Although most people associate salmonella with a bad case of food poisoning, a team of Duke scientists have shown that the bacteria could potentially be used to treat cancer.
Led by Ravi Bellamkonda, Vinik Dean of the Pratt School of Engineering, the researchers adopted a strain of Salmonella typhimurium and made several genetic modifications to the bacterial DNA. These changes enabled the bacteria to produce tumor suppressor proteins called p53 and Azurin, which were able to destroy glioblastoma tumors in the brains of nearly 20 percent of the mice tested.
“One of the challenges of glioblastoma is its tendency to infiltrate the rest of the brain, blurring the boundaries of where tumor is and where normal brain is,” Bellamkonda said.
The metastasis, or invasive spread, of the cancer prevents doctors from surgically removing the tumor and requires a more creative solution to the problem. To accomplish this, the team turned to a strain of salmonella developed in the laboratory of David Bermudes, associate professor of biology at California State University at Northridge.
“They removed this toxic protein that’s expressed on the bacterial cells,” said Johnathan Lyon, a study co-author and Ph.D. candidate in Bellamkonda’s lab. “[The modified bacteria] are essentially just like the healthy bacteria in your body. They don’t really warrant an immune response.”
Lyon noted that the bacteria are altered so that they are unable to produce a key nutrient called purine. Tumors are purine-rich, however, causing the bacteria to seek out the tumors for survival.
The Duke researchers also made several additional tweaks of their own to the bacteria’s genome.
“We’ve made it so that once it reaches the tumor, it triggers a manufacturing of drug combination p53 and Azurin,” Lyon said.
The protein p53 initiates the process of cell death when released inside a cell. Lyon explained that the bacteria are able to penetrate the cell membrane and deliver their payload of p53, leading to the destruction of the tumor cell.
Bellamkonda added that the researchers also built in a safeguard to ensure that the bacteria would not release p53 when taken in by a healthy cell.
“Only in regions where the oxygen is low would these proteins be turned on,” Bellamkonda said. “For the most part, the oxygen concentration tends to be pretty high, except in the regions of cancer where the tumors are growing so fast.”...
Ravi Bellamkonda, a renowned biomedical engineer who has led one of the top-ranked departments in the country, will be the new Vinik Dean of the Pratt School of Engineering at Duke University, President Richard H. Brodhead and Provost Sally Kornbluth announced Tuesday.
Bellamkonda is the Wallace H. Coulter Professor and chair of the Wallace H. Coulter Department of Biomedical Engineering at Georgia Institute of Technology and Emory University, a unique collaboration between the two Atlanta institutions at which he holds a joint faculty appointment. His Duke appointment, which is effective Aug. 1, comes after an international search chaired by Jeff Glass, professor of electrical and computer engineering. Bellamkonda succeeds Tom Katsouleas, who was named provost of the University of Virginia in 2015.
“The ascent of the Pratt School of Engineering has been an important development in Duke’s ability to generate knowledge in service to society, as engineering plays a critical role in addressing virtually every contemporary challenge,” Brodhead said. “Ravi Bellamkonda has a record of outstanding personal accomplishment and visionary leadership. Working with Pratt faculty and students, he will continue Duke Engineering’s remarkable trajectory and will be an excellent partner across the university.”...
Newswise — The tumor monorail project, a collaboration between the Georgia Institute of Technology, Children’s Healthcare of Atlanta and Emory University, will receive a $6.5 million grant from The Marcus Foundation. The project involves the design and testing of a novel device for more efficient treatment of brain tumors.
“Support from The Marcus Foundation will enable us to accelerate the development of a novel tumor monorail device to treat brain tumors in patients,” said Ravi Bellamkonda, Wallace H. Coulter Chair in Biomedical Engineering and lead investigator of this project. “Research labs such as ours are set up to achieve scientific and engineering breakthroughs, but for these breakthroughs to reach patients, we need to follow good manufacturing practices, rigorous safety and quality testing, adhere to FDA guidelines for obtaining regulatory approvals, and design appropriate clinical trials. All of these processes are going to be greatly enhanced and accelerated with this critical and visionary Marcus Foundation support.”
Funding from The Marcus Foundation will enable researchers to move this technology into clinical trials and ultimately to people who are facing these medical challenges. The grant will also enable device design and prototyping, development of an FDA-compliant manufacturing process and FDA approvals for a clinical Investigational New Drug (IND) study to be conducted in Atlanta....
The Georgia Institute of Technology and Emory University have selected Ravi V. Bellamkonda, PhD, a prominent biomedical scientist and engineer, to chair their joint department of biomedical engineering. He will begin as chair of the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University in July.
Bellamkonda, who has built a distinguished career in the health and engineering fields, is currently the Carol Ann and David D. Flanagan Chair in Biomedical Engineering and a Georgia Research Alliance Distinguished Cancer Scientist. He currently serves as the Georgia Tech associate vice president for research, and he is the new president-elect for the American Institute for Medical and Biological Engineering (AIMBE)....
Children’s Healthcare of Atlanta and the Georgia Institute of Technology announce new technique that increases precision in brain tumor removal
In an article published this week in the journal Drug Delivery and Translational Medicine, researchers from Children’s Healthcare of Atlanta and the Georgia Institute of Technology have reported the development of a technique that assists in identifying tumors from normal brain tissue during surgery by staining tumor cells blue. This key finding, developed by a team led by Dr. Barun Brahma, M.D., Children’s neurosurgeon and biomedical engineer, and Prof. Ravi Bellamkonda, the Carol Ann and David D. Flanagan Chair in Biomedical Engineering at the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, could be a critical technique used in hospitals lacking sophisticated equipment like an MRI, which guides in tumor removal, in preserving the maximum amount of normal tissue and brain function during surgery....
Treating invasive brain tumors with a combination of chemotherapy and radiation has improved clinical outcomes, but few patients survive longer than two years after diagnosis. The effectiveness of the treatment is limited by the tumor’s aggressive invasion of healthy brain tissue, which restricts chemotherapy access to the cancer cells and complicates surgical removal of the tumor.
To address this challenge, researchers from the Georgia Institute of Technology and Emory University have designed a new treatment approach that appears to halt the spread of cancer cells into normal brain tissue in animal models. The researchers treated animals possessing an invasive tumor with a vesicle carrying a molecule called imipramine blue, followed by conventional doxorubicin chemotherapy. The tumors ceased their invasion of healthy tissue and the animals survived longer than animals treated with chemotherapy alone.
“Our results show that imipramine blue stops tumor invasion into healthy tissue and enhances the efficacy of chemotherapy, which suggests that chemotherapy may be more effective when the target is stationary,” said Ravi Bellamkonda, a professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. “These results reveal a new strategy for treating brain cancer that could improve clinical outcomes.”...
A new nerve-cell-support design could give amputees better control over prosthetic limbs.
To design prosthetic limbs with motor control and a sense of touch, researchers have been looking at ways to connect electrodes to nerve endings on the arm or leg and then to translate signals from those nerves into electrical instructions for moving the mechanical limb. However, severed nerve cells on an amputated limb can only grow if a structure is present to support them—much the way a trellis supports a growing vine. And they are notoriously fussy about the shape and size of that structure.
“Cells are like people: they like furniture to sit in that’s just the right size,” says David Martin, a biomedical engineer at the University of Delaware. “They’re looking for a channel that’s got the ‘Goldilocks’-length scale to it—how far apart the ridges are, how tall they are, how [wide] they are.”
Ravi Bellamkonda’s lab at Georgia Tech has designed a tubular support scaffold with tiny channels that fit snugly around bundles of nerve cells. The group recently tested the structure with dorsal root ganglion cells and presented the results at the Society for Biomaterials conference earlier this month....
$1M grant awarded to Coulter Department professor Ravi Bellamkonda
The Georgia Institute of Technology has received a EUREKA grant from the National Institutes of Health (NIH) to design a new way to treat invasive brain tumors by capturing the migrating cells that spread the disease. The EUREKA — Exceptional, Unconventional Research Enabling Knowledge Acceleration — program helps scientists test new, unconventional ideas or tackle major methodological or technical challenges.
The research team plans to develop a system that will excavate brain tumor cells by directing them away from their location in the interior of the brain to a more external location where they can be removed or killed. Nanofiber-based polymer thin films coated with biochemical cues will be aligned in the brain to provide a corridor for tumor cells to follow to a gel-based ‘sink’ where they will be captured and safely removed or encouraged to die through chemical signaling.
“We believe this is the first attempt to exploit the invasive, migrating properties of brain tumors by engineering a path for the tumors to move away from the primary site to a location where treatment can occur,” said lead investigator Ravi Bellamkonda, a professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University....
Three-year appointment allows continuation of research agenda
Ravi Bellamkonda, a professor in the Wallace H. Coulter Department of Biomedical Engineering, has been named an associate vice president within the Office of the Executive Vice President for Research (EVPR). The three-year appointment, which begins on August 1, enables Bellamkonda to divide his time evenly between his own research and the administrative responsibilities of this new position....