Feng Cai, Assistant Professor, Research

Research Focus

The dynamic rearrangement of carbon atoms during biotransformation can provide valuable insights into biological system alterations. For example, biotransformation in the TCA cycle involves recurring C-C bond formation, decarboxylation, and backward scrambling. Consequently, a specific atom from a nutritional molecule may end up in almost any position within TCA intermediates. These subtle rearrangements can be tracked using stable isotope labeling. While significant progress has been made in deciphering these puzzles through NMR and LC-MS, there is still much ground to cover. Trained as an organic chemist — but with a strong interest in biological systems — I focus on the structural fragmentation of metabolites in tandem MS spectra, thereby obtaining isotope distribution information to interpret alterations in biological systems.

By analyzing the isotopic atom distributions in different fragments, I have developed LC-MS methods to analyze position-specific isotope distributions (isotopomers) of glutamate and aspartate. Changes in isotope distribution can reflect variations in metabolomic flux within different systems, including: pyruvate carboxylation, pyruvate dehydrogenation, fumarate hydration, and malate dehydrogenation. This demonstrates that position-specific isotope analysis can provide valuable information not easily obtained from traditional tools. Further exploration of position-specific isotope information for other metabolites will enhance our toolbox for studying enzyme activities, metabolon assemblies, protein-RNA interactions, and other biological phenomena.

Feng Cai, Ph.D., received his B.Sc. in 1999 from Lanzhou University in China. He pursued his Ph.D. in glycochemistry from University of Illinois at Chicago and Wayne State University. In…
Full Bio

Select Publications

Cai, F., Bezwada, D., Cai, L., Mahar, R., Wu, Z., Chang, M., Pachnis, P., Yang, C., Kelekar, S., Gu, W., Brooks, B., Ko, B., Vu, H., Mathews, T. P., Zacharias, L. G., Martin-Sandoval, M., Do, D., Oaxaca, K. C., Jin, E. S., Margulis, V., Malloy, C. R., Merritt, M. E., and R.J. DeBerardinis. (2023). Comprehensive isotopomer analysis of glutamate and aspartate in small tissue samples. Cell Metabolism 35, 1830-1843. (PubMed)

Kim, J., Lee, H. M., Cai, F., Ko, B., Yang, C., Lieu, E., Muhammad, N., Rhyne, S., Li, K., Haloul, M., Gu, W., Faubert, B., Kaushik, A. K., Cai, L., Kasiri, S., Marriam, U., Nham, K., Girard, L., Wang, H., Sun, X., Kim, J., Minna, J. D., Unsal-Kacmaz, K., and R.J. DeBerardinis. (2020). The hexosamine biosynthesis pathway is a targetable liability in KRAS/LKB1 mutant lung cancer. Nature Metabolism 2, 1401-1412.(PubMed)

Gu, Z., Liu, Y., Cai, F., Patrick, M., Zmajkovic, J., Cao, H., Zhang, Y., Tasdogan, A., Chen, M., Qi, L., Liu, X., Li, K., Lyu, J., Dickerson, K. E., Chen, W., Ni, M., Merritt, M. E., Morrison, S. J., Skoda, R. C., DeBerardinis, R. J; Xu, J. (2019). Loss of EZH2 reprograms BCAA metabolism to drive leukemic transformation. Cancer Discovery 9, 1228-1247. (PubMed)

Cai, F., Thangada, N. D., Pan, E., Ready, J. M. (2013). On the Rapid Oxidation of Allene-containing Phosphines. Organometallics 32, 5619-5622. (acs.org)

Cai, F., Pu, X., Qi, X., Lynch, V., Radha, A., Ready, J. M. (2011). Chiral allene-containing phosphines in asymmetric catalysis. J. Am. Chem. Soc. 133, 18066-18069. (PubMed)

Tian, Y., Suk, D.-H., Cai, F., Crich, D., Mesecar, A. D. (2008). Bacillus anthracis o-succinylbenzoyl-CoA synthetase: reaction kinetics and a novel inhibitor mimicking its reaction intermediate. Biochemistry 47, 12434-12447. (PubMed)

Crich, D., Cai, F. (2007). Stereocontrolled glycoside and glycosyl ester synthesis. Neighboring group participation and hydrogenolysis of 3-(2′-Benzyloxyphenyl)-3, 3-dimethylpropanoates. Org. Lett. 9, 1613-1615. (PubMed)

Inside CRI Newsletter

Stay up-to-date with our latest discoveries and news by subscribing to our quarterly email newsletter.