Joseph R. Testa, PhD, FACMG

Fox Chase Cancer Center

Professor/Senior Member, Cancer Prevention and Control Research Program
Carol & Kenneth E. Weg Chair in Human Genetics
Chief, Genomic Medicine
Director, Clinical Cytogenomics Laboratory 

Joseph R. Testa, PhD, FACMG, has had a long and storied career focused on mesothelioma and other forms of cancer, much of it spent at Fox Chase Cancer Center in Philadelphia, where he has been since 1989. His research interests include the molecular biology of mesothelioma and factors that may predispose patients to it, the role of AKT in oncogenesis, and the use of genetically engineered mice to further his work.

The Testa lab investigates the role of hereditary and somatic mutations in malignant mesothelioma. The group discovered frequent mutations of the CDKN2A locus — a region of DNA that encodes the tumor suppressors p16INK4A and p14ARF — and NF2 in human mesothelioma. In 2011, he and his collaborators also discovered germline mutations of the BAP1 tumor suppressor gene in families with a high incidence of mesothelioma, the first study demonstrating that inherited mutations can influence a person’s risk of mesothelioma.

Besides mesothelioma, some BAP1 mutation carriers were found to develop ocular melanoma or other cancers. This discovery, along with concurrent work by two other groups focusing on other tumor types, led to the what is now referred to as the BAP1 tumor predisposition syndrome (BAP1-TPDS). Individuals with this syndrome, who carry heterozygous BAP1 mutations, are at high-risk for the development of a variety of neoplasms, including benign melanocytic tumors, as well as several malignant tumors, including malignant mesothelioma, ocular and cutaneous melanomas, and other cancer types such as renal cell carcinoma and meningioma.

Subsequently, Testa led an international study that identified a mutated gene called LRRK2 that may predispose to mesothelioma. His lab also found that expression of LRRK2 was downregulated in a majority of mesotheliomas from a series of unrelated patients, suggesting that loss of LRRK2 expression is a newly recognized tumor suppressor alteration in this disease. He also published research indicating that the presence or absence of the receptor-interacting protein kinase 3 (RIPK3) can help determine the effectiveness of drugs in cases of mesothelioma.

More recently, he has taken advantage of his mouse models to conduct preclinical studies with chemoprevention agents and novel molecularly targeted therapies. Long-term testing of serum marker levels is also continuing in human BAP1 mutation carriers and in individuals exposed occupationally, the latter facilitated by a longstanding, close working relationship with a local asbestos workers union.

In 1991, he co-authored a seminal paper that revealed that although the viral and human genetic sequences coding for the AKT protein were similar, there were some important differences in the viral sequence that made the protein for which it coded continuously active and gave the cell better survival ability.

The reason this finding was so significant is that the AKT protein is important in shutting down processes such as chemotherapy that kill abnormal cancer cells. Because viral-derived AKT is continuously active and the human form is not, the scientists realized that the human form must have additional influences such as growth factors to activate it. Once activated, AKT appeared to be extremely important in tumor formation. Testa’s group subsequently cloned the AKT2 protooncogene and provided the first evidence for its recurrent involvement in human cancers.

Several years ago, Testa conducted a search and found that more than 50,000 papers have been published that include AKT in the title or abstract. The subsequent research has demonstrated that among other important properties, AKT is activated in many different tumor types, including prostate, breast, lung, ovarian, and pancreatic cancers.

Testa received his doctorate in biological sciences from Fordham University and was a postdoctoral fellow at the University of Chicago. He was made a Diplomate (Clinical Cytogenetics) by the American Board of Medical Genetics in 1987 and was a Founding Fellow PhD of the American College of Medical Genetics and Genomics (FACMG) in 1993.

He is a member of a number of professional organizations, including the American Association for the Advancement of Science, the American Association for Cancer Research, and the International Mesothelioma Interest Group.

His other distinctions include a number of honors and awards, including the Pioneer Research Award from the Mesothelioma Applied Research Foundation, the Wagner Medal from the International Mesothelioma Interest Group, the Reimann Honor Award of the Fox Chase Cancer Center, and the Irving Selikoff Award for Cancer Research. He is also an elected Fellow of the American Association for the Advancement of Science.