By analyzing key enzymes in a new way, an international team led by researchers at Weill Cornell Medicine has discovered how a well-known signaling molecule can either stimulate or suppress tumor growth depending on where it’s produced. The work, published Sept. 27 in Cell Reports, reveals a new aspect of tumor cell biology, and points to a promising strategy for treating many types of cancer. Cells use the small molecule cyclic AMP (cAMP) to trigger different effects largely depending on the proteins it activates. For example, past studies have shown that cAMP can either activate or suppress tumor growth under different circumstances. “Most people have studied cAMP by studying the effector proteins that [mediate its activity], or they've looked at the [enzymes that] inactivate it,” said co-senior author Dr. Jonathan H. Zippin, vice chair of research and an associate professor of dermatology and pharmacology at Weill Cornell Medicine, director of dermatology precision medicine at the Englander Institute for Precision Medicine, and a dermatologist at NewYork-Presbyterian/Weill Cornell Medical Center. Dr. Taha Merghoub, deputy director of the Sandra and Edward Meyer Cancer Center, the Margaret and Herman Sokol Professor of Oncology Research and a professor of pharmacology, as well as Dr. Elena Piskounova, an assistant professor of cell biology in dermatology, are also co-senior authors on the study. Instead of turning cAMP signaling on or off across the entire cell, as previous studies had done, Dr. Marek Drozdz, a postdoctoral associate in Dr. Zippin’s lab, wanted to activate cAMP in specific subcellular compartments. Two enzymes can produce cAMP in a cell: one bound to the plasma membrane and one that’s soluble. “We focused on the soluble one, because this source of cAMP could be targeted to different compartments within the cell, and then evoke a little pocket of cAMP signaling in each compartment,” said Dr. Drozdz, who is the lead author on the paper. To do…

Dr. Jedd Wolchok, an internationally acclaimed medical oncologist whose innovations in immunotherapy have revolutionized melanoma treatment, has been recruited as the Meyer Director of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, effective Sept. 12.

Using cutting-edge techniques, Weill Cornell Medicine and Memorial Sloan Kettering investigators have visualized the structure of a receptor targeted by an anti-cancer immunotherapy.