Yonghao Yu, PhD

  • Recruited to: The University of Texas Southwestern Medical Center
  • Recruited from: Harvard Medical School
  • Award: First-Time, Tenure-Track Faculty Member

Dr. Yonghao Yu joins the Department of Biochemistry at the University of Texas Southwestern Medical Center. He is an analytical biochemist who uses quantitative mass spectrometry to uncover how signal transduction networks wire in cancer cells.

Dr. Yu became fascinated by molecules during his childhood, leading him to pursue his Bachelor’s degree in Chemistry at Fudan University. There he was named a “Chun-Tsung Scholar” by the Hui-Chun Chin and Tsung-Dao Lee Endowment, and performed undergraduate research in design and characterization of nanoporous materials.

Never having left the city of Shanghai where he was born and raised, his first long-distance trip in fact took him across the Pacific Ocean to the San Francisco Bay area in 2001, to attend graduate school at the University of California, Berkeley. There he joined the lab of Dr. Julie Leary in the Department of Chemistry and began his career as an analytical biochemist. He developed FT-ICR mass spectrometric techniques to characterize protein-protein, protein-carbohydrate and protein-drug interactions. In particular, he designed and developed the first general method for pinpointing a post-translational modification, tyrosine sulfation. Using this method, he uncovered the pattern of tyrosine sulfation on a series of human chemokine receptors, which led to a critical understanding of the role this important modification plays in regulating protein-protein interaction.

To pursue postdoctoral training, he joined Drs. Steven Gygi and John Blenis labs in the Department of Cell Biology at Harvard Medical School where he continued to be involved in the development of mass spectrometry technologies and their application in the field of cancer signal transduction. In the first project, he developed a multiplexed, mass-spectrometry-based in vitro kinase assay which allows concurrent measurement of hundreds of site-specific peptide phosphorylation rates, reporting a diagnostic fingerprint for activated kinase pathways in cancer cells. His second project is focused on the mTOR pathway. The evolutionarily conserved kinase, mTOR, plays a critical role in regulating cell growth, proliferation, migration and survival. Numerous upstream genetic alterations converge on mTOR, leading to its hyperactivation in a broad spectrum of human cancers. However, the clinical evaluation of the mTORC1 inhibitor, rapamycin, in treating cancers has yielded mostly disappointing results, which is due in part to rapidly developed resistance to the drug. To improve on rapamycin therapies, understanding how resistance occurs, identifying new therapeutic targets for future drug development, and revealing new biomarkers to improve on current assays used to monitor disease progression, Dr. Yonghao Yu took a global phospho-proteomic approach towards defining the signaling landscape downstream of both mTORC1 and mTORC2. He uncovered a new mechanism for rapamycin resistance that provides opportunities for improving therapy, identified a possible tumor suppressor, and provided the entire research community with many new mTOR targets that will seed the discovery of new mechanisms that contribute to mTOR-mediated tumorigenesis, and thus new therapeutic strategies.

At UT Southwestern, Dr. Yu will continue to employ cutting-edge mass spectrometric technologies to characterize cancer signal transduction networks and to elucidate the fundamental mechanism of tumorigenesis.