Pathology and Laboratory Medicine
Weill Cornell Medicine
We have discovered that bone contains several distinct groups of stem cells, each of which has starkly different functions during health and disease. We propose that some of these stem cells will promote bone destruction and tumor growth in the setting of skeletal metastases, whereas others will play protective roles. The Pershing Square Sohn Prize will enable us to identify which of these stem cells enable cancer to destroy bone and thereby develop new strategies to prevent fractures and disability in cancer patients.
Matt Greenblatt, MD, PhD, is a physician scientist who leads a research program discovering new stem cells in the skeleton and understanding how these stem cells support the growth and bone destruction capacity of skeletal metastases. After completing an MS/BS program at Yale University, he then performed MD and PhD studies at Harvard University, completing his PhD in the laboratory of Dr. Laurie Glimcher. Receiving a NIH Director’s Early Independence Award and a Burroughs Wellcome Career Award for Medical Scientists allowed him to transition directly to establishing a research lab after completing residency in pathology at Brigham and Women’s Hospital. Currently he is an Assistant Professor in the Department of Pathology and Laboratory Medicine at Weill Cornell Medical College. Highlights of his work include identification of SLIT3 as an angiogenic factor driving bone formation and discovery of the stem cell on the outer surface of bones. In addition to his research, he serves as a pathologist at New York Presbyterian Hospital.
Targeting skeletal stem cells to treat tumor-induced osteolysis
Many forms of cancer are able to spread to bone, and this tumor growth in bone causes pain and skeletal fracture that are major contributors to the decreased quality and length of life associated with these cancers. Current treatments cannot prevent many of the complications associated with the presence of cancer in bone. Our research team at Weill Cornell Medicine recently reported that bone contains many previously unknown groups of cells, each of which is programmed for different functions.
“The Pershing Square Sohn Prize will allow us to show that tumors actively shape the pool of bone cells to expand those that promote bone destruction and fractures. Ultimately, this will lead to new approaches to counteract these tumor driven changes in bone cells and reduce the disability and death caused by tumor-associated fractures.”
This project’s central hypothesis is that only some of these new groups of skeletal cells participate in the tumor growth in bone and the ability of tumors to destroy bone. Tumors then have a “vested interest” in shaping the bone cell types present to favor those that promote their own survival and bone destruction. We will prove this hypothesis by using genetic mouse models to evaluate how each subset of skeletal cells support tumor-mediated cell growth and bone destruction. This work will establish a new paradigm for how tumors interact with bone, and will moreover change the direction of future drug development for treating cancer in bone towards developing agents that promote the growth of cells that make the bone inhospitable for cancer growth and bone destruction.
“Innovation is the product of having the resources and freedom to pursue your passion in science.”