Kyle Chamberlain, Ph.D.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic disorder that predominantly affects the right ventricle of the heart. ARVC is a progressive disease and a frequent cause of sudden cardiac death during exercise. ARVC is in most cases inherited in an autosomal dominant fashion due to haploinsufficiency in one of the desmosomal genes such as plakoglobin, plakophilin 2, desmoglein 2, desmoplakin and others.

In collaboration with Dr. Ali J. Marian’s group at the University of Texas Health Science Center, Dr. Chamberlain is developing adeno-associated virus (AAV)-based approaches to treat ARVC. Because of the limited packaging capacity of AAV, which is approximately 5kb, one of the desmosomal proteins associated with ARVC, desmoplakin, cannot be delivered by a single AAV vector. Dr. Chamberlain is actively pursuing novel approaches to deliver desmoplakin with a novel two-vector system.

Firas Elmastour, Ph.D.

Efficient delivery of therapeutic transgenes remains the single most important roadblock to the successful translation of gene therapy to the clinic. While AAV vectors are among the most promising gene transfer platforms, efficient gene delivery with AAV vectors remains challenging. In fact, recent results of a clinical trial aimed at the treatment of heart failure with a vector delivering the sarcoplasmatic calcium ATPase, SERCA2a, with an AAV vector failed to achieve its primary and secondary endpoints, purportedly as a result of inefficient gene delivery with AAV serotype 1. Whereas this apparent inefficient gene delivery might possibly be overcome by different delivery approaches or higher vector doses, the isolation of AAV variants with high tropism for human cardiomyocytes remains an important area of research.

Dr. Firas’s project is aimed at isolating such variants using directed evolution. He focuses particularly on the production of AAV capsid libraries with improved properties and complexities.

Ananda Mookerjee, Ph.D.

In developed countries, ovarian cancer is the gynecological malignancy with the highest rate of mortality and the 5th most common cause of cancer-related death in women. Clearly, current standard of care approaches to treat this devastating disease are unsatisfactory and conceptually different therapeutic modalities are sorely needed. Immunotherapy shows great promise for the treatment of an array of cancers, including ovarian cancer. Unfortunately, our knowledge of tumor-specific antigens is limited, which hampers the successful application of a number of immunotherapeutic approaches.

Dr. Mookerjee’s project is aimed at the development of an immunotherapeutic approach that does not rely on prior knowledge of tumor antigens. If successful, this approach has the potential to open a completely novel line of attack to treat ovarian cancer as well as other cancers.