Research in the Hao Lab

Chunhai Hao, MD, PhD, and Anita Bellail, PhD, have been collaborating and building up a research team together. The focus of the team is on protein ubiquitination and degradation in human diseases. The team has developed a novel platform of targeted protein degradation for discovery of molecular glue degraders that can destroy disease-causing proteins. The team has reported the first molecular glue degraders of SUMO1 and revealed the targeted E3 ligase complex for SUMO1 degradation in cancer cells. Recently, the team has identified the molecular glue degraders of APP that degrade APP and reduce Aβ amyloid accumulation in Alzheimer's brains. Drs. Hao and Bellail co-founded the start-up biotech HB Therapeutics, Inc., for commercialization of the molecular glue degraders of oncoproteins as the first-in-class anticancer drugs. Recently, they co-founded the Degrome Therapeutics, Inc., for development and commercialization of APP degraders as the first-in-class drugs for Alzheimer’s disease. The projects are currently funded by the following NIH and foundation grants:

• NIH/NIA R41 AG090241-01, 2024.08.27 – 2026.08.26, PI: Hao C
  Development of Small-Molecule Degraders of APP as the first-in-class drugs for Alzheimer's 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, R01 CA288899, 2022.07.01 – 2027.06.30, PI: Bellail A, co-I: Hao C
  Targeting SUMO1 degradation for advanced colon cancer therapy

• NIH/NCI, 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

• The Ben and Catherine Ivy Foundation, 2023/07/01 – 06/30/2025, PI: Hao C
  Structural mechanism and glioblastoma therapy of SUMO1 small molecule degraders

Anita Bellail, PhD, Assistant Professor (tenure-tracked)

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

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.

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.

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.

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.