MechE PhD Prospectus Defense: Nazanin Nafisi

TITLE: CROSS-SPECIES MECHANICS-INFORMED FRAMEWORK OF BONE FRACTURE HEALING USING MULTI-OMICS DATA

ABSTRACT: Bone fracture healing is a regenerative process in which molecular signaling and tissue differentiation are mechanically regulated to structurally adapt to restore function. Although high-dimensional omics approaches provide detailed insight into early biological states, they are rarely integrated with quantitative measures of mechanical competence and clinical recovery. This gap limits mechanistic understanding and translational application. The objective of this work is to develop a cross-species, mechanics-informed multi-omics framework that links early molecular dynamics to radiographic progression, functional recovery, and structural integrity during fracture healing. We hypothesize that time resolved molecular signatures encode conserved molecular–mechanical relationships that confer biomechanical competence to skeletal tissues during healing, and that these relationships can be identified through cross-species comparisons. In rodent fracture models, we will integrate transcriptomic and proteomic data with longitudinal functional and radiographic measures to determine whether early molecular modules predict spatial tissue formation and recovery trajectories (Aim 1). In human fracture patients, we will test whether early plasma proteomic signatures improve prediction of radiographic and clinical outcomes beyond imaging alone (Aim 2). Finally, we will identify conserved molecular–mechanical regulators of successful healing across species (Aim 3). Collectively, this work will establish an omics-informed mechanobiological framework for predicting fracture healing trajectories, improve translational alignment between animal models and patients, and enable early identification of individuals at risk for delayed healing or non-union.

COMMITTEE: ADVISOR/CHAIR Professor Ara Nazarian, ME; Professor Lou Gerstenfeld, Orthopedic Surgery; Professor Elise Morgan, ME/MSE/BME; Professor Michael Albro, ME/MSE/BME