Dr. Houvras Arrives at Weill Cornell Driving ‘MINICOOPR’ on New Path for Treatment of Melanoma
August 12, 2011
Dr. Houvras and a few of the zebrafish
MiniCoopR consists of a transposon vector, a specialized piece of DNA sequence that integrates into the zebrafish genome, and a unique genetic strain of zebrafish that has been engineered to allow researchers to see melanoma. Although evocative of a small European car, Dr. Houvras’ transposon vector takes the name MiniCoopR from the first two words of its more detailed description, Minigene Cooperating Oncogene.
As described in their paper, Dr. Houvras and research partner, Dr. Craig Ceol of Harvard, used MiniCoopR to alter DNA to express genes linked with tumor development. In fact, they have discovered a gene that accelerates melanoma growth and is abnormally expressed in up to 70% of human melanomas.
While he researches the development and potential treatment of human cancer, Dr. Houvras makes use of the zebrafish as a model organism. Long-used in developmental biology, Dr. Houvras is one of a growing number of researchers who are using the zebrafish to model and understand the human cancer. Because of its genomic properties and relatively swift lifecycle, the zebrafish is an ideal organism for studying the development of human cancer. The zebrafish develops rapidly (the fish egg’s gestation period is only 3 days; the average adult lifespan is 2-3 years) allowing researchers to observe tumor formation and growth relatively quickly. And zebrafish produce hundreds of eggs in a clutch making genetic studies possible. Dr. Houvras explains that some model organisms, such as fruit flies and worms, are great for genetic studies, but they lack the organs of higher vertebrates.
“The zebrafish fills a key niche for model organisms because we can do genetic studies and we have most of the important tissues and organs that are present in humans. Most importantly, when human cancer is introduced into zebrafish cells, the cancer grows in the same way in the fish as in humans; samples from tumors in the zebrafish and tumors in humans can appear strikingly similar under the microscope.”
Weill Cornell - A Supportive Home for a Physician-Scientist and a Zebrafish Researcher
Dr. Houvras spent five years as a fellow at Boston Children’s Hospital in the lab of one of the leading zebrafish researchers, Dr. Leonard Zon. At Weill Cornell, Dr. Houvras has found a home as a physician-scientist, working primarily in the laboratory--but also seeing patients. ”Weill Cornell has provided a very supportive environment here for the kind of research I want to do.“ Dr. Todd Evans, Professor of Surgery, led Dr. Houvras’ recruitment to Weill Cornell. As a fellow zebrafish researcher, Dr. Evans convinced Dr. Houvras that Weill Cornell could satisfy the “unique set of needs” zebrafish research requires.
Zebrafish Update: Every Eight Hours
This zebrafish was featured on the cover of Nature
Drs. Houvras and Evans operate state-of-the-art labs for the study of zebrafish in development and as a model organism for studying cancer biology. In their zebrafish facility, zebrafish are bred and fed by specially trained technicians. Zebrafish development begins in petri dishes, then after hatching, the tiny fish are introduced into small fish tanks. Far more sophisticated than an aquarium, 2,400 tanks of various sizes are tended to by custom-built electronic equipment that cycles water, monitors pH, temperature, and water quality -- it also emails status updates to Dr. Houvras and his staff every 8 hours. A healthy environment for the zebrafish to grow and thrive during their 2-3 year lifecycle is ensured.
In his clinical practice at Weill Cornell, Dr. Houvras specializes in the treatment of thyroid cancer and other endocrine cancers. ”The ultimate goal of the research is to achieve better treatments for our patients and to develop cures for these diseases,“ he says.
Which Genes were Driving Tumor Formation and Growth?
Dr. Houvras and colleagues used zebrafish to solve a vexing problem in cancer biology. Melanoma, like other solid tumors, is characterized by changes in the DNA. There are many regions of the genome that are amplified, leading to the overexpression of hundreds, even thousands, of genes. Dr. Houvras used MiniCoopR to test genes from one interval on chromosome 1 that is recurrently amplified in human melanoma.
“MiniCoopR showed us that only one gene in this interval accelerated melanoma in zebrafish,” he notes. The study was leveraged to take advantage of the zebrafish’s breeding ability�more than 3,000 transgenic animals were studied in order to discover SETDB1. Zebrafish were observed and tracked in a specialized database. Researchers recorded which fish developed cancer and when they developed the earliest visible lesions. By studying thousands of fish they found that SETDB1 expression led to a unique cancer phenotype.
“We found that SETDB1 dramatically accelerates cancer in a model organism. It would have been very hard, maybe impossible, to perform this study in other model organisms, such as the mouse,” says Dr. Houvras. Because SETDB1 is overexpressed in 70% of metastatic melanomas, it is a logical target for new cancer drug development. In his own laboratory at Weill Cornell, Dr. Houvras plans to continue to use zebrafish and MiniCoopR to discover new cancer causing genes in melanoma and other solid tumors.
For More Information
Dr. Houvras’ article in Nature
More information about the Zebrafish - the Zebrafish Information Network