From Dab2 to Flab

More than 20 years ago, Sylvester Comprehensive Cancer Center researcher Xiang-Xi Michael Xu, who is also a professor of cell biology at the Miller School of Medicine, discovered Dab2, a protein long linked to cancer. He has studied its relationship to the disease ever since. Now he’s found that Dab2 also could have implications for fighting obesity. In a paper published in the journal Scientific Reports, the Xu lab showed that young mice without Dab2 don’t gain weight when given excessive food. In normal mice, Dab2 suppresses Ras-MAPK, which in turn elevates a protein called PPAR, which helps fat stem cells make the leap to mature fat cells, causing them to pack on weight. Eliminating Dab2 short-circuits that process, keeping Dab2-deficient mice lean. But as the mice mature, the metabolic effect dissipates, and the loss of Dab2 has virtually no effect. Xu believes this is because mice (and humans) lose their fat stem cells as they reach maturity. “Dab2 controls a population of fat stem cells that slowly disappears,” said Xu. “It seems that children are especially affected by diet. They can both increase fat cell number and fat cell size when they are young. Later in life, they can still make fat, but that’s existing fat cells getting bigger. Habits of childhood could be affecting adults, making them more susceptible to obesity.” These findings may reinforce the importance of steering children away from high-fat diets. Identifying this role for Dab2 could also lead to new pharmaceutical strategies to combat childhood obesity.

Stem Cell First

The Miami Project to Cure Paralysis, a Center of Excellence at the Miller School of Medicine, published findings of its first FDA-approved Phase I clinical trial involving the use of human nerve cells, known as Schwann cells, to repair a damaged spinal cord. “Safety of Autologous Human Schwann Cell Transplantation in Subacute Thoracic Spinal Cord Injury” was published in the February issue of the Journal of Neurotrauma, with Kim D. Anderson, research associate professor in the Department of Neurological Surgery and The Miami Project, as lead author. Six subjects were transplanted for the trial, which was performed at University of Miami/Jackson Memorial Hospital. Participants were followed for one year after the transplantation surgery. Their neurologic and medical status, pain symptoms, and muscle spasticity were evaluated. They will be monitored for five years post-transplantation.

Leading Zika Trial

The Miller School of Medicine is leading one of the nation’s first full-scale Zika vaccine clinical trials of the National Institutes of Health’s experimental DNA-based vaccine. Infectious disease physician Margaret Fischl, B.S. ’72, M.D. ’76, a professor of medicine, director of the HIV/AIDS Clinical Research Unit, and codirector of the Miami Center for AIDS Research, who was also instrumental in testing the first influenza vaccine, will lead the Miami arm of the NIH study. Researchers will recruit individuals from Miami-Dade County, where the nation’s first cases of locally acquired Zika were seen. Participants will be given the vaccine in varying dosages to test safety. The second part of the study, part B, is a double-blind study that aims to determine if the vaccine can effectively prevent disease caused by Zika infection. Residents who weren’t previously infected with Zika from the “Zika zone” neighborhoods where local transmission occurred will be enrolled, with half receiving the vaccine and half receiving a placebo. Initial findings indicate the vaccine is safe and can induce a neutralizing antibody response against Zika virus. The vaccine does not contain infectious material, so it cannot cause Zika infection. The study is expected to be completed by 2019.

Bearish on Brexit?

Indraneel Chakraborty, assistant professor of finance, and Rong Hai, assistant professor of economics, from the School of Business Administration examined data across the European Union with colleagues from Norway and Switzerland to understand the impact of reduced cross-border lending in the wake of the 2008 financial crisis. They found those efforts to reduce risk led to a loss of $90 billion Euro ($97 billion USD) for the continental European economies. According to the study, published in the Journal of Monetary Economics, that kind of pullback in the wake of Britain’s exit from the European Union could also slow gross domestic product growth.

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Miami Project begins FDA-approved Schwann cell trial for spinal cord injury patients

W. Dalton Dietrich, scientific director of The Miami Project to Cure Paralysis Photo by Donna Victor

Schwann Cells Courtesy Miller School of Medicine

With 27 years of promising research came new hope for the new year. In December doctors at The Miami Project to Cure Paralysis performed the first-ever Food and Drug Administration-approved Schwann cell transplantation on a patient with a recent spinal cord injury.

The procedure was performed by University of Miami doctors at Jackson Memorial Hospital five months after the FDA green-lighted its Phase 1 clinical trial designed to evaluate the safety and feasibility of transplanting human Schwann cells, which are found in the peripheral nervous system.

The Miami Project, a Center of Excellence at the Miller School of Medicine, will enroll eight participants with acute thoracic spinal cord injury in the trial, which is part of the Christine E. Lynn Clinical Trials Initiative. They will be followed for a year post-surgery and then monitored for four more years under a separate clinical protocol.

“This trial and these first patients in this trial specifically are extremely important to our mission of curing paralysis,” says neurosurgeon Barth Green, co-founder and chair of The Miami Project, and professor and chair of neurological surgery. “This achievement reaffirms that the tens of millions of dollars and the incalculable work hours were well invested in this first-of-a-kind human Schwann cell project.”

Allan Levi, professor of neurological surgery, orthopaedics, and rehabilitation, and James Guest, associate professor of neurological surgery, conducted the historic procedure several weeks after the patient’s Schwann cells were harvested from tissue obtained from a nerve in one leg and then grown for several weeks in a culturing facility.

W. Dalton Dietrich, scientific director of The Miami Project and professor of neurological surgery, neurology, and cell biology and anatomy, says the trial’s successful completion “will lay the critical foundation for future cell-based therapies to target spinal cord injuries.”

Miami Project: miamiproject.miami.edu/page.aspx?pid=1048

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