Markus Delling, PhD

Asst Professor
Physiology
+1 415 476-2308
Research Overview: 

About four billion years ago, while earth was covered with a primordial soup enriched with the building blocks of life, the equal occurrence of chiral molecules (non-superimposable “left-handed” vs “right-handed” molecules) fell out of balance. As a consequence, today’s life is asymmetric.

In humans, our visceral organs such as heart, pancreas, and intestine are asymmetrically positioned along the left-right (L-R) axis. Essential key players in establishing L-R asymmetry are fluid flow, primary cilia, ion channels and the embryonic node. The key sensory organelle in L-R patterning is the primary cilium, a hair-like structure protruding from the plasma membrane of most mammalian cells and believed to function like an antenna. Early during development primary cilia utilize ciliary ion channels and electric signaling to “sense” directed fluid flow and orchestrate asymmetric gene expression and ultimately L-R patterning. The fundamental molecular mechanisms of how primary cilia sense their local environment, including the movement of fluids, are only poorly understood. Yet a plethora of severe human diseases such congenital heart disease, autosomal dominant polycystic kidney disease (ADPKD), obesity, and mental retardation can be attributed to improper cilia function.

My lab studies the molecular mechanisms of how primary cilia utilize ion channels and GPCRs to sense their local environment and control such important processes as left-right asymmetry formation. Major research goals in our lab include

  1. Identify the environmental signals that activate ciliary Ca2+ channels
  2. Understand cilia-dependent signaling cascades governed by electric signaling.
  3. Define the electric signaling within the embryonic node during early steps of establishing asymmetry.  
  4. Identify small molecule agonists and antagonists of ciliary ion channels as novel therapeutics for the treatment of ciliopathies such as ADPKD
  5. Understand the diversity of primary cilia signaling with respect to ion channel composition.

We use a variety of different approaches including mouse genetics, RNA sequencing, cutting edge primary cilia Ca2+ imaging, electrophysiology and biochemistry.

Primary Thematic Area: 
Cancer Biology & Cell Signaling
Secondary Thematic Area: 
Developmental & Stem Cell Biology
Research Summary: 
Calcium signaling in primary cilia during development and disease

Websites

Publications: 

Cellular aspect ratio and cell division mechanics underlie the patterning of cell progeny in diverse mammalian epithelia.

eLife

McKinley KL, Stuurman N, Royer LA, Schartner C, Castillo-Azofeifa D, Delling M, Klein OD, Vale RD

MCOLN1 is a ROS sensor in lysosomes that regulates autophagy.

Nature communications

Zhang X, Cheng X, Yu L, Yang J, Calvo R, Patnaik S, Hu X, Gao Q, Yang M, Lawas M, Delling M, Marugan J, Ferrer M, Xu H

Primary cilia are not calcium-responsive mechanosensors.

Nature

Delling M, Indzhykulian AA, Liu X, Li Y, Xie T, Corey DP, Clapham DE

Ion channels and calcium signaling in motile cilia.

eLife

Doerner JF, Delling M, Clapham DE