jllahti at stanford.edu

Broke her finger coaching basketball at the Special Olympics.

Education

MS in Bioengineering, Stanford University, 2006
BS in Bioengineering, University of Utah, 2004

Research

ErbB receptors are displayed on the exterior surface of many breast tumor cells and transmit molecular signals from the extracellular environment to the inside of the cell. In this way, they mediate normal cell processes and functions, but in breast tumors can trigger aberrant cell growth. This growth regulatory role makes the ErbB receptors attractive targets for therapeutic intervention. In particular, the epidermal growth factor receptor (EGFR), an ErbB receptor, has been shown to be present in up to 90% of breast cancer tumors and metastases. The presence of EGFR on the surface of breast tumor cells has been shown to correlate with tumor aggressiveness and poor clinical prognosis. To activate EGFR, specific ligands attach to the extracellular domain of the receptor.  Then, the activated EGFR associates with another activated EGFR or ErbB receptor family member, forming a receptor complex. The intracellular regions of these receptors are then responsible for communicating biological signals to the rest of the cell.

Current antibody-based therapies targeting the extracellular domain of EGFR are limited by high production cost, poor tumor penetration, and unwanted side effects.  The goal of this proposal is to develop novel breast tumor-targeting agents that will: (1) bind cell surface EGFR with high affinity, (2) block natural ligand binding, and (3) prevent homo- or heterodimerization of ErbB receptors, consequently inhibiting tumor cell signaling and progression. These novel EGFR antagonists will be created by applying interdisciplinary molecular engineering techniques. Rational design will be used to incorporate portions of natural ligands into alternate polypeptides that possess native receptor binding conformations but cripple receptor-mediated signaling critical for tumor growth. These polypeptides will then be engineered for high EGFR binding affinity through directed evolution using yeast surface display.