Dr. Bellail’s research is centered on the posttranslational modifications of ubiquitin (UB) and small ubiquitin-like modifier-1 (SUMO1). She started her research on UB modification pathways in cancer and revealed that UB E3 ligase A20 mediates the K63-linked poly-ubiquitination of RIP1 that inhibits caspase-8-mediated cancer cell programmed death in the cancer resistance to apoptotic drugs. This work was published in the high impact journal Cancer Discovery. Subsequently, she identified the small ubiquitin-like modifier-1 (SUMO1) as an oncoprotein that drives cancer cell cycle progression through its modification and stabilization of cyclin dependent kinase 6 (CKD6), which was published in Nature Communications.
Since she joined IU, she has been teaming up with Chunhai Hao, MD, PhD, a physician-scientist, in targeted protein degradation (TPD) drug discovery and development. The team has developed a TPD platform of cell-based drug screening and identified the first compounds that degrade SUMO1 protein in cancer cells. Using the advanced technologies including CRISPR-Cas9 genome-wide screening, the team demonstrated that the compounds act as molecular glues that binding CAPRIN1 and FBXO42, resulting in FBXO42-medicated recruitment of SUMO1 to the CUL1-E3 ligase for SUMO1 ubiquitination and degradation in cancer cells. This work was published in Science Translational Medicine. Drs. Hao and Bellail co-founded the HB Therapeutics, inc. for development of molecular glue degraders of oncoproteins as first-in-class anticancer drugs. Most recently, the team discovered molecular glue degraders of amyloid precursor protein (APP) and demonstrated that the degraders induce APP degradation through the endolysosomal pathway in human neurons differentiated from AD patient derived induced pluripotent stem cells (iPSCs). The treatment of APP degrader compounds reduces APP and Aβ amyloids in the brains of Alzheimer’s mouse models. Drs. Bellail and Hao co-founded Degrome Therapeutics, Inc., for development and commercialization of APP degraders as the first-in-class drugs for Alzheimer’s disease. Dr. Bellail has led the success of the team application for NIH/NCI/NIA Small Business Innovation Research (SBIR) and Small Business Technology Transfer Research (STTR) as well as R01 grants. The key current grants include:
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NIH/NIA STTR Phase I R41 AG090241-01, 2024.08.27 – 2026.08.26, PI: Hao C, co-I: Bellail
Development of Small-Molecule Degraders of APP as the first-in-class drugs for Alzheimer's therapy. -
NIH/NCI, R01 CA288899, 2022.07.01 – 2027.06.30, PI: Bellail A, co-I: Hao C
Targeting SUMO1 degradation for advanced colon cancer therapy -
NIH/NINDS, R01 NS126358-01, 2022.03.01 – 2027.02.28, PI: Hao C
Development of BBB-permeable SUMO1 small molecule degraders for glioblastoma therapy. -
NIH/NCI, SBITR Phase II, R44 CA265547, 2022.05.01 – 2025.04.30 (NCE) MPIs: Bellail A, Lo H-Y, Hao C
Development of SUMO1 small molecule degraders as the first-in-class anticancer drugs for metastatic colorectal cancer
