Proceedings of the National Academy of Sciences

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.

Lab Notes – Spring 2016

Studying Dirty Diapers for Clues About Premature Babies

A team of UConn researchers is working on minimizing stress for premature babies by analyzing one of the most extensive sources of information these patients provide: poop. Fully one in nine babies born in the U.S. arrives prematurely, and the measures necessary to keep them alive are numerous, often painful, and may have long-term effects, including lower IQs and neurodevelopmental challenges. In an ongoing study by nursing professor Xiaomei Cong and microbiologist Joerg Graf, preemies’ fecal samples are collected to study each patient’s microbiome. The researchers chart the patterns in the gut microbiome and compare them to the babies’ daily procedures, medications, feeding, and parental contact, looking for correlations between microbiome dynamics and babies’ outcomes.


Researchers Pinpoint Bone Disease-causing Gene

Fragile bones are usually an old person’s affliction, but sometimes children are born with them. Hajdu-Cheney is a particularly terrible form of inherited bone disease, in which sufferers’ bones begin to soften and fracture early, often in childhood. Now, a team of researchers led by Dr. Ernesto Canalis, director of the Center for Skeletal Research at UConn Health, has shown in mice that a specific gene can cause the disease. Overabundant bone-absorbing cells may be causing the characteristic bone loss, the researchers reported in the Jan. 22 issue of The Journal of Biological Chemistry. The researchers hope to find a potential treatment, perhaps by slowing the development or activity of the cells that absorb old bone.


Researchers up one in antibacterial cat-and-mouse game

UConn pathobiologists have discovered that vibrio bacteria have a special protein that sounds the alarm when it detects antibiotics in the beta-lactams family, such as penicillins and cephalosporins. The protein, called histidine kinase, alerts the bacteria to produce an antibiotic-fighting enzyme called beta-lactamase. The researchers reported their discovery in the Feb. 1 edition of Proceedings of the National Academy of Sciences. They don’t yet know the mechanism for how the protein senses antibiotics, but now that they know it exists, they will work on a way to disable it by developing drugs that can desensitize the bacteria — so that they don’t respond to the alarm.


Diagnose sickle cell disease with your phone

A few drops of blood inserted into a tube on a smartphone could be all that’s necessary to diagnose sickle cell disease, UConn biomedical engineers reported in Scientific Reports on Oct. 22. A hereditary disease, sickle cell affects people across Africa and the U.S. If undiagnosed, it can cause silent strokes and life-long damage, but current techniques for screening newborns are cumbersome and require specialized training. UConn’s Stephanie Knowlton and Savas Tasoglu, working with colleagues at Yale, MIT, and Harvard, have invented a sickle cell testing device that can be plugged into an Android phone and easily interpreted by a non-specialist. They’re now working on expanding the device to work for other diseases.

A device to analyze blood for sickle cell disease