Ph.D., SUNY at Buffalo, 1997
There are two current research areas in the lab: 1) regulation of excitability of the brain, 2) biology of endosomes and lysosomes. Both of the areas focus on the functional contributions of ion channel proteins. Please see lab website for details, https://web.sas.upenn.edu/ren-lab/.
Excitability of the brain: The brain uses electrical signals to control essentially every aspect of our life: from breathing to walking and intellectual reasoning. A major focus in the lab is on the molecular mechanisms by which neuronal excitability and the associated heterogeneity in brain regions are regulated. Along this line, we discovered the NALCN-UNC80-UNC79 protein complex that forms the major sodium-leak channel through which extracellular ions (Na+ and Ca2+) and neuropetides regulate neuronal excitability. Mutations in the complex lead to severe intellectual disability.
Organelle biology: A hallmark of eukaryotic cells is the separation of cellular functions in membrane-bound organelles in the cytosol. Intracellular membranes constitute >90% of total cell membrane, but their properties are generally less well defined in comparison with plasma membrane. We use biophysical, biochemical, structural and genetic approaches to define the biophysical properties and physiological roles of endosomal and lysosomal membrane proteins.
BIOL436, Molecular Physiology
BIOL444, Molecular Evolution of Physiological Functions
SELECTED PUBLICATIONS
See https://web.sas.upenn.edu/ren-lab/publications/ for an updated list.
Guo, J., Zeng, W., Chen, Q. Lee, C., Chen, L. Yang, Y., Cang, C., Ren, D. and Jiang, Y. (2016) Structure of the voltage-gated two-pore channel TPC1 from Arabidopsis thaliana. Nature 531: 196-201 (http://www.ncbi.nlm.nih.gov/pubmed/26689363)
Stray-Pedersen, A., Jan-Maarten Cobben, Trine E. Prescott, T.E, Lee, S., Cang, C., Aranda, K., Ahmed, S., Alders, M., Gerstner, T., Aslaksen, K., Tétreault, M., Qin, W., Hartley, T., Jhangiani, S.N., Muzny, D.M., Maja Tarailo-Graovac, Clara DM van Karnebeek, Care4Rare Canada Consortium, Baylor Hopkins Center for Mendelian Genomics, Lupski, J.R., Ren, D.* and Yoon, G.* (2015) Biallelic mutations in UNC80 cause persistent hypotonia, encephalopathy, growth retardation, and severe intellectual disability. Am J Hum Genet 98: 202-209. (http://dx.doi.org/10.1016/j.ajhg.2015.11.004)
Cang, C., Aranda, K., Seo, Y.-J., Gasnier, B. and Ren, D. (2015) TMEM175 is an organelle K+ channel regulating lysosomal function. Cell 162: 1101-1112 (http://www.ncbi.nlm.nih.gov/pubmed/26317472)
Flourakis, M., Kula-Eversole, E., Hutchison, A.L., Han, T.H, Aranda, K., Moose, D.L., White, K.P., Dinner, A.R., Lear, B.C., Ren, D, Diekman, C.D., Raman, I.M., and Allada, R. (2015) A Conserved bicycle model for circadian clock control of membrane excitability. Cell 162: 836-848 (http://www.ncbi.nlm.nih.gov/pubmed/26276633)
Xu, H. and Ren, D. (2015) Lysosomal Physiology. Annu. Rev. Physiol. 77:57-80 (http://www.ncbi.nlm.nih.gov/pubmed/25668017)
Cang, C., Bekele, B. and Ren, D. (2014) The voltage-gated sodium channel TPC1 confers endolysosomal excitability. Nature Chem. Biol. 10: 463-469 (http://www.ncbi.nlm.nih.gov/pubmed/24776928)
Cang, C., Aranda, K. and Ren, D. (2014) A non-inactivating high-voltage-activated two-pore Na+ channel that supports ultra-long action potentials and membrane bistability. Nature Commun. 5: 5015, DOI: 10.1038/ncomms6015 (http://www.ncbi.nlm.nih.gov/pubmed/25256615)
Cang, C.*, Zhou, Y.*, Navarro, B., Aranda, K., Shi, L., Battaglia-Hsu, S., Nissim, I., Clapham, D. and Ren, D. (2013) mTOR Regulates Lysosomal ATP-sensitive Two-Pore Na+ Channels to Adapt to Metabolic State. Cell 152: 778-790 (http://www.ncbi.nlm.nih.gov/pubmed/23394946)
Wang, X., Zhang, X., Dong, X.-P., Samie, M., Li, X., Cheng, X., Goschka, A., Shen, D., Zhou, Y., Harlow, J., Zhu, M.-X., Clapham, D.E., Ren, D., and Xu, H. (2012) TPC proteins are phosphoinositide-activated sodium-selective ion channels in endosomes and lysosomes. Cell 151:372-383 (http://www.ncbi.nlm.nih.gov/pubmed/23063126)
Ren, D. (2011) Sodium leak channels in neuronal excitability and rhythmic behaviors. Neuron 72: 899-911 (http://www.ncbi.nlm.nih.gov/pubmed/22196327)
Lishko, P., Kirichok, Y., Ren, D., Navarro, B., Chung, J.-J., and Clapham, D.E. (2011) The control of male fertility by spermatozoan ion channels. Annu. Rev. Physiol. 74: 453-475 (http://www.ncbi.nlm.nih.gov/pubmed/22017176)
Ren D. (2010) Sperm and the proton channel. N Engl J Med 362: 1934-5 (http://www.ncbi.nlm.nih.gov/pubmed/20484401)
Lu B, Zhang Q, Wang H, Wang Y, Nakayama M, Ren D (2010) Extracellular Calcium Controls Background Current and Neuronal Excitability via an UNC79-UNC80-NALCN Cation Channel Complex. Neuron 68:488-499 (http://www.ncbi.nlm.nih.gov/pubmed/21040849)
Ren D. and Xia J. (2010) Calcium signaling through CatSper channels in mammalian fertilization. Physiology 25: 165-75 (http://www.ncbi.nlm.nih.gov/pubmed/20551230)
Lu, B.*, Su, Y.*, Das, S., Wang, H., Wang, Y., Liu, J. and Ren, D. (2009) Peptide neurotransmitters activate a cation channel complex of NALCN and UNC-80. Nature 457:741-744 (http://www.ncbi.nlm.nih.gov/pubmed/19092807)
Xia, J. and Ren, D. (2009) Egg coat proteins activate Ca2+ entry into mouse sperm via CatSper channels. Biol. Reprod. 80:1092-1098 (http://www.ncbi.nlm.nih.gov/pubmed/19211808)
Liu, J., Xia, J., Cho, K-H., Clapham, D.E. and Ren, D. (2007) CatSperβ, a novel transmembrane protein in the CatSper channel complex. J. Biol. Chem. 282: 18945-18952. (http://www.ncbi.nlm.nih.gov/pubmed/17478420)
Lu, B., Su, Y., Das, S., Xia, J., Liu, J. and Ren, D. (2007) The neuronal NALCN channel contributes resting sodium permeability and is required for normal respiratory rhythm. Cell 129: 371-378. (http://www.ncbi.nlm.nih.gov/pubmed/17448995)