Royce Mohan

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 2017

For MRSA, Resistance is Futile

UConn medicinal chemists have designed experimental antibiotics that kill Methicillin-resistant Staphylococcus aureus (MRSA), a common and often deadly bacteria that causes skin, lung, and heart infections. The new antibiotics disable the bacteria’s vitamin B9 enzyme. Without vitamin B9, the bacteria can’t make essential amino acids and they die. Not only do the new antibiotics kill regular MRSA, they also kill types of the bacteria with unusual antibiotic-resistance genes that had never been seen before in the U.S. And that’s no accident: the chemists designed the antibiotics to latch on to the enzyme so cleverly that if it changed enough to elude them, it would no longer be able to do its job with vitamin B9. This could make the new antibiotics resistant to, well, resistance. The research was published in the Dec. 22, 2016 issue of Cell Chemical Biology.

MRSA colonies are shown on a blood agar plate.


State’s Leading Institutions Launch International Effort to Advance Metabolic Research

overweight 3D model running with target on metabolic area

UConn, Yale University, and The Jackson Laboratory (JAX) have partnered with the Weizmann Institute of Science, a prestigious counterpart in Israel, to fill a research void in metabolic diseases that affect billions of people worldwide. The goal of the newly formed Metabolic Research Alliance is to unite the expertise of the institutions on research projects that swiftly move investigations into clinical application and commercialization. The Alliance will employ a novel approach to coordinating existing and new expertise in the areas of immunology, cell biology, microbiota, and the rapidly evolving field of genomics. While investigations will initially focus on obesity and diabetes, the research projects will eventually pursue solutions to additional metabolic diseases.


Innovative Imaging Could Save Sight

Connecticut Innovations has awarded $500,000 to a team of UConn researchers to speed the process to commercialization of the biomarker probe they’re developing to detect a precursor to blindness. The team — led by Royce Mohan, associate professor of neuroscience at UConn Health, and including assistant professor of neuroscience Paola Bargagna-Mohan and UConn School of Pharmacy medicinal chemistry professor Dennis Wright — is developing a fluorescent small molecule imaging reagent to help identify preclinical stages of ocular fibrosis, which is associated with an aggressive form of age-related macular degeneration (AMD) that causes rapid vision loss. AMD is the leading cause of blindness in the U.S. The method would both enable earlier intervention and allow physicians to monitor the progress and effectiveness of interventions before it’s too late.


DOACs Safer Than Warfarin, Study Shows

Patients who suffered blunt traumatic intracranial hemorrhage (ICH) associated with direct oral anticoagulants (DOACs) had significantly lower mortality rates and lower rates of operative intervention compared with a similar group taking warfarin, a study published in the November issue of Trauma and Acute Surgery by researchers from UConn, Saint Francis Hospital and Medical Center, and Trinity College shows. Although DOACs have been an increasingly popular alternative to warfarin for anticoagulation, physicians have worried their use might lead to an increase in patient mortality from uncontrollable bleeding, according to the study. The study, based on data on 162 patients in the St. Francis Trauma Quality Improvement Program database, aimed to help close a gap in research on DOAC safety.

bloodclot in vein