St. Jude Children’s Research Hospital
Two summers of cancer research in Memphis: structural biology in the Kalodimos Lab, then computational biology in the Yu Lab.
Memphis, 2023 and 2024Illuminating the Molecular Dance
Characterization of the ALK receptor and AUG-α ligand complex
ALK is a receptor tyrosine kinase that drives several cancers, including anaplastic large cell lymphoma, neuroblastoma, and 3 to 7% of non-small cell lung cancers. Its ligand, AUG-α, activates it, but the field had seen two different answers for how the pair assembles: two ligands to one receptor, or two to two.
My project built a purification protocol for a “full-length” ALK receptor (residues 673 to 1407) and for AUG-α, bound the two into a complex, stabilized it with gradient fixation (GraFix), and checked it with negative-stain electron microscopy. The complex came out uniform and consistent with a 2:2 assembly, clean enough for high-resolution cryo-EM. Along the way, Kaplan-Meier analysis showed that higher ALK expression tracks with worse survival across eight tumor types.
Investigating the Role of LOXL2 in Intrahepatic Cholangiocarcinoma
Expression profiling, gene network analysis, and survival outcomes
Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver cancer. Fewer than 10% of patients survive five years, and 60 to 70% relapse after surgery. Earlier spatial and single-cell work in the lab had flagged LOXL2, an enzyme that crosslinks collagen in the tissue around a tumor, as a possible master regulator of how iCCA spreads.
My project asked whether LOXL2 matters clinically. In two datasets, TCGA and Kang, it is significantly higher in tumors than in normal liver, and high expression tracked with worse survival in all six patient cohorts I tested, significantly in two. I then re-analyzed a single-cell dataset (GSE138709, about 30,000 cells after quality control) with scMINER, which I was also benchmarking. LOXL2 is expressed mostly in fibroblasts but active across the tumor's cell types, and its top targets in fibroblasts include SLIT3, THY1, ADAMTS12, COL5A2, and COL6A3.
Thanks to Dr. Charalampos Kalodimos and Andrey Reshetnyak in Structural Biology, and to Dr. Yu and Dr. Pan in Computational Biology, for having me in their labs.