Lachlan James Smith

Lachlan James Smith is a Professor of Orthopaedic Surgery at the Perelman School of Medicine, University of Pennsylvania, and Co-Director of the Histology Core at the Penn Center for Musculoskeletal Disorders. His research focuses on the pathophysiology and treatment of degenerative and developmental spine/joint disorders using multidisciplinary approaches spanning molecular biology, bioengineering, and clinical translational studies.

• PhD in Pathology (University of Adelaide, 2008)
• Postdoctoral Fellow & Research Associate at University of Pennsylvania (2008-2013)

Research spans molecular mechanisms of skeletal disease in mucopolysaccharidoses (MPS), with emphasis on glycosaminoglycan accumulation, vascularization defects, and Wnt/β-catenin signaling. His lab develops in utero stem cell therapies and injectable hydrogel systems for disc regeneration. Collaborations involve biologists, clinicians, and veterinarians using canine and goat models.

Recent publications highlight mRNA delivery systems (2025), single-cell transcriptomics (2024), and biomechanical markers for scoliosis (2024). The lab has secured NIH R01 grants and industry partnerships for developing regenerative therapeutics.

• 2021: R01 grant - Neutralizing disc microenvironment
• 2019: Lisa Dean Moseley Foundation Grant
• 2017: R01 grant - MPS bone disease pathogenesis
• 2016: Penn Orphan Diseases Center Grant
• 2015: ISSLS Prize for disc nutrition research

Lab personnel include graduate students and postdocs working on CRISPRa gene regulation, scaffold development, and non-invasive imaging techniques. Current projects evaluate trans-endplate diffusion and multiplex gene targeting for enhancing engineered disc properties.