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Q&A with Zheng-Rong Lu

Zheng-Rong Lu, who joined Case Western Reserve University in 2009, is the M. Frank Rudy and Margaret Domiter Rudy Professor of Biomedical Engineering and heads the Case Center for Biomolecular Engineering. Cutting-edge research conducted by Lu’s group was highlighted in two journals last spring — the June 16 issue of Molecular Therapy – Nucleic Acids and the April issue of Bioconjugate Chemistry. 


What is the primary focus of your research in the Case Center for Biomolecular Engineering?
I am a chemist by training, so most of my work is associated with biomolecules. We design biomolecules for disease diagnosis and therapy, depending on the application.

Can you describe the gene delivery system you designed that is the focus of the article in Molecular Therapy – Nucleic Acids?
Gene delivery is still a big challenge for gene therapy, which has been around for over a half century. If somebody has a genetic disorder or disease, we can introduce a normal gene to replace the abnormal gene. Then we have a chance to cure the disease. The problem is how to deliver a normal gene into the right place – the right cells – and also not cause any unintended problems.

Most people use viruses, which work very well but have many other issues, including safety. We are trying to do something different. We’ve developed some simple, smart biomolecules that can help to deliver genes into the right places. In the research featured in Molecular Therapy – Nucleic Acids, we tried to deliver genes to the eyes to cure some monogenic eye disorders. We showed the therapeutic efficacy of the system in a mouse model in this study. It seems safe and won’t cause some of the other problems of viral systems.

What’s the next step for that project?
Ideally, we will move forward with clinical translation. We have a patent filed and are trying to obtain funding for translational development. Also, we’d like to extend this technology to treat some other genetic disorders in the eyes, like Stargardt disease. So the application is really broad. If we can make a breakthrough in one disorder with the system, it will have the potential to be useful for many other related diseases.

Can you talk about your research on a system to non-invasively identify prostate tumors harboring cancer cells that’s highlighted in Bioconjugate Chemistry?
In clinical cancer management, one big challenge is to detect cancer at an earlier stage. Then, once it’s detected, doctors want to know whether the cancer is malignant — whether it has the potential to metastasize to some other part of the body — or benign. Biopsy is still the most used method today to differentiate between malignant and benign tumors, but it’s not very accurate. If you don’t sample in the right location, you may get wrong information.

There’s a huge clinical need for something simple and non-invasive to detect cancer at a very early stage and also to differentiate aggressive tumors from benign ones. We try to approach this based on our understanding of cancer biology. We’ve identified a marker associated with tumor metastasis and drug resistance. We have developed a probe so we can image that protein. The probe is able to detect and identify aggressive tumors based on expression levels of the protein, which relates to the tumor aggressiveness. We’ve demonstrated the concept and validated the feasibility. It shows great promise.

And wouldn’t knowing how aggressive a tumor is aid clinicians tremendously in deciding treatment options?
Absolutely! That’s the key in cancer management and tailoring precision therapy for better treatment outcome. It is the advantage of the technology that we are working on. We have designed this technology based on our understanding of cancer biology of the biomarker, which shows strong clinical relevance. We have started the FDA-required safety evaluations and hope to start a clinical trial soon.

Ultimately, what are the translational benefits of your work on differentiating the aggressiveness of tumors?
Once cancer is diagnosed, it’s often treated aggressively — even some of the cancers that aren’t life-threatening. The problem is we can’t accurately differentiate the aggressiveness of tumors, so everybody is treated aggressively. If you can differentiate aggressiveness, doctors will design different approaches to treat different types of cancers. This may eliminate unnecessary procedures and spare a large number of patients from invasive procedures, thereby reducing the cost of healthcare.

Multidisciplinary work is key to advancing these kinds of solutions. What cross-disciplinary partnerships do you have?
I have several collaborations across the campus and in the local medical community. We collaborate with other biomedical engineers in the Case School of Engineering, as well as basic scientists in the School of Medicine and in the Case Comprehensive Cancer Center. We also collaborate with physicians from University Hospitals and Cleveland Clinic. Without these partnerships, it would be very hard to do the things we’re doing now.