Michael J. Rindler, PhD

Associate Professor; Department of Cell Biology

RESEARCH THEMES:
Cell Biology

 

 

 

 

 

 

Contact Information

550 First Avenue
Medical Science Building
Floor 6, Room 627
New York, NY 10016

Tel: 212-263-5812
Email: michael.rindler@nyumc.org

Research Summary

The research in the laboratory is focused on the regulation of membrane protein trafficking in bladder urothelial cells, cardiac myocytes, and pancreatic acinar cells.

Uroplakins are a family of bladder-specific membrane proteins that accumulate in a post-Golgi vesicular compartment and assemble into 2D crystals that have the appearance of asymmetric unit membranes (AUMs). AUMs cover the whole surface of storage organelles called fusiform vesicles which belong to the class of lysosome-related organelles. Fusiform vesicles can fuse in a regulated fashion with the apical membrane of urothelial umbrella cells and cause the expansion of the membrane and thereby protecting the cells from the effects of bladder stretch. Our research is concerned with the elucidation of mechanisms that function in the delivery of these highly specialized vesicles to the apical surface of the bladder epithelium. We have evidence that the process is controlled by Rab27b, a member of the Rab family of GTPases that regulate vesicle trafficking, and by the SNARE protein VAMP8, which is involved in membrane fusion. We are investigating the Rab and VAMP binding partners that mediate the rapid and specific insertion of AUMs into urothelial umbrella cell apical membranes.

Cardiac muscle cells (myocytes) often die when exposed to hypoxic conditions, such as those caused by the interruption of blood flow (ischemia) during heart attacks. KATP channels, a specific class of potassium channels, play an critical role in mitigating the effects of hypoxia and promoting the viability of cardiac myocytes. We have discovered that a large reservoir of these potassium channels is found in intracellular vesicles in a cardiomyocytes and can be recruited to the plasma membrane in response to hypoxic conditions. We are now exploring the mechanisms by which this recruitment occurs in the heart and protects it against the effects of ischemia.

Epithelial cells from exocrine organs, such as the pancreas and salivary glands, produce and secrete many important proteins, including hydrolytic enzymes and growth factors. These secretory products are stored in granules and released by exocytosis, the fusion of the granule with the plasma membrane, when the cell is exposed to specific hormones and neurotransmitters. We are determined the protein composition of pancreatic zymogen granule membranes using mass spectrometry. In this way, we have discovered of a number of new proteins that we hypothesize are involved in granule exocytosis, biogenesis, and function. We are using cellular and animal models to elucidate the role of these new proteins in pancreatic secretion and in protecting the tissue from the effects of pancreatitis.