's Spotlight on March 21. Refreshments will be served after the event.