Anita C. Bellail, PhD, Lab

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 programed 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:

• 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

Dr. Bellail grew up along the coast of Normandy in France. She received her BA in Cell Biology, MSc in Biochemistry and PhD in neuroscience from the University of Caen in France. Under the support of the French Association for Cancer Research scholarship, she came to the US in 2002 and started her postdoctoral training at the Winship Cancer Institute of Emory University, Atlanta. In 2013, Dr. Bellail became Assistant Professor of Neurology and Neurological Surgery of the Montreal Neurological Institute at McGill University in Canada. In 2014, she moved back to the US and worked as a principal investigator at the Henry Ford Health System Research Institute, Michigan. In January 2018, Dr. Bellail joined the Indiana University School of Medicine as Assistant Professor, tenure-tracked, of Pathology and Laboratory Medicine.

Building on her research experience in protein ubiquitination and degradation, Dr. Bellail started her translational research in targeted protein degradation drug discovery. Her team has developed disease cell-based drug screening and identified molecular glue degraders of oncoproteins and aging proteins. She published her work in high impact journals and filled several patents of the compounds as therapeutics. She co-founded two start-up companies and serves as chief executive officer (CEO) of one and chief scientific offer (CSO) of another company, leading the development and commercialization of molecular glue degraders as the first-in-class anticancer and antiaging drugs.

Anita Bellail, PhD, Assistant Professor

Chunhai Charlie Hao, MD, PhD, Bicentennial Professor, Neuropathologist

Bin Liu, PhD, Sr Research Professor, Medicinal chemistry, Former Sr Research Advisor

Sunghan Jung, PhD in South Korea, Assist Research Professor

Raktim Roy, PhD under the Nobel-Laureate Dr Steitz at Yale, Assist Research Professor

Nancy Jaiswal, PhD in Biotechnology, Assist Research Professor

Xu Wang, PhD, Medicinal chemistry, pharmaceutical experience, drug design

Min Zhou, PhD, Pharmaceutical biology, Johannes Gutenberg-Universitat, Mainz, Germany

Han Nguyen, PhD, chemistry, and biomedical engineering, Purdue University

1. Bellail AC, Olson J, Yang X, Chen Z, Hao C. A20 ubiquitin ligase-mediated polyubiquitination of RIP1 inhibits caspase-8 cleavage and TRAIL-induced apoptosis in glioblastoma. Cancer Discov 2012 Feb; 2(2):140-155. Epub 2012 Jan 24. PMID: 22585859. PMCID: PMC3354650.

2. Bellail AC, Olson JJ, Hao C. SUMO1 modification stabilizes CDK6 protein and drives the cell cycle and glioblastoma progression. Nat Commun 2014 June 23; 5:4234. PMID: 24953629. PMCID: PMC4090607.

3. Bellail AC, Jin HR, Lo HY, Jung SH, Hamdouchi C, Kim D, Higgins RK, Blanck M, le Sage C, Cross BCS, Li J, Mosley AL, Wijeratne AB, Jiang W, Ghosh M, Zhao YQ, Hauck PM, Shekhar A, Hao C. Ubiquitination and degradation of SUMO1 by small-molecule degraders extends survival of mice with patient-derived tumors. Sci Transl Med. 2021 Oct 13;13(615):eabh1486. doi: 10.1126/scitranslmed.abh1486. Epub 2021 Oct 13.PMID: 34644148.

4. Jung S, Jaiswal N, Rai RK, Takagi Y, Lo HY, Gao C, Zeng L, Wang X, Wohlford RK, Higgins RK, Bellail AC, Hao C. Small-molecule degraders reduce Aβ production through CAPRIN1-mediated lysosomal degradation of APP in Alzheimer’s iPSC-derived neurons. bioRxiv. 2023; Dec 29:2023.12.29.573648. doi: https://doi.org/10.1101/2023.12.29.573648.