Michael A. Barry, Ph.D.
- Primary Appointment
- Infectious Diseases
- Joint Appointment
- Molecular Medicine
- Academic Rank
- Professor of Medicine
The laboratory of Michael A. Barry, Ph.D., is working to use genes and viruses to treat a set of very difficult diseases. Because these agents are as adaptable as DNA itself, Dr. Barry and his team can apply these "drugs" against a variety of diseases by fine-tuning which cells they target and avoiding or activating the immune system. This work falls into three areas: gene therapy, gene-based vaccines and anti-cancer virotherapy.
- Gene therapy. For many genetic diseases, it is known which genes are defective. The challenge is to efficiently and safely replace these defective genes with their functional counterparts. Dr. Barry's lab works primarily on gene therapy for two types of genetic diseases: Duchenne muscular dystrophy and propionic acidemia. One affects muscle and one affects every cell in the body. They therefore represent two very different therapeutic goals for gene therapy. Both diseases have devastating consequences for children. Both types of gene therapy are poised for translation into the clinic.
- Gene-based vaccines. Vaccines are one of the most cost-effective medical interventions available. Most vaccines that you receive consist of inactivated or damaged versions of the pathogen. While these traditional approaches can be potent, they have not been able to control some of the most devastating infectious agents, so other approaches are needed.
In this case, Dr. Barry's lab is also using genes as drugs. However, instead of trying to fix a defective gene, they are actually delivering single genes from pathogens to vaccinate against them. Because only a subset of pathogen genes are used, gene-based vaccines avoid the risk of infection from live vaccines while mimicking a real infection and the protection that occurs from it.
Dr. Barry's work in this area is focused on two dangerous pathogens: HIV and the "superbug" drug-resistant Staphylococcus aureus (MRSA). For HIV, he and his group are working to provide a simple oral vaccine that can be swallowed and repel the virus at its early sites of entry into the body before it destroys the immune system. For drug-resistant pathogens such as MRSA and tuberculosis, they have developed vaccines that attack antibiotic resistance with the hope of "devolving" these pathogens back to forms that are susceptible to older antibiotics.
- Anti-cancer viruses. For gene therapy and vaccines, Dr. Barry and his colleagues want to deliver genes to cells and have the cells survive. For this reason, they use tamed versions of viruses to deliver genes for gene therapy or gene-based vaccines. For cancer therapy, the goal is to kill cells. For this application, they modify the viruses to still kill cancer cells, but protect normal cells. These anti-cancer viruses have the appeal that they can be thought of as "self-amplifying" drugs because each cancer cell that gets killed can in turn produce thousands of new anti-cancer viruses that can spread to other cancer sites. Therefore, these self-amplifying drugs can infect one cancer site and spread. Dr. Barry's lab therefore hopes they may be useful to treat cancers that have spread or have metastasized locally or throughout the body.
In recent years, the lab has tested a number of viruses against many types of cancer, including prostate, breast, ovarian and B cell cancers. Interestingly, they have found that different viruses actually appear to have different "appetites" for killing different types of cancers. Based on this, the lab is moving several viruses toward the clinic, with viruses for prostate cancer and B cell lymphoma being closest to clinical translation.
Significance to patient care
The work of Dr. Barry and his team on gene therapy addresses diseases that have no other treatment options, so advances in this area are likely to greatly improve the quality of life and survival of these children and adult patients.
Infectious diseases are one of the greatest worldwide causes of death in humans. Dr. Barry's work targets vaccines against pandemic infectious diseases, so progress in these efforts holds promise to prevent these diseases before they happen.
Metastatic cancer is a profound challenge to current treatments. The lab's efforts to deliver "self-amplifying" virotherapy holds promise to attack disseminated cancer, providing another weapon in the arsenal of treatment options for patients.
See my publications
Post Graduate Trainee
Mentor: Stephen A. Johnston
Department of Medicine, University of Texas Southwestern Medical Center
Mentor: Alan Eastman
Department of Pharmacology and Toxicology, Dartmouth College
Department of Chemistry, Nebraska Wesleyan University