Department of Microbial Pathogenesis posts displayed by tag

Feng

Research Professor Wins Entrepreneurial Award

In 2007, Hanping Feng, PhD, then a research assistant professor at Tufts University Cummings School of Veterinary Medicine, decided to transition from basic research to translational research. “I wanted to do something that had a direct impact on human health,” he says.

A decade later, he hasn’t changed his mind. Now a professor in the Department of Microbial Pathogenesis at the University of Maryland School of Dentistry (UMSOD), he is a co-founder of Fzata, Inc., an antibody technology startup company, which in June was named “Best Life Sciences Company” at the Maryland Incubator Company of the Year awards ceremony. Now in its 16th year, the honor is presented annually by a committee of regional leaders and early-stage investors in recognition of promising fledgling technology companies in Maryland.

Feng’s research is focused on the development of novel diagnostics, vaccines, and antibody-based immunotherapies for Clostridium difficile infection (CDI). More than 29,000 deaths in the United States are caused annually by antibiotic-resistant C. difficile; globally the infection is considered an urgent public health threat.

“It’s a huge problem particularly in westernized countries,” says Feng. “It develops frequently in hospitals where antibiotics are administered. Patients expose spores and then develop an infection. The problem is that currently there’s no prevention nor good treatment strategy.”

Feng’s team has developed a highly innovative and multi-specific antitoxin antibody that has been shown to be effective in neutralizing both clostridial toxins and blocking the disease. Based on this research, Feng and FZata team is developing two candidate drug products: an intravenous, fully humanized, tetra-specific, antibody product (FZ001) designed to treat ongoing infection and to prevent recurrence, and an oral, probiotic, yeast product (FZ002) that secretes the antitoxin at the site of infection.

Both drug candidates have been evaluated in animal models of human infection and reveal superior efficacy against the infection than competitors.

In 2015, Feng and co-founder Zhiyong Yang, PhD, a former research scientist, formed FZata to fast track drug candidates by creating a viable pathway toward clinical trials, and ultimately commercial production. “There’s a big gap between University bench work and clinical study for biologics,” Feng says. “The process is expensive and the large pharmaceutical companies don’t want to invest at an early stage because it’s risky.”

The early success of Fzata gives Feng hope that his model can be successful. “We’ve been able to get support because it’s innovative, and it’s centered on a major public health issue.”

Since 2011, when he came to UMSOD from Tufts University, Feng’s research has been supported by 14 grants or contracts totaling $15 million. Most recently, FZata received a $5.6 million National Institutes of Health grant to enable development of lead therapeutics against CDI.

  
Scott Hesel Bulletin Board, Contests, People, Research, TechnologyJuly 24, 20170 comments
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Krantz and Das

Dentistry-led Anthrax Study in Prestiguous Journal

The University of Maryland School of Dentistry’s research team achieved an unprecedented breakthrough with the acceptance of a recent manuscript into the publication Proceedings of the National Academy of Sciences of the United States of America (PNAS). ‌

This manuscript, “Peptide and Proton Driven Allosteric Clamps Catalyze Anthrax Toxin Translocation across Membranes,” is the first such paper to be accepted into this prestigious journal in the history of UMSOD. The paper was co-authored by Bryan Krantz, PhD, associate professor, and Debasis Das, PhD, a postdoctorate fellow, both in the Department of Microbial Pathogenesis (pictured).

The primary focus of the research centered on the components of the anthrax toxin protein. The anthrax toxin contains three components. One component forms a channel – or pore – in the cell membrane. The other component goes through that pore into the cell. Once that second component (referred to as the ‘substrate’) makes it into the cell, it carries out reactions that disrupts the cell’s functions.

Working from a foundation provided by researchers at the University of California, Berkeley, Das and Krantz discovered evidence that this translocation mechanism is under allosteric control. Allosteric regulation is a process wherein proteins transmit the effect of binding at one site to another, often at a location other than the enzyme’s active site. In the case of the Anthrax toxin, when the pore part of the protein binds, the substrate part that is disrupting the cell binds tighter as well, despite being at a different location.

“This tells us how the anthrax pore functions,” said Krantz, “there are huge implications because this is an entirely new way of thinking about the translocation mechanism.”

Previously, there had been no documented evidence showing that the mechanism of translation carried out by the pore protein was under allosteric control. The importance of this discovery is a major reason why the manuscript was accepted into PNAS, according to Krantz.

“This is a landmark discovery that may find its way into textbooks,” said Patrik Bavoil, PhD, professor and chair in the Department of Microbial Pathogenesis, “this is a model for how all proteins, not just the anthrax toxin, translocate across membranes.”

This accomplishment caps off a successful two months for UMSOD research efforts. On May 29, Vineet Dhar, PhD, in the Department of Pediatrics won the Paul P. Taylor award from the American Academy of Pediatric Dentistry (AAPD) for his paper evaluating the evidence of effectiveness of interventions for Early Childhood Carries (ECC).

For Krantz and Das, the next steps will include additional research into their discovery through grants awarded by the National Institutes of Health.

  
Scott Hesel ResearchJuly 22, 20160 comments
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