Spencer Vision Laboratory
SUNY Upstate in Syracuse, NY
The Spencer Lab studies how vision is performed at the molecular level.
How are the light-sensitive organelles of photoreceptors built?
The light sensing organelle of vertebrate photoreceptor cells is a modified primary cilium, called the outer segment. The outer segment houses hundreds of flattened, light sensitive membrane “discs” that enable this organelle to detect as little of light as a single photon. Photoreceptor cells continuously renew their disc membranes and defects in this process cause blindness in humans. A major goal of the Spencer lab is to understand the molecular mechanisms driving the morphogenesis of the outer segment and renewal of disc membranes with the ultimate objective to elucidate novel therapies for blindness in humans.
What is the role of photoreceptor-derived extracellular vesicles?
A striking feature associated with many cases of retinal degeneration is the accumulation of photoreceptor-derived extracellular vesicles. While vesicle accumulation generally correlates with photoreceptor cell death, the significance of these vesicles towards disease progression is unknown. Our lab is unraveling the basic molecular mechanisms leading to the release and clearance of these vesicles — first steps to understanding their precise role in the patholobiology of retinal degeneration.
How is PRCD involved in photoreceptor disc formation?
PRCD is a small protein which specifically resides in photoreceptor disc membranes and is necessary for maintaining the high fidelity of disc formation. Without PRCD, disc formation is error prone and a fraction of disc membrane material is released in the form of extracellular vesicles that aberrantly accumulate around photoreceptors. Little is known about how PRCD functions at the molecular level during disc formation and the Spencer Lab is addressing this knowledge gap using a variety of cell biological and biochemical techniques. Mutations in PRCD cause blindness in humans and are among the most common causes of blindness in dogs. Our goal is to understand the basic molecular mechanisms underlying PRCD’s function in photoreceptors and the retinal pathobiology caused by mutation in PRCD — the first steps towards developing future therapies to fight blindness associated with PRCD mutation.
Photoreceptor disc formation
In a process which is crucial for vision, each of your photoreceptor cells builds a new disc membrane every ~20 minutes. Polymerization of branched actin filaments at the site of disc formation is crucial for the process.
Our expertise
Electron microscopy – We use transmission and scanning electron microscopes to resolve photoreceptor cells at nanoscale resolution. Dr. Spencer is the scientific co-director of the electron microscopy facility at SUNY Upstate (click here to learn more).
Mass spectrometry – We combine traditional biochemical purification with advanced quantitative proteomics to elucidate the protein machinery crucial for building and maintaining photoreceptor cells. We collaborate with the mass spec core facility which is equipped with a high-end Orbitrap mass spectrometer (click here to learn more).
Light microscopy – Our lab has an ECHO spinning disc confocal microscope which we use to take multi-channel high resolution 3D images of photoreceptors. We also manage and share an IMARIS image analysis workstation with the Center for Vision Research.
Flow cytometry and cell sorting – We take advantage of the shared SONY SH800 cell sorter and analyzer, which is located only ~20 feet from the Spencer lab, to sort retinal cells for downstream applications ranging from mass spectrometry to single cell sequencing (10x genomics machine is adjacent).
Basic biochemistry and molecular biology – We use a plethora of basic cell biology and biochemistry techniques to study the cells, proteins and lipids crucial for vision.