“Open-Surfaceomics” for Identifying Novel Surface PTMs as Immunotherapy Targets in AML

The main problem in treating Acute Myeloid Leukemia (AML), a severe form of blood cancer, is the lack of distinguishable markers on AML cells that can be used to kill the cancer without harming healthy cells. Most AML cell markers are also found on normal cells, making it difficult to make treatments that kill only cancer cells. My project aims to address this issue by identifying unique features on the surface of AML cells, which we can use to develop safer and more precise treatments. I believe there are specific modifications or small chemical changes called "post-translational modifications" (PTMs) appear on certain proteins on the surface of cancer cells but not on normal cells. These modifications act like "flags" that could allow us to distinguish AML cells from healthy cells. But these flags need advanced technology that I am trying to make. My research focuses on finding and targeting these unique modifications on AML cells, specifically looking for a modification called "lysine trimethylation" (or Kme3) that I identified on AML cells but rarely on healthy cells. By targeting these distinct PTMs, I hope to design treatments that specifically seek out and destroy AML cells without affecting healthy ones. In my preliminary research, I developed an approach called "Open Surfaceomics" to study these modifications on AML cells in depth. So far, using this approach, I’ve discovered hundreds of potential PTM "flags" on AML cells that could serve as future therapy targets. I confirmed this by testing a large set of AML samples, finding high levels of Kme3 modifications on important proteins like CD70, CD44, and FLT3, which might be good targets for AML-specific therapies. This project has three main goals. First, I aim to use advanced techniques to verify these PTMs on AML cell surfaces more precisely. Then, I plan to study the biology behind these PTMs to understand why they appear on AML cells. Finally, my team will use protein engineering to develop antibodies that recognize these specific PTMs, with the hope that these antibodies could form the basis of future therapies. If successful, this research could help create "personalized" treatments for AML that target only cancer cells, sparing healthy cells. Although these therapies are still in early stages, they hold the potential to significantly improve the safety and effectiveness of AML treatment, leading to better outcomes for patients with fewer side effects.