Laboratory of Skeletal Stem Cells

Principal Investigator: 
Matthew B. Greenblatt, M.D., Ph.D.

Approximately half of all women and a fifth of all men will experience a skeletal fracture due to osteoporosis or other diseases causing low bone mass. These fractures kill as many women each year as breast cancer, as fractures often lead to immobility that in turn leads a spiral of progressive deconditioning that can ultimately prove fatal. Improving clinical outcomes in this area will ultimately require finding new therapeutic agents that promote the generation or activity of osteoblasts, the cells that build bone. Ultimately, all bone-forming osteoblasts come from skeletal stem cells, an adult stem cell type that has only recently begun to be studied. A key focus of our work has been the idea that there is not a single skeletal stem cell, but many versions of these cells, each residing in different regions of the skeleton and having distinct contributions to both the normal formation of the skeleton and to the development of skeletal diseases. Our work in this area started with the identification of a new stem cell on the outer surface of bone (Debnath et al., Nature 2018) and is now continuing to identify new stem cells in other regions of the skeleton, including the spine and the skull.

We are also investigating the environmental factors and signals that both support these stem cells and drive their production of bone-forming osteoblasts. In our prior work, we have identified that osteoblasts secrete factors known as SLITs that promote the formation of special blood vessels that in turn tailor the environment in bone to favor new bone formation (Xu et al., Nature Medicine 2018). Accordingly, treatment with SLITs can promote new skeletal blood vessel formation and also reverse bone loss in mouse models of osteoporosis or promote healing in models of fracture repair. In other studies, we have identified a new therapeutic target for the treatment of neurofibromatosis type 1, a disorder whose manifestations include skeletal fragility and impaired fracture healing (Bok et al., Nature Communications 2020). Lastly, we have also identified a new receptor on osteoblasts that regulates responses to a family of proteins, termed the hedgehog family, that provide environmental signals controlling bone formation (Sun et al., Nature Communications 2021). Currently, we are both working to explore how these discoveries may be relevant for the treatment of skeletal disorders and also to identify new therapeutic approaches to increase bone mass and prevent fractures, both in osteoporosis and also in rare genetic diseases of bone.

Active Projects

Currently, an area of focus in the lab is understanding how alterations in the signaling of mitogen activated protein kinases contribute to the development of both osteoporosis and rare skeletal disorders, with a particular emphasis on discovering approaches to target these pathways for therapeutic benefit in humans.

Grants

PI: Matthew Greenblatt, M.D., Ph.D.
Novartis Institutes for BioMedical Research

PI: Matthew Greenblatt, M.D., Ph.D.
Weill Cornell Medical College

PI: Matthew Greenblatt, M.D., Ph.D.
National Institute of Arthritis & Musculoskeletal & Skin Diseases

PI Subaward: Matthew Greenblatt, M.D., Ph.D.
National Institute of Dental & Craniofacial Research

PI Subaward: Matthew Greenblatt, M.D., Ph.D.
National Cancer Institute

PI: Matthew Greenblatt, M.D., Ph.D.
The Pershing Square Sohn Cancer Research Alliance

Co-Investigator: Matthew Greenblatt, M.D., Ph.D.
National Institute of Child Health & Human Development

PI: Matthew Greenblatt, M.D., Ph.D.
Burroughs Wellcome Fund Career Award for Medical Scientists

PI: Matthew Greenblatt, MD PhD
United States Department of Defense (DOD)- Incoming Subaward

Lab Team

Laboratory of Skeletal Stem Cells Team

Additional Key Academic Personnel

Seoyeon Bok
Post Doc
seb4003@med.cornell.edu
Shawon Debnath
Research Associate
shd2030@med.cornell.edu
Yuzhe Niu
Post Doc
yun4003@med.cornell.edu
Jun Sun
Post Doc
jus4001@med.cornell.edu
Alisha Yallowitz
Research Associate
aly2009@med.cornell.edu

Contact Information

Matthew B. Greenblatt, M.D., Ph.D.
Associate Professor of Pathology and Laboratory Medicine
Weill Cornell Medical College

Office: 212-746-1602
Lab: 212-746-1095

1300 York Ave
LC-929a
New York, NY 10065

Pathology & Laboratory Medicine 1300 York Avenue New York, NY 10065 Phone: (212) 746-6464
Surgical Pathology: (212) 746-2700