- 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 email@example.com.
Graduate and undergraduate students
(Lou X.) Methods Mol Biol. 2018;1847:95-108.
(Lou X.) Front Cell Neurosci. 2018;12:66.
(Ji C, Fan F, Lou X.) Cell Rep. 2017 08 08;20(6):1409-1421.
(Mahapatra S, Lou X.) J Physiol. 2017 01 01;595(1):193-206.
(Fan F, Funk L, Lou X.) J Neurosci. 2016 06 01;36(22):6097-115.
(Mahapatra S, Fan F, Lou X.) Proc Natl Acad Sci U S A. 2016 May 31;113(22):E3150-8.
(Ji C, Zhang Y, Xu P, Xu T, Lou X.) J Biol Chem. 2015 Nov 06;290(45):26978-93.
(Fan F, Ji C, Wu Y, Ferguson SM, Tamarina N, Philipson LH, Lou X.) J Clin Invest. 2015 Nov 02;125(11):4026-41.
(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.
(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.
(Raimondi A, Ferguson SM, Lou X, Armbruster M, Paradise S, Giovedi S, Messa M, Kono N, Takasaki J, Cappello V, O'Toole E, Ryan TA, De Camilli P.) Neuron. 2011 Jun 23;70(6):1100-14.
(Ji C, Lou X.) J Vis Exp. 2016 10 15(116).