Matthew Greenblatt, MD, PhD is a physician-scientist who leads a research program discovering new stem cells in the skeleton and understanding how these skeletal stem cells impact bone metastases, neurodegeneration, and neuroinflammation. After completing an MS/BS program at Yale University, he then earned his MD and PhD at Harvard University, completing his PhD in the laboratory of Dr. Laurie Glimcher (a Pershing Square Sohn Cancer Prize Advisory Board Member Emeritus). Currently, he is in the department of Pathology and Laboratory Medicine at Weill Cornell Medicine. In addition to research, he serves as a pathologist at New York Presbyterian/Weill Cornell Medical Center.

Dr. Greenblatt is one of the leading researchers studying the relationship between bone biology and diseases like cancer and Alzheimer's. His innovative research has shed light on critical processes involved in skeletal health and disease with far-reaching potential implications.

Dr. Greenblatt is a special case for PSF, as he is the first person to receive both the Pershing Square Sohn Cancer Prize and the MIND Prize, which supports and empowers early-to-mid-career investigators to rethink conventional paradigms around neurodegenerative diseases. His focus on establishing the identity of the stem cells forming bone has allowed him to investigate how these new stem cells drive not only skeletal diseases, but also a wider set of diseases throughout the body.

With the support of a 2019 Pershing Square Sohn Cancer Prize, his lab identified a new stem cell forming the vertebrae that contributes to the high rates of breast cancer metastasis to the spine over other skeletal sites. According to Dr. Greenblatt’s study in Nature, the vertebral bones of the spine come from a specific stem cell that secretes a protein, MFGE8, which can drive tumor cells to the spine (Sun et al., 2023). This PSF-funded publication has received coverage by The Washington Post and 109 other news articles—placing it in the top 5% of papers published in Nature. This finding opens a new therapeutic avenue to develop antibodies that target this vertebral stem cell derived factor to prevent the vertebral metastases that can occur after surgical removal of a breast cancer primary tumor. As cancer metastasis is the primary cause of morbidity and mortality and responsible for about 90% of cancer deaths, this could be a groundbreaking opportunity to save lives.

With his 2023 MIND Prize project, the Greenblatt lab will investigate whether low bone mass accelerates Alzheimer's Disease progression and neurocognitive decline, exactly the type of out-of-the-box, big idea that PSF and MIND strive to support. Overall, he anticipates that this project will not only establish a new and surprising link between the skeleton and neurodegeneration, but moreover provide insights into how optimizing bone health may offer a new avenue to slow Alzheimer's Disease progression. While only a year underway at the time of writing, his lab has already made several major discoveries supporting the concept that specific regions of the skeleton house fundamentally different and new cell types that are likely to strongly impact the progression of neurodegenerative diseases such as Alzheimer’s.

PSF is a core supporter of the Greenblatt lab, which is one of the few in the nation that is working to identify new cell types in bone and determine how this often-overlooked organ plays a broad and sometimes unexpected role in a wide range of human diseases manifesting throughout the body.

Dr. Matthew Greenblatt has made several significant contributions to the field of bone biology and pathology through his research. His work primarily focuses on understanding the cellular and molecular mechanisms that regulate bone remodeling, which is crucial for addressing various bone diseases and conditions, including osteoporosis and bone metastasis in cancer. Highlights of his work include the discovery of the stem cell on the outer surface of bones, two new stem cells forming the skull, and stem cells in the vertebrae. His studies have been in Nature, Nature Medicine, Nature Communications, and Science. Dr. Greenblatt is an expert in all things bone and, with the continued support from PSF, has dedicated his career thus far to exploring how bone affects the body holistically and contributes to disease progression, from cancer to neurodegeneration.

• Pakula, H., Omar, M., Carelli, R., Pederzoli, F., Fanelli, G. N., Pannellini, T., Socciarelli, F., Van Emmenis, L., Rodrigues, S., Fidalgo-Ribeiro, C., Nuzzo, P. V., Brady, N. J., Dinalankara, W., Jere, M., Valencia, I., Saladino, C., Stone, J., Unkenholz, C., Garner, R., Alexanderani, M. K., Khani, F., de Almeida, F. N., Abate-Shen, C., Greenblatt, M. B., Rickman, D. S., Barbieri, C. E., Robinson, B. D., Marchionni, L., & Loda, M. (2024). Distinct mesenchymal cell states mediate prostate cancer progression. Nature Communications, 15(1), 363. https://doi.org/10.1038/s41467-023-44210-1

• Chen, R., Dong, H., Raval, D., Maridas, D., Baroi, S., Chen, K., Hu, D., Berry, S. R., Baron, R., Greenblatt, M. B., & Gori, F. (2023). Sfrp4 is required to maintain Ctsk-lineage periosteal stem cell niche function. Proceedings of the National Academy of Sciences of the United States of America, 120(46), e2312677120. https://doi.org/10.1073/pnas.2312677120

• Tylawsky, D. E., Kiguchi, H., Vaynshteyn, J., Gerwin, J., Shah, J., Islam, T., Boyer, J. A., Boué, D. R., Snuderl, M., Greenblatt, M. B., Shamay, Y., Raju, G. P., & Heller, D. A. (2023). P-selectin-targeted nanocarriers induce active crossing of the blood-brain barrier via caveolin-1-dependent transcytosis. *Nature Materials, 22*(3), 391-399. https://doi.org/10.1038/s41563-023-01481-9

• Bok, S., Yallowitz, A. R., Sun, J., McCormick, J., Cung, M., Hu, L., Lalani, S., Li, Z., Sosa, B. R., Baumgartner, T., Byrne, P., Zhang, T., Morse, K. W., Mohamed, F. F., Ge, C., Franceschi, R. T., Cowling, R. T., Greenberg, B. H., Pisapia, D. J., Imahiyerobo, T. A., Lakhani, S., Ross, M. E., Hoffman, C. E., Debnath, S., & Greenblatt, M. B. (2023). A multi-stem cell basis for craniosynostosis and calvarial mineralization. Nature, 621(7980), 804-812. https://doi.org/10.1038/s41586-023-06526-2

• Sun, J., Hu, L., Bok, S., Yallowitz, A. R., Cung, M., McCormick, J., Zheng, L. J., Debnath, S., Niu, Y., Tan, A. Y., Lalani, S., Morse, K. W., Shinn, D., Pajak, A., Hammad, M., Suhardi, V. J., Li, Z., Li, N., Wang, L., Zou, W., Mittal, V., Bostrom, M. P. G., Xu, R., Iyer, S., & Greenblatt, M. B. (2023). A vertebral skeletal stem cell lineage driving metastasis. Nature, 621(7979), 602-609. https://doi.org/10.1038/s41586-023-06519-1

• Bok, S., & Greenblatt, M. B. (2022). Shaping the sinuses: A novel Krt14+Ctsk+ cell lineage driving regenerative bone formation. Cell Research, 32(9), 791-792. https://doi.org/10.1038/s41422-022-00694-y

• Sun, J., Shin, D. Y., Eiseman, M., Yallowitz, A. R., Li, N., Lalani, S., Li, Z., Cung, M., Bok, S., Debnath, S., Marquez, S. J., White, T. E., Khan, A. G., Lorenz, I. C., Shim, J. H., Lee, F. S., Xu, R., & Greenblatt, M. B. (2021). SLITRK5 is a negative regulator of hedgehog signaling in osteoblasts. Nature Communications, 12(1), 4611. https://doi.org/10.1038/s41467-021-24819-w

• Bok, S., Shin, D. Y., Yallowitz, A. R., Eiseman, M., Cung, M., Xu, R., Li, N., Sun, J., Williams, A. L., Scott, J. E., Su, B., Shim, J. H., & Greenblatt, M. B. (2020). MEKK2 mediates aberrant ERK activation in neurofibromatosis type I. Nature Communications, 11 (1), 5704. https://doi.org/10.1038/s41467-020-19555-6

• Kim, J. M., Yang, Y. S., Park, K. H., Ge, X., Xu, R., Li, N., Song, M., Chun, H., Bok, S., Charles, J. F., Filhol-Cochet, O., Boldyreff, B., Dinter, T., Yu, P. B., Kon, N., Gu, W., Takarada, T., Greenblatt, M. B., & Shim, J. H. (2020). A RUNX2 stabilization pathway mediates physiologic and pathologic bone formation. Nature Communications, 11(1), 2289. https://doi.org/10.1038/s41467-020-16038-6