Dr. Bruce Stillman

From the eastern shore of Cold Spring Harbor and many vantage points on our beautiful campus, the emergence of a cluster of new buildings is now obvious. This exciting expansion of our research facilities flows naturally from the success of our current research and makes real a long-held dream.

A decade ago, the village of Laurel Hollow redefined our campus as a scientific and research zone distinct from its residential areas, clearing the way for potential expansion. A prior study of the Laboratory’s 113-acre (46 hectare) main campus had determined that any future development would leave open the fields to the north end of the campus and take place at the south end, close to existing buildings, to encourage scientific collaboration, By fall 2001, our Connecticut-based architectural firm, Centerbrook, had completed a vision for campus expansion that made efficient use of available space while retaining the “village of science” style that has come to define Cold Spring Harbor Laboratory. Now, because of the ingenuity of the Laboratory’s recent science, our need for that expansion is very pressing.

The dramatic success of our Cancer Center offers opportunities to turn our attention to novel therapeutic and diagnostic approaches to the control of human cancer. In recent years, our research staff has begun collaborating with clinicians in many cancer centers in the US and abroad. A number of new technologies developed at the Laboratory offer new approaches to diagnosis and treatment. One is the RNAi library developed in Greg Hannon’s laboratory, which makes it possible to turn off the expression of every human gene and thus identify those that, when inhibited, cause tumor regression or enhance the effects of chemotherapy. This approach will speed up the rate of discovery of new molecular targets for drugs against cancer cells.

Michael Wigler’s research group, in collaboration with Robert Lucito, has developed powerful techniques for identifying how many copies of a gene exist in each person. Classical Mendelian genetics taught us that we all have two copies of most of our genes but in 2004, Wigler, Jonathan Sebat and colleagues discovered that this idea is too simplistic. In our individual genomes we all have either missing genes or extra copies of genes, and the particular genes affected vary from one person to another. This new aspect of human genetic variation, referred to as copy-number polymorphism (CNP), has important implications. One is that CNP may contribute to an individual’s vulnerability to disease, an insight that has given fresh impetus to research on the genetics of autism, schizophrenia and neurodegenerative Parkinson’s disease. Another is that CNP may influence cancer cells. Cancer results from accumulated mutations in an individual’s DNA. Many of these mutations are copy number variations and with our new technology, they can now be quickly detected by scanning DNA taken directly from a tumor itself. This information will help physicians correctly identify the cellular origin of a tumor and decide on appropriate therapy, and help scientists identify potential new therapeutic targets.

Identifying potential targets is immensely valuable but validating them as effective is still a major challenge. One approach has been the study of hard-to-cure cancers in mice. Laboratory scientist Scott Lowe has been a leader in this area, pioneering new work on leukemias, lymphomas and liver carcinomas. Lowe has developed techniques for creating tumors in mice that contain combinations of genes that cause human cancers. This approach permits the discovery of new cancer-causing genes and also the testing of novel therapeutic strategies. For example, Lowe and Hannon have collaborated with Scott Powers to block tumor growth using RNAi molecules directed against genes that produce cancers. This mouse model is potentially powerful because anti-cancer drugs can be tested and validated in many combinations, something that is very difficult to do in human clinical studies.

The Laboratory’s development of these technologies, coupled with our strong program in understanding the biology of cancer, has fashioned a new path for cancer therapy research. Technology development has also opened additional possibilities in neuroscience.