Memorial Sloan Kettering Cancer Center
I believe that a detailed understanding of basic biological signaling pathways, and especially the networks that control immune responses, will lead to transformational new therapies for cancer. My lab uses a variety of chemical biology tools and approaches, including selective enzyme inhibitors, reactive chemical probes, and mass spectrometry-based proteomics, coupled with biochemistry and genetics to characterize these important pathways. We anticipate that this work will lead to new therapeutic targets and lead compounds.
Dr. Bachovchin received an A. B. in Chemistry from Harvard in 2005. He then obtained a Ph.D. in Chemical Biology from The Scripps Research Institute in 2011 under the supervision of Ben Cravatt. After completing post-doctoral training with Todd Golub at the Broad Institute of MIT and Harvard in 2015, he started his independent laboratory in the Chemical Biology Program at Memorial Sloan Kettering Cancer Center. His lab studies the roles that proteases play in cancer and immune system signaling. His recent work has identified a checkpoint that restrains the innate immune system and is a potential target for new immuno-oncology agents. Dr. Bachovchin’s recent honors and awards include a Josie Robertson Fellowship, a Stand Up To Cancer Innovative Research Grant, a Sloan Research Fellowship in Chemistry, and a Pew-Stewart Scholarship for Cancer Research.
A Chemoproteomic Protease Profiling Platform for Understanding Immune System Signaling
Proteases are enzymes that act as molecular scissors to cleave other proteins. Proteases play key roles in a wide range of important biological responses, including in the activation of immune responses. For example, we recently discovered that two proteases, DPP8 and DPP9, act as a checkpoint to restrain the activation of the innate immune system. Excitingly, drugs that block the activity of DPP8/9 activate anti-cancer immune responses and have promise to become new cancer immunotherapy agents.
“The generous support from the Pershing Square Sohn Prize will enable my group to develop and apply an innovative approach to identify protease substrates. This technology will allow us to understand several important, yet enigmatic biological pathways in cancer and immune signaling, which can then be effectively targeted by novel therapeutics.”
However, how DPP8/9 inhibition activates the immune system has not been fully established. Most notably, the key protein substrates of DPP8/9 have not been identified, largely due to technological limitations. This gap in knowledge hampers our ability to harness this biological pathway for therapeutic benefit. Here, we will introduce an innovative technology that will enable the rapid identification of protease substrates. We will use this technology to identify and characterize the substrates of DPP8/9, which we anticipate will enable the development of a new immunooncology agent.
“There are at least two types of innovation in the biomedical sciences. One type of innovation comes from re-considering biological concepts in new ways, which can lead to new hypotheses and transformative discoveries. The other type of innovation comes from the creation of new technologies that enable us to ask questions that were previously impossible to consider.”