Keystone Symposia recently hosted an ePanel featuring the 2024 Michelson Philanthropies & Science Prize for Immunology recipients.
The event, titled “Michelson Philanthropies & Science Prize for Immunology Awards: Breakthrough Discoveries in Human Immunology,” welcomed Grand Prize recipient Bingxu Liu and finalists Carla Nowosad and Gabriele Casirati. During the panel, the three winning investigators presented their groundbreaking research in human immunology and responded to viewers’ questions.
The ePanel included Dr. Bingxu Liu’s presentation, ‘Protons are the new first responders to danger: Human STING’s newfound function as a channel expands our understanding of immunity.’ Dr. Liu, a postdoc at the Institute for Protein Design at the University of Washington, was awarded $30,000 for his research on improving the human immune system through protein engineering.
Dr. Liu’s work focuses on Stimulator of Interferon Genes (STING), an innate immune sensor that coordinates several different kinds of immune responses. Liu discovered that a hollow channel runs through the STING protein’s center. By blocking this channel with a drug, Liu found that STING not only directs other molecules to fight invaders but also participates in the fight directly.
This is due to a structure found inside cells called a Golgi body. When STING recognizes an infected cell, it moves into the membrane of a Golgi body, allowing hydrogen ions to leak out of its channel. The leak triggers the cell to either eat the Golgi or to kill itself instead.
Knowing that STING can help kill cells on its own opens possibilities that will allow researchers to fine-tune different mechanisms to battle various pathogens or diseases. For example, drug or cell therapies could activate it to kill cancerous cells or block its pore in immune cells so they stay alive to fight off infections.
Finalist Dr. Gabriele Casirati, a postdoctoral fellow at Boston Children’s Hospital and Dana Farber Cancer Institute, started the event with his presentation ‘Stem cells in disguise: How epitope editing can empower targeted cancer immunotherapies.’
Dr. Casirati’s work concerns the use of epitope editing, a form of targeted immunotherapy, to treat acute myeloid leukemia (AML). Despite advances in AML treatment, survival rates remain low, with up to 50% of patients relapsing after stem cell transplants due to lingering cancerous cells. This means oncologists must devise a second treatment to kill the last of these cells.
CAR-T cells and antibody therapies are effective forms of this second treatment. They can recognize specific proteins, known as epitopes, that sit on the surface of cancerous cells, allowing them to kill them without harming healthy cells. However, with AML, the epitopes on the cancerous cells are the same as those on the surface of the donor’s healthy bone marrow stem cells. The lack of AML-specific targets means the treatment could kill the healthy cells a patient depends on.
Through “epitope editing,” Casirati can alter specific amino acids on cell surface markers to avoid targeting healthy cells. His research aims to develop safer immunotherapies for AML, minimizing toxicity while treating the disease.
Dr. Carla Nowosad, finalist and assistant professor in the Department of Pathology at New York University’s Langone Grossman School of Medicine, presented, ‘Who goes there? How B cells assess risk in the intestine.’
Dr. Nowosad investigates how immune cells – B cells – in the intestine maintain a balance between the body and its bacteria, distinguishing between “friend and foe” to help us maintain a healthy immune system. B Cells produce antibodies. In the intestine, antibodies help manage the microbiome, and shifts in the composition of the microbiome can impact the onset and progression of many diseases, including inflammatory bowel disease, obesity, cancer, and depression.
B cells are born in germinal centers (GCs), where they learn to make antibodies that will attack bacteria. However, in the gut, these antibodies are exposed to bacteria that they don’t attack.
Nowosad’s research highlights the intricate relationship between B cells and the microbiome, showing how gut bacteria shape B cell selection and antibody responses. Further exploration into these relationships could have a profound impact on improving cancer immunotherapies or antibiotic treatment, which often disturb the delicate balance of microbiomes.
The Michelson Philanthropies & Science Prize was a three-year collaboration between the Michelson Medical Research Foundation and Science supporting young investigators doing transformative research in human immunology, based on work completed in the past three years.
Watch the full recording of the ePanel.
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