The Jackson Laboratory

Old Drug, New Hope for Pediatric Brain Cancer

Dr. Ching C. Lau sees a patient.

Dr. Ching C. Lau sees a patient.


Some drugs for heart disease might also work against brain cancer, according to an analysis by researchers from The Jackson Laboratory (JAX), Connecticut Children’s Medical Center, and UConn Health. The researchers used a new approach to identify five heart medicines that might also be effective at fighting the most common type of childhood brain cancer, they report in Science Translational Medicine.

Medulloblastoma is the most common malignant brain tumor in children, accounting for 20 to 25 percent of pediatric brain tumors. Current treatments have significantly increased the survival rate, but many children face difficult side effects that impact their brains, hormones, and fertility for the rest of their lives. There are also a handful of patients who either don’t respond to available treatment options or suffer and die from relapses.

To quicken the long route to developing cancer drugs, the research team used a process called drug repositioning, reanalyzing drugs previously approved by the FDA and looking for crossover among the diseases that a drug is likely to treat. Using computational modeling methods, they compared approved drugs’ effects on gene expression profiles — that is, what genes they work with or against — to the genes active in patients with various diseases.

But medulloblastoma tumors are complex and often very different from patient to patient, and even internally in a single patient. Dr. Ching C. Lau thought drug repositioning could work to find better drugs for medulloblastoma, but suspected the technique could be improved. Lau, who is jointly appointed as a professor at JAX, UConn Health, and Connecticut Children’s Medical Center, heads the division of pediatric hematology-oncology at UConn Health and is the medical director of hematology-oncology at Connecticut Children’s.

Lau worked with a team of researchers from those institutions, as well as from Houston Methodist Research Institute and Texas Children’s Hospital, to devise a new integrated drug repositioning method that could work against something as complicated as medulloblastoma.

Their new method has identified eight drugs as possible medulloblastoma-fighting agents, including three already used as chemotherapy against other cancers and five previously used to treat heart failure.

The researchers also showed that one of the heart drugs, digoxin, helped mice with medulloblastomas live longer. The mice survived even longer when digoxin was combined with radiation.

“This is exciting because not only can we potentially improve overall survival of medulloblastoma patients with digoxin, but the results also suggest that we could potentially reduce the dose of radiation necessary when combined with digoxin, and thereby minimize long-term side effects of radiation among the survivors,” says Lau. “Because digoxin has been used for so many years to treat heart failure, its potential side effects are well known, and could potentially help speed up the subsequent clinical trial.”

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