Education

2011 Ph. D., School of Biological Sciences, Nanyang Technological University, Singapore

2005 B.S., Biomedical Sciences, National University of Singapore, Singapore

Professional Experience

2015- Assistant Investigator, National Institute of Biological Sciences, Beijing, China

2010-2015 Postdoctoral Fellow, Johns Hopkins University School of Medicine, Maryland, USA

2006-2007 Project Officer, School of Biological Sciences, Nanyang Technological University, Singapore

2005-2006 Research Assistant, Department of Biological Sciences, National University of Singapore, Singapore

Research Description

The main interest of our group is to elucidate the function and mechanism of small molecules that are emerging messengers. Endogenous small molecules such as cyclic nucleotides and inositol triphosphates (IP3) are well-established 2nd messengers transducing extracellular stimulus into intracellular activities. IP3 is step-wise phosphorylated by a family of inositol phosphate kinases generating higher inositol polyphosphates (IP4-8) whose physiology remains poorly understood. In particular, inositol pyrophosphates (IP7/8) containing energetic pyrophosphate bond(s) are enigmatic inositol derivatives dynamically generated from inositol hexakisphosphate (IP6) by IP6 kinases (IP6Ks) and IP7 kinases (PPIP5Ks). We recently found that IP7 allosterically modulates CK2 to influence DNA damage response and cell death, processes linked to tumor initiation. Meanwhile, IP7 is essential for tumor metastasis. We also demonstrated that IP6K1 is a key switch dictating ultra-violet light-dependent activation of Cullin 4-based E3 ubiquitin ligases, the physiological relevance of which and mechanisms of action of IP7 remain unclear. By studying the regulation of IP6Ks and enzymes leading to IP6 production in cell- and animal-based models, we aim to uncover the (patho)physiology (e.g. cell migration and cancer metastasis) and signal transduction pathways mediated by inositol pyrophosphates. On top of this, we employ chemical and biochemical approaches to identify effector modules and their mode of interactions, with the goal to unravel underlying principles of inositol pyrophosphate signaling. Given the key roles of IP6K/IP7 in tumor progression and other diseases processes, the mechanistic and functional insights gained from this investigation will hopefully provide new therapeutic targets.

Publications

1. Rao F. #, Xu, J. #, Fu, C., Cha, J., Xu, R., Gadalla, MM., Wu, M., Fiedler, D., Barrow, JC., Snyder, SH. Inositol pyrophosphates promote cancer growth and metastasis by antagonizing the tumor suppressor LKB1. Proc. Natl. Acad. Sci. 2015 112, 1773-8 (#= Co-first author).
2. Rao F. #, Xu, J. #, Kahn, AB., Cha, J., Xu, R. Tyagi, R., Dang, Y., Chakraborty, A., Snyder, SH. Inositol hexakisphosphate kinase-1 mediates assembly/ disassembly of the CRL4-Signalosome complex to regulate DNA repair and cell death. Proc. Natl. Acad. Sci. 2014 111, 16005-16010. (#= Co-first author).
3. Rao F., Cha, J., Xu, J., Xu, R., Vandiver, MS., Tokhunt, RT., Wu, M., Fiedler, D., Barrow, J., Snyder, SH. Inositol pyrophosphates mediate the DNA-PK/ATM-p53 cell death pathway by regulating CK2 phosphorylation of Tti1/Tel2. Mol. Cell 2014 54, 119-32.
4. Rao, F., See, RY., Zhang, D., Toh, DC., Liang Z-X. YybT is a signaling protein that contains a cyclic-di-nucleotide phosphodiesterase domain and a GGDEF domain with ATPase activity. J. Biol. Chem. 2010, 285:473-82.
5. Tan E#., Rao F#., Pasunooti S., Pham TH., Soehano I., Turner MS., Liew CW., Lescar J., Pervushin K., Liang Z-X. Solution structure of the PAS domain of a thermophilic YybT homolog reveals a potential ligand-binding site. J. Biol. Chem. 2013, 288:11949-59. (#= Co-first author).
6. Rao, F.*, Qi, Y., Murugan, E., Pasunooti, S., Ji, Q. 2’,3’-cAMP hydrolysis by metal-dependent phosphodiesterases containing DHH, EAL, and HD domains is non-specific: implications for PDE screening. Biochem. Biophys. Res. Commun. 2010, 398:500-505. (*= Corresponding author)
7. Rao, F., Pasunooti, S., Ng, Y., Zhuo, W., Lim, L., Liu, AW., Liang Z-X. Enzymatic synthesis of c-di-GMP using a thermophilic diguanylate cyclase. Anal. Biochem. 2009, 389:138-42.
8. Rao, F., Ji, Q., Soehano, I., Liang, Z-X. Unusual Heme-Binding PAS Domain from YybT Family Proteins. J. Bacteriol. 2011, 193:1543-1551.
9. Rao, F., Qi, Y., Chong, HS., Kotaka, M., Li, B., Lescar, J., Tang, K., Liang, Z-X. The functional role of a conserved loop in EAL domain-based c-di-GMP specific phosphodiesterase. J. Bacteriol. 2009, 191:4722-31
10. Rao, F., Yang, Y., Qi, Y., Liang, Z-X. Catalytic mechanism of C-di-GMP specific phosphodiesterase: a study of the EAL domain containing protein RocR from Psudomonas aeruginosa. J. Bacteriol. 2008, 190:3622-31
11. Rao, F., et al. Hong, Y. Medaka tert produces multiple variants with differential expression during differentiation in vitro and in vivo. Int. J. Biol .Sci. 2011, 7(4):426-439.

Patent
Liang, Z-X., Rao, F. Diguanylate cyclase method of producing the same and its use in the manufacture of cyclic-di-GMP and analogues thereof. 2014, US Patent No: 8,859,237.