Stormy Chamberlain

UConn Hosts Prader-Willi Stem Cell Biobank

Stem cells provided through a new biobank hosted at UConn will allow researchers around the world to better understand Prader-Willi syndrome and look for potential therapies for the rare genetic disease.

Stem cells provided through a new biobank hosted at UConn will allow researchers around the world to better understand Prader-Willi syndrome and look for potential therapies for the rare genetic disease.


A new collaboration between UConn Health and the Foundation for Prader-Willi Research will create a centralized, high-quality biobank of stem cells to help researchers better understand Prader-Willi syndrome, a rare genetic disease that may hold insights into obesity, developmental delays, autism spectrum disorders, and many other conditions.

The foundation (FPWR) and the UConn–Wesleyan University Stem Cell Core will jointly support the biobank of induced-pluripotent stem cells for Prader-Willi syndrome. These special stem cells are made from adult cells, and they have the potential to grow into any bodily tissue, including skin, stomach, brain, blood, and more. The biobank will be able to supply induced-pluripotent stem cells for Prader-Willi syndrome to researchers throughout the world.

Prader-Willi syndrome occurs in approximately 1 in 15,000 to 30,000 births. It’s caused when certain genes that are normally found on chromosome 15 are missing or not working. In most individuals with Prader-Willi syndrome, certain genes on chromosome 15 that should be specifically expressed from the father’s chromosome are missing. Geneticists don’t understand why, but the mother’s version of these genes is always turned off.

It’s these genes, and how their absence affects the rest of the genome’s and cells’ functions, that researchers will be able to investigate thanks to the biobank. Researchers will be able to use the induced-pluripotent stem cells to look for potential therapies for Prader-Willi syndrome. They may also be able to use the cells to explore the genetic and biomolecular basis of some of the syndrome’s symptoms, such as sleep disorders, developmental delays, and disordered eating.

UConn will host the centralized repository in the Stem Cell Core on the UConn Health medical school campus. Each Prader-Willi syndrome induced-pluripotent stem cell sample provided through the biobank will have undergone a select set of validation assays. The biobank will help facilitate research on cellular phenotypic abnormalities in Prader-Willi syndrome and ensure that precious research dollars are not spent re-creating stem cell resources that may already exist.

“The objective of FPWR’s translational research program is to reduce the amount of time and resources needed to move therapeutic studies forward,” says Nathalie Kayadjanian, director of translational research at FPWR. “Stem cells stored at the UConn Core will provide Prader-Willi syndrome researchers and pharmaceutical companies pursuing Prader-Willi syndrome therapeutics high-quality cellular resources to perform robust experiments in a timely manner.”

Currently the Prader-Willi syndrome biobank has two cell lines, one with a deletion of certain genes on the father’s copy of chromosome 15, the other with two copies of chromosome 15 from the mother and none from the father. Both cell lines were contributed by Stormy Chamberlain, Ph.D., and Marc Lalande, Ph.D., UConn Health researchers who study Prader-Willi syndrome and its sibling genetic disorder Angelman’s syndrome. More cell lines will be banked at the facility in the coming years.

Lab Notes – Summer 2017

Melanoma’s Signature

illustration of a melanoma cell

Dangerous melanomas likely to metastasize have a distinctive molecular signature, UConn Health researchers reported in the February issue of Laboratory Investigation. Melanomas are traditionally rated on their thickness; very thin cancers can be surgically excised and require no further treatment, while thick ones are deemed invasive and require additional therapies. But melanomas of intermediate thickness are harder to judge. The researchers measured micro-RNAs produced by melanoma cells and compared them with the micro-RNAs in healthy skin. Micro-RNAs regulate protein expression in cells. The team found that melanomas with the worst outcomes produced lots of micro-RNA21 compared to melanomas of similar thickness with better outcomes. In the future this molecular signature could help dermatologists decide how aggressively to treat borderline melanomas.


Chili Pepper and Marijuana Calm the Gut

The medical benefits of marijuana are much debated, but what about those of chili peppers? It turns out that when eaten, both interact with the same receptor in our stomachs, according to UConn Health research published in the April 24 issue of Proceedings of the National Academy of Sciences. The scientists found feeding mice chili peppers meant less gut inflammation and cured those with Type 1 diabetes. Why? The chemical capsaicin in the peppers bonds to a receptor found in cells throughout the gastrointestinal tract, causing the cells to make anandamide — a compound chemically akin to the cannabinoids in marijuana. The research could lead to new therapies for diabetes and colitis and opens up intriguing questions about the relationship between the immune system, the gut, and the brain.

illustration of chili peppers and marijuana in the gut


Isolating Their Target

brain scan

Brain cells of individuals with Angelman syndrome fail to mature, disrupting the ability of the cells to form proper synaptic connections and causing a cascade of other developmental deficits that result in the rare neurogenetic disorder, according to UConn Health research. Neuroscientist Eric Levine’s team used stem cells derived from Angelman patients to identify the disorder’s underlying neuronal defects, an important step in the ongoing search for potential treatments and a possible cure. Previously, scientists had relied primarily on mouse models that mimic the disorder. The findings were published in the April 24 issue of Nature Communications. While Levine’s team investigates the physiology behind the disorder, UConn developmental geneticist Stormy Chamberlain’s team researches the genetic mechanisms that cause Angelman.


The Cornea’s Blindness Defense

eye

The formation of tumors in the eye can cause blindness. But for some reason our corneas have a natural ability to prevent that from happening. Led by Royce Mohan, UConn Health neuroscientists believe they have found the reason, findings that will be detailed in September’s Journal of Neuroscience Research. They link the tumor resistance to a pair of catalytic enzymes called extracellular signal-regulated kinases 1 and 2. When ERK1/2 are overactivated in a specific type of cell, the “anti-cancer privilege of the cornea’s supportive tissue can be overcome,” says Mohan. That happens in the rare disease neurofibromatosis-1. “These findings may inform research toward developing better strategies for the prevention of corneal neurofibromas,” says Dr. George McKie, cornea program director at the National Eye Institute, which funded the study.