Haiwei SONG

• 2023 Co-PI of an IAF-PP grant aimed at Strategic Optimization of mRNA vaccines for Preparedness of COVID-19 Variants
• 2023 Co-PI of mRNA manufacturing Project supported by Council Strategic Fund
• 2023 Co-PI of two CRP grants aimed at Identifying functional RNA tertiary structures in dengue virus and Developing RNA vaccines for dengue virus (2022)
• 2021 Co-PI of RNA Vaccines Research project supported by Council Strategic Fund
• 2019 OFIRG grant
• 2016 OFIRG grant

Targeting long noncoding RNAs (lncRNAs) with small molecules for cancer therapy
Long non-coding RNAs (lncRNAs) play key roles in regulating gene expression and are often dysregulated in cancer, contributing to tumor growth, metastasis, and treatment resistance. lncRNAs targeting small molecules offer a unique advantage, as they can selectively bind to lncRNAs, disrupting their structure and function. By inhibiting oncogenic lncRNAs or modulating the activity of tumor-suppressive lncRNAs, these small molecules can effectively impede cancer progression. This approach not only provides a new avenue for therapeutic intervention but also opens up possibilities for overcoming the limitations of traditional protein targeting therapies, such as off-target effects and drug resistance.

Developing circular production technology for vaccines and protein replacement therapy
Circular RNA (circRNA) has emerged as a promising new drug modality, holding significant potential as an alternative to linear mRNA for producing proteins of interest inside cells. While it is poised to reshape the landscape of the mRNA pharmaceutical industry, scalable circRNA manufacturing remains a formidable challenge. This is due to inefficiencies in circularizing longer RNA molecules, substantial occurrences of circRNA damage, and a complex, multi-step process impeding low cost and rapid production. The objectives of this proejcts are: (1) improving the RNA circularizarion efficiency by engineering the group I intron ribozyme; (2) simplifying the circularization process by consolidating plasmid linearization, in vitro transcription (IVT), and RNA circularization into a single step; (3) developing a scalable and cost-effective circRNA purification method for rapid manufacturing.

• Eukaryotic Pif1 helicase unwinds G-quadruplex and dsDNA using a conserved wedge.
  Hong Z, Byrd AK, Gao J, Das P, Tan VQ, Malone EG, Osei B, Marecki JC, Protacio RU, Wahls WP, Raney KD, Song H (2024).
  Nature Commun. 15, 6104.
  
  
• Structural basis for reactivating the mutant TERT promoter by cooperative binding of p52 and ETS1.
  Xu X, Li Y, Bharath SR, Ozturk MB, Bowler MW, Loo BZL, Tergaonkar V, Song H (2018).
  Nature Commun. 9, 3183.
  
  
• Structural basis of suppression of host translation termination by Moloney Murine Leukemia Virus.
  Tang X, Zhu Y, Baker SL, Bowler MW, Chen BJ, Chen C, Hogg  JR, Goff SP, Song H (2016).
  Nature Commun. 7, 12070.

• Structural basis of YAP recognition by TEAD4 in the Hippo pathway. 
  Chen L, Chan SW, Zhang  X, Walsh M, Lim CJ, Hong W  and Song  H（2010）
  Genes & Dev. 24, 290-300.

• Structural basis of Dcp2 recognition and activation by Dcp1.
  She M, Decker CJ, Svergun DI, Round A, Chen N, Muhlrad D, Parker R, Song H. (2008).
  Mol. Cell 29, 337-349.

• RF3 Induces ribosomal conformational changes responsible for the dissociation of class-I release factor.
  Gao, H.,  Zhou, Z., Rawat, U., Huang, C., Bouakaz, L., Wang, C., Cheng, Z., Liu, Y., Zavialov, A., Gursky, R., Sanyal, S., Ehrenberg, M., Frank, J. and Song H.  (2007).
  Cell  129, 929-941.