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Research at Mass General
Cammie Lesser, MD, PhD, is hoping to transform a function evolved by harmful bacteria into a method for delivering treatments to patients.
Cammie Lesser, MD, PhD, has always been fascinated by the way bacterial pathogens manipulate cells inside the human body. She likens the push and pull between bacterial aggression and human response as a struggle similar to warfare on the microbiological level.
Dr. Lesser, a researcher and clinician in the Department of Infectious Disease, is one of the six recently named MGH Research Scholars in the class of 2016.
She plans to use her scholar funding ($500,000 distributed over five years) to pursue a new strategy in the battle between bacteria and humans—taking a process that originally evolved to help harmful bacteria spread and reengineering it to provide a helpful function instead.
The work could one day result in low-cost, highly-specific methods for treating infectious diseases, autoimmune disorders and even cancer.
Cammie Lesser, MD, PhD (right) discusses bacterial strains with lab member Catherine Ma.
In a recent interview, Lesser explained that certain types of harmful bacteria strains have evolved mechanisms called nanomachines that they use to transfer proteins directly into human cells.
These proteins are designed to disrupt cell function and impair the body’s immune response, thus making it easier for the harmful bacteria to spread.
In the case of Shigella bacteria, the harmful proteins act to disrupt normal cell function in the intestine, creating a niche for the bacteria to live in the cells of the intestinal wall.
As the bacteria replicate, they release toxins into the intestine that in turn cause inflammation and diarrhea, which helps the bacteria spread to new hosts.
In recent years, Lesser and other researchers have identified the different types of harmful proteins that are transferred by these nanomachines, and have figured out the chemical signatures that the nanomachines use to identify which proteins to transfer.
In the process of studying the science behind these mechanisms, Lesser and her team came up with an intriguing proposition: Could they reengineer these nanomachines to deliver beneficial proteins instead?
The idea originated from Lesser’s work as an infectious disease doctor at Mass General. She explained that many of the patients she sees are suffering from conditions such as inflammatory bowel disease (IBD) or cancer and have developed infections as a result of their treatments.
For example, patients with IBD are often treated with immune suppressants, which help to calm autoimmune flare-ups in the gut. But these medications also suppress immune response throughout the body, leaving the patient more susceptible to infections and infection-related conditions such as disseminated tuberculosis and brain abscesses.
By equipping beneficial bacteria with proteins that could go directly into the gut and calm the autoimmune response at the source, Lesser hopes to provide patients with relief while leaving the rest of immune system intact.
Lesser and her team have already been successful in transferring the nanomachine function into beneficial bacteria and in getting those bacteria to distribute beneficial proteins. They are now working to improve the viability of these modified strains before testing the process in laboratory models.
While it may take some time before the treatment is ready to be tested in humans, Lesser is confident that the approach has promise, and is grateful to have Scholar funding to support this preliminary work.
“We can show that we can make the bacteria strains; we can show the strains can secrete what we want. Getting to the next step is a leap of faith,” she acknowledges. “But we think it’s a worthwhile leap of faith.”
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