Sanders Lab

Mission

The mission of my laboratory is to understand how visceral smooth muscle organs produce the contractile patterns necessary for gastrointestinal motility and urinary functions. We work with tissues from animal models and human patients when possible.

Key areas of focus

Smooth muscle biology; effects of transmitters, hormones and other endogenous chemicals on electrical and mechanical events. Mechanistic basis for gastrointestinal motility and bladder function. We study voltage and drug-dependent membrane excitability mechanisms in smooth muscles. Second messenger regulation of ionic channels. We have worked out the mechanisms of electrical rhythmicity and propagation of excitable events in smooth muscles and interstitial cells. We measure dynamic Ca2+ signaling in smooth muscle cells and interstitial cells in situ using optogenetic sensors expressed in a cell specific manner in the cells of interest. We have also studied the role of the enteric and autonomic nervous systems in regulating smooth muscle electrical and mechanical patterns. We have demonstrated the anatomical relationships between nerve terminals and smooth muscle cells and interstitial cells. We have also characterized the functional genomics of the neuromuscular apparatus, known as the SIP syncytium, in visceral smooth muscles.

Lab team

My lab is integrated through 2 multi-PI grants with the labs of Sean Ward and Sal Baker. Major investigators within our groups are Sung Jin Huang (Research Associate Professor), Ji Yeon Lee (Research Assistant Professor), Allison Bartlett (Post-doctoral fellow). Several undergraduate students are also typically working in the labs

Notable research findings

My research has focused on the study of the pacemaker and neuro-effector mechanisms in visceral smooth muscles. My lab has extensive experience isolating cells to study basic mechanisms of interstitial cells and investigating physiological regulation provided by unique cell types in smooth muscle tissues. We were the first to isolate and record from interstitial cells of Cajal, PDGFRα+ cells and GI resident macrophages. We determined cell-specific markers, exploiting immunological techniques, genetic engineering and endocytosis mechanisms, to identify specific types of cells in complex tissues and mixed cell dispersions. We adapted flow cytometry and fluorescence-activated cell sorting to quantify relative numbers of cells, purify specific populations of cells dispersed from GI muscles and collect cells from these tissues for genome-wide expression analyses. A broad range of physiological and morphological techniques have been used to evaluate structure, distribution, cell-to-cell interactions and functions of interstitial cells in intact tissues and organs. Recent work has used optogenetic techniques to monitor Ca2+ signaling dynamics of cells within intact muscle tissues.

Equipment, technology and techniques

  • We have several patch clamp setups that measure the activity of ion channels in cell membranes
  • We have more traditional intracellular electrophysiology equipment to impale cells within muscles and make transmembrane measurements of electrical behaviors and responses to neurotransmitters, hormones and paracrine substances.
  • We have several imaging setups that combine confocal microscopy with fluorescence measurements of Ca2+ signaling.
  • We also have a variety of biochemical tools to isolate and measure mRNA and proteins.

Active grants and research projects

  1. Mechanism of action of gastric interstitial cells of Cajal.
    • Award: R01 DK120759 (Multi-PI with Sal A. Baker)
    • Funding organization: National Institutes of Health (NIDDK)
  2. Role of interstitial cells in patterned colonic motor activity
    • Award: R01 DK120759 (Multi-PI with Sal A. Baker)
    • Funding organization: National Institutes of Health (NIDDK)
  3. Control of motility in lower esophageal sphincter.
    • Award: R01 DK129528 (Co-PI; PI is Caroline Cobine)
    • Funding organization: National Institutes of Health (NIDDK)
  4. Novel targets for GI hormones and neuropeptides.
    • Award: R01 DK143049 (Co-PI; PI is Sal A. Baker)
    • Funding organization: National Institutes of Health (NIDDK)