- Cell Membrane
- Clathrin-Coated Vesicles
- Diabetes Mellitus, Type 2
- Dynamin I
- Dynamin III
- Ion Channels
Methodologies and Techniques
- Cells, Cultured
- Live cell imaging: spinning disk confocal, TIRFM, FRET
- Mice, Knockout
- Microscopy, Electron, Transmission
- Molecular Biology
- Patch-Clamp Techniques
- sub-cellular optogenetics
- super-resolution microscopy (PALM, dSTORM, SIM, STED)
We are interested in neural communication in the brain. We study vesicle trafficking in neurons and neuroendocrine cells in health and disease. Our work is at the interface of neuroscience, cell biology, and biophysics. It is closely relevant to several human diseases that currently have no cure. Multiple cutting-edge approaches are utilized and developed in our study, including live-cell imaging (TIRF/Confocal), PALM/d-STORM, optogenetics, patch-clamp, and mouse models.
Synapses and Synaptopathy
Synapse is the corner stone for brain function. Synaptic transmission is essential for neural circuit to function properly. Accordingly, synaptopathy (a disruption of synaptic structure and/or function) has been increasingly implicated in numerous brain disorders, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease, epilepsy, autism, and schizophrenia. We study fundamental aspects of presynaptic terminals: mechanisms underlying transmitter release, plasticity, and synaptic vesicle (SV) trafficking. Our work promises to gain deep understanding of synapses and to develop novel treatments for brain diseases. We use the calyx of Held in the auditory brainstem circuit as a model of central synapses.
Insulin Granule Trafficking and Diabetes
Dense core vesicles (DCVs) control the release of hormones that are essential for diverse cell signaling and function. To study DCV trafficking, we use pancreatic beta cells, which are the sole source of insulin production in mammals; dysfunction of beta cells is a hallmark of diabetes. Our recent work discovers an endocytosis-dependent regulation of insulin secretion in beta cells, highlighting a potential link between beta cell endocytosis and diabetes.
Nano-machinery of Vesicle Trafficking
How exocytosis and endocytosis are coupled at nerve terminals? This question remains unclear despite decades of research on each process. Nearly all genes and molecules in exocytosis and endocytosis have been identified and characterized, however, we know very little about how these two fundamental events are coupled in time and space under physiological condition. Moreover, a clear picture of the molecular architecture of release sites (SNARE, docking/priming factors, Ca2+ sensors, and Ca2+ channels) at synaptic active zones is also missing. We are developing innovative tools, including single-molecule localization super-resolution microscopy (SMLM), to understand the structure, dynamics, and regulation of these nano-machines in central synapses.
We are recruiting:
Postdoctoral fellows: Applicants who have experience with patch-clamp, optical nanoscopy (TIRF/PALM/STORM/STED), or molecular biology are especially welcome to apply. Please send a succinct research plan (one page) and your CV to firstname.lastname@example.org.
Graduate and undergraduate students
(Lou X.) Methods Mol Biol. 2018;1847:95-108 PMID: 30129012 SCOPUS ID: 2-s2.0-85052248659 08/22/2018
(Lou X.) Front Cell Neurosci. 2018;12:66 PMID: 29593500 PMCID: PMC5861208 03/30/2018
(Lou X.) Protein-Lipid Interactions: Perspectives, Techniques and Challenges. 1 January 2018:107-132 SCOPUS ID: 2-s2.0-85049016121 01/01/2018
(Ji C, Fan F, Lou X.) Cell Rep. 2017 08 08;20(6):1409-1421 PMID: 28793264 PMCID: PMC5613661 SCOPUS ID: 2-s2.0-85026870735 08/10/2017
(Mahapatra S, Lou X.) J Physiol. 2017 01 01;595(1):193-206 PMID: 27229184 PMCID: PMC5199734 SCOPUS ID: 2-s2.0-84977537713 05/28/2016
(Ji C, Lou X.) J Vis Exp. 2016 10 15(116) PMID: 27805608 PMCID: PMC5092206 SCOPUS ID: 2-s2.0-84992505061 11/03/2016
(Fan F, Funk L, Lou X.) J Neurosci. 2016 06 01;36(22):6097-115 PMID: 27251629 PMCID: PMC4887570 SCOPUS ID: 2-s2.0-84971673132 06/03/2016
(Mahapatra S, Fan F, Lou X.) Proc Natl Acad Sci U S A. 2016 May 31;113(22):E3150-8 PMID: 27185948 PMCID: PMC4896691 SCOPUS ID: 2-s2.0-84971572911 05/18/2016
(Ji C, Zhang Y, Xu P, Xu T, Lou X.) J Biol Chem. 2015 Nov 06;290(45):26978-93 PMID: 26396197 PMCID: PMC4646391 SCOPUS ID: 2-s2.0-84946780726 09/24/2015
(Fan F, Ji C, Wu Y, Ferguson SM, Tamarina N, Philipson LH, Lou X.) J Clin Invest. 2015 Nov 02;125(11):4026-41 PMID: 26413867 PMCID: PMC4639984 SCOPUS ID: 2-s2.0-84946760942 09/29/2015
(Lou X, Fan F, Messa M, Raimondi A, Wu Y, Looger LL, Ferguson SM, De Camilli P.) Proc Natl Acad Sci U S A. 2012 Feb 21;109(8):E515-23 PMID: 22308498 PMCID: PMC3286982 SCOPUS ID: 2-s2.0-84863118882 02/07/2012
(Milosevic I, Giovedi S, Lou X, Raimondi A, Collesi C, Shen H, Paradise S, O'Toole E, Ferguson S, Cremona O, De Camilli P.) Neuron. 2011 Nov 17;72(4):587-601 PMID: 22099461 PMCID: PMC3258500 SCOPUS ID: 2-s2.0-81355153885 11/22/2011