Vashishth Laboratory

Vashishth Laboratory Group Photo
Director
Deepak Vashishth

Because bone's ECM and its modifications are determined by events at molecular, cellular, and tissue levels, our research spans these natural length scales in bone. Using approaches from the fields of mechanics, material science, biochemistry and cell biology we create and use experimental model systems to investigate the mechanics and biology of bone fragility associated with aging, osteoporosis and diabetes.

At the molecular level, we have identified the age-related accumulation of advanced glycation end-products (AGEs) in type I collagen of bone and are currently investigating the mechanisms by which it accumulates and modifies the energy dissipation characteristics of bone. In particular, studies are ongoing on naturally aged and Insulin-like Growth Factor-I (IGF-I) deficient and osteocalcin knock-out mice to determine if IGF-I and osteocalcin play a role in controlling the AGEs accumulation in bone.

At the cellular level, we work with adult human mesenchymal stem cells (hMSCs) and osteoclasts to study factors affecting bone quantity and its interaction with bone quality. The acquisition of bone is investigated from a mechanobiology perspective in which the role of mechanics in determining stem cell fate is of particular interest. Osteoclasts or the principal bone resorbing cells are being investigated to ascertain whether the modification of bone quality by mechanical damage or by protein modification enhances bone resorption affecting the amount of bone.

At the tissue level, the effect of AGEs, non-collagenous matrix proteins, mechanical damage and multiaxial cyclic loading on bone fracture are being investigated. Using a combination of fracture mechanics approach, multiphoton confocal imaging, laser microdissection and proteomics we are investigating the biomolecular basis of osteoporotic and diabetic fractures.

Vashishth Laboratory research image one
Post-translation modifications of bone proteins associated with fracture (left) is investigated using atomic force microscope (AFM) based force spectroscopy (middle and right), ultra-high performance liquid chromatography (UPLC) and genetically engineered mice models.
Vashishth Laboratory research images two
Human bone marrow derived adult mesenchymal stem cells showing expression of bone specific protein osteocalcin upon exposure to select mechanical signal (left). Human bone marrow derived osteoclasts used for examining the effects of matrix quality on bone resorption in an in vitro in cell-tissue culture model.
Vashishth Laboratory research image three
Damaged areas of bone are laser micro-dissected (left), extracted (middle; MMI Cell Cut System) and used to identify modifications of bone proteins by mass spectroscopy (right).
Vashishth Laboratory Group hiking on Crane Mountain
Hiking the Crane Mountain, Adirondacks National Park