1997 – 2001 Peking University, B.S.

2001 – 2007 Yale University, Ph.D.

2007 - 2015 Johns Hopkins University, Postdoctoral Fellow and Research Associate

2016- Institute of Biophysics, CAS, Principle Investigator

Our research focuses on understanding the conserved mechanisms underlying macropinocytosis and cell migration, two processes that share many common features yet fulfil different physiological functions. In particular, we aim to elucidate how cells achieve polarized state during these two highly dynamic cellular processes, how polarly distributed signaling and cytoskeleton machineries coordinate to drive morphological changes, how cells modulate macropinocytosis and migration in response to environmental cues, and how the two processes regulate cell physiology. Our strategy is to use the powerful genetic, cell biology, and biochemical tools available in the model organismDictyostelium discoideumto gain insights and to further test these concepts in higher eukaryotic cells.

UsingDictyostelium discoideumand mammalian cells as models, we have established biochemical and genetic methods for systematic identification of novel regulators of macropinocytosis and migration and carried out detailed analyses to elucidate their function and regulatory mechanisms. We have uncovered how phosphoinositide signaling and actin cytoskeleton coordinate to drive the morphogenesis of pseudopodia and macropinocytic cups (Yang et al.,J Cell Biol, 2021), how a Rab GAP cascade ensures programmed Rab switch during macropinosome maturation (Tu et al.,Nat Commun, 2022), and how an oligopeptide transporter constitutes a positive feedback mechanism regulating macropinocytosis (Zhang et al.,J Cell Sci, 2022). Further, we have explored anti-cancer therapeutics by targeting pathways critical for macropinocytosis (Jiao et al.,PNAS, 2020). These studies allowed us to gain fresh insights into the formation of leading and trailing edge structures in cells undergoing macropinocytosis or directed migration, the organization of macropinocytic pathway, and the interrelationship between nutrient conditions and macropinocytosis regulation.

Both macropinocytosis and migration have profound implications for human health. By defining the key regulators involved in these processes, their functions, and the various mechanisms by which they are spatiotemporally regulated, we hope to eventually extend our research to elucidate the basis of human diseases and to develop therapeutic strategies by specifically targeting these pathways.

1. Tu H, Wang Z, Yuan Y, Miao X, Li D, Guo H, Yang Y,Cai H. (2022) The PripA-TbcrA complex-centered Rab GAP cascade facilitates macropinosome maturation in Dictyostelium.Nature Communications. 13(1):1787.

2. Zhang Y^#, Tu H^#, Hao Y, Li D, Yang Y, Yuan Y, Guo Z, Li L, Wang H*,Cai H*. (2022) Oligopeptide transporter Slc15A modulates macropinocytosis inDictyosteliumby maintaining intracellular nutrient status.Journal of Cell Science. 135(7):jcs259450. (*corresponding)Highlighted in JCS.

3. Li D, Sun F, Yang Y, Tu H,Cai H. (2022) Gradients of PI(4,5)P₂and PI(3,5)P₂jointly participate in shaping the back state ofDictyosteliumcells.Frontiers in Cell and Developmental Biology. 10:835185.

4. Yang Y*, Li D*, Chao X, Singh SP, Thomason P, Yan Y, Dong M, Li L, Insall RH,Cai H. (2021) Leep1 interacts with PIP₃and the Scar/WAVE complex to regulate cell migration and macropinocytosis.Journal of Cell Biology. 220(7):e202010096.Highlighted in JCB.

5. Zhuang Y, Zuo D, Tao Y,Cai H*, Li L*. (2020) Laccase3-based extracellular domain provides possible positional information for directing Casparian strip formation in Arabidopsis.PNAS. 117(27):15400-t. (*corresponding)

6. Jiao Z,Cai H*, Long Y, Sirka O, Padmanaban V, Ewarld AJ, Devreotes PN*. (2020) Statin-induced GGPP depletion blocks macropinocytosis and starves cells with oncogenic defects.PNAS. 117(8):4158-4168. (*corresponding)

7. Zhan H, Bhattacharya S,Cai H, Iglesias PA, Huang CH, Devreotes PN. (2020) An Excitable Ras/PI3K/ERK Signaling Network Controls Migration and Oncogenic Transformation in Epithelial Cells.Developmental Cell. 54(5):608-623.

8. Edwards M,Cai H, Abubaker-Sharif B, Long Y, Lampert TJ, Devreotes PN. (2018) Insight from the maximal activation of the signal transduction excitable network in Dictyostelium discoideum.PNAS. 115(16):E3722-3730.

9. Miao Y, Bhattacharya S, Edwards M,Cai H, Inoue T, Iglesias PA, Devreotes PN. (2017) Altering the threshold of an excitable signal transduction network changes cell migratory modes.Nature Cell Biology. 19(4):329-340.

10. Senoo H,Cai H, Wang Y, Sesaki H, Iijima M. (2016) The Novel RacE Binding Protein GflB Sharpens Ras Activity at The Leading Edge of Migrating Cells.Molecular Biology of the Cell. 27(10):1596-1605.

11. Hoeller O^#, Toettcher J^#,Cai H, Sun Y, Huang CH, Freyre M, Zhao M, Devreotes PN, Weiner O. (2016) Gβ regulates coupling between actin oscillators for cell polarity and directional migration.PLOS Biology. 14(2):e1002381.

12. Ding J, Segarra VA, Chen S,Cai H, Lemmon SK, Ferro-Novick S. (2016) Auxilin facilitates membrane traffic in the early secretory pathway.Molecular Biology of the Cell. 27(1):127-136.

Before IBP

13. Santhanam B,Cai H, Devreotes PN, Shaulsky G, and Katoh-Kurasawa M. (2015) The GATA transcription factor GtaC regulates early developmental gene expression dynamics inDictyostelium.Nature Communications. 6:7551.

14.Cai H, Katoh-Kurasawa M, Muramoto T, Santhanam B, Long Y, Li L, Ueda M, Iglesias PA, Shaulsky G, Devreotes PN. (2014) Nucleocytoplasmic shuttling of a GATA transcription factor functions as a development timer.Science. 343(6177): research article 1249531.

15.Cai Hand Devreotes PN. (2011) Moving in the right direction: How eukaryotic cells migrate along chemical gradients.Seminars in Cell and Developmental Biology. 22(8):834-841.

16.Cai H, Das S, Kamimura Y, Long Y, Parent CA, Devreotes PN. (2010) Ras-mediated activation of the TORC2-PKB pathway is critical for chemotaxis.Journal of Cell Biology. 190(2):233-245.

17.Cai H, Reinisch K, Ferro-Novick S. (2007) Coats, Tethers, Rabs, and SNAREs work together to mediate the intracellular destination of a transport vesicle.Developmental Cell. 12(5):671-682.

18.Cai H, Yu S, Menon S, Cai Y, Lazarova D, Fu C, Reinisch K, Hay JC, Ferro-Novick S. (2007) TRAPPI tethers COPII vesicles by binding the coat subunit Sec23p.Nature. 445(7130):941-944.

19.Cai H, Zhang Y, Pypaert M, Walker L and Ferro-Novick S. (2005) Mutants intrs120disrupt traffic from the early endosome to the late Golgi.Journal of Cell Biology. 171(5):823-833.

(From Huaqing Cai, April 18, 2022)