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Xuelin-Lou

Xuelin Lou, PhD

Professor

Locations

  • Cell Biology, Neurobiology & Anatomy

Contact Information

Research Areas of Interest

  • Membrane Biophysics: Membrane Fusion, Membrane Fission, Membrane Trafficking, and Trafficking-associated Human Diseases.
  • Pancreatic Beta Cells, Diabetes
  • Super-resolution Imaging, Nanoscopy
  • Synapse Degeneration, Neurodegeneration, Alzheimer's Disease, and Parkinson's Disease
  • Synapse, Presynaptic Mechanisms, Synaptic Transmission, Synaptic Plasticity, and Synaptopathy

Research Experience

  • Actin Cytoskeleton
  • Autophagy, Autolysosome, lysosome
  • Calcium Signaling
  • Diabetes Mellitus, Type 2
  • Dynamin-1, Dynamin-2, Dynamin-3, Dynamin-Related Protein 1 (Drp1)
  • Endocytosis
  • Endophilin
  • Exocytosis
  • Ion Channels
  • Islets of Langerhans
  • Mice, Knockout
  • mitochondria

Methodologies and Techniques

  • Beta cells, islets, primary beta cell and islet cultures
  • Electron microscopy, EM tomography, volume EM (FIB-EM, FSB-EM)
  • Live cell imaging: spinning disk confocal, TIRFM, FRET
  • Molecular Biology
  • mouse genetics, disease models, AD models, PD models
  • Neurons, primary neuronal cultures, acute brain slices
  • Patch-Clamp Techniques
  • Presynaptic Capacitance Recordings, Real-time Capacitance.
  • Single Molecule Imaging
  • Sub-cellular optogenetics to manipulate vesicle docking
  • Super-resolution Microscopy (PALM, dSTORM, SIM, STED, ExM, MinFLUX)
  • Synaptic Ca2+ photolysis, synaptic Ca2+ imaging, secretion imaging.

Leadership Positions

  • Director, Advanced Cell Imaging Core

Research Interests

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 xulou@mcw.edu.

Graduate and undergraduate students

Publications