Yale University is one of three partners that will form a new biomedical research hub announced by the Chan Zuckerberg Initiative (CZI). The mission of CZ Biohub New York, to be located in New York City, will be to bioengineer immune cells to detect the earliest stages of diseases—potentially allowing clinicians to intervene before they become symptomatic and detectable using current approaches. Yale’s team will be led by John Tsang, PhD, professor of immunobiology and of biomedical engineering at Yale School of Medicine and director of the Yale Center for Systems and Engineering Immunology (CSEI). The Biohub will be a collaboration between Columbia University, The Rockefeller University, and Yale. Researchers across the three institutions will work together with new technologies to bioengineer immune cells —with the ultimate goal of creating disease-specific “cellular endoscopes” that can detect, monitor, and resolve early stages of disease in human tissues and organs. “Blood has been a key window for monitoring the status of the human immune system and health, but early signs of disease often reside in inaccessible organs and tissues,” said Tsang, who has been a leader in conceiving and developing the vision of learning from and engineering immune cells to detect early signals of disease and restore health in human tissues. “Circulating immune cells offer a fabulous platform to develop non-invasive, organ-homing sensors and maintainers of health.” “We’re thrilled to launch the New York Biohub, which will focus on harnessing our immune system to detect, prevent, and ultimately treat diseases before they advance,” said CZI co-founder and co-CEO Priscilla Chan. “Solving ambitious challenges, like identifying diseases earlier when our options for treatment are far better, underpins our work across the Biohub Network, and we’re excited to continue to scale this collaborative research model with the New York Biohub.” Immune cells are a key tool in disease prevention Lab tests and imaging scans can help doctors make some early diagnoses, but developing tools that can detect abnormalities before diseases take hold offers the potential to dramatically improve medical care. Immune cells are ideally suited to meet this challenge, as they are the only cells in our body that come in contact with virtually all of our tissues. They constantly roam the body by way of the blood and lymphatic system, which can make them effective in helping to monitor and maintain the health of our organs. CZ Biohub NY will use single-cell biology tools, cutting-edge experimental technologies, synthetic biology, machine learning, and artificial intelligence (AI) to unlock the spatial and temporal control of immune cells, including utilizing the vast information stored in the “molecular memory” of these cells, with the goal of bioengineering new functions into immune cells to continuously monitor and manage organ and tissue health. Over the past decade, cancer immunotherapies—treatments in which immune cells are engineered to specifically attack tumors—have seen great success and have become mainstream therapies for certain forms of cancer. But there has been considerably less scientific attention on the medical potential of the sensing and “molecular recording” capabilities inherent to immune cells that come in contact with diseased cells. CZ Biohub NY aims to refine and amplify this ability to detect and decode subtle signs of early-stage disease that can elude conventional testing, as well as to deliver treatment directly upon detection. Bioengineering immune cells to treat cancer, neurodegenerative disease, and beyond Andrea Califano, PhD, Clyde and Helen Wu Professor of Chemical and Systems Biology at Columbia University, will lead CZ Biohub NY, which will first focus on learning more about the molecular memory and states of immune cells when they sense signals secreted by diseased cells and organs. This will help predict early signs of disease that are tissue-specific. Building on this, researchers will work to understand the mechanisms of immune cell trafficking to further direct cells to desired organs on-demand and to sense novel disease signals they are not yet built to detect. This will help CZ Biohub NY to bioengineer immune cells that can travel to specific organs, sense any potential abnormalities, and then record information in their molecular state for easy detection from a simple blood draw—or by using non-invasive engineered devices—for further interpretation by scientists and eventually physicians. What we need is to develop a better scientific understanding of those processes, and invent new technologies to precisely program immune cells to go to specific tissues, detect and report back on early signals of disease, and ultimately, act to restore health.John Tsang, PhD “Immune cells have evolved sophisticated machineries to monitor and resolve early deviations from health in human organs. They do that routinely without us even knowing, for example, to stop autoimmune and cancer cells from growing,” Tsang added. “What we need is to develop a better scientific understanding of those processes, and invent new technologies to precisely program immune cells to go to specific tissues, detect and report back on early signals of disease, and ultimately, act to restore health.” "The grand scientific question that these scientists are going to go after is around cellular engineering — to engineer immune cells to detect specific diseases and then eventually encode their molecular make-up, so that scientists can use it as a diagnostic and eventually, they can engineer cells to go to a site of a disease and help treat it," said CZI co-founder and co-CEO Mark Zuckerberg. "The ultimate goal is to not go after a specific disease – it’s to create a new tool or platform that all scientists can use to study and make more specific advances." CZ Biohub New York will initially apply these novel, technology-driven approaches to hard-to-detect cancers such as ovarian and pancreatic cancers; neurodegenerative diseases, including Parkinson’s and Alzheimer’s, as well as aging and autoimmunity. The next step is further training immune cells to make targeted repairs, or promote inflammation at a tumor site to activate a robust immune response. CZ Biohub New York is the fourth research institute in the Chan Zuckerberg Biohub Network, a groundbreaking collaborative model for scientific research. The network includes the first CZ Biohub, in San Francisco, a second in Chicago, and the Chan Zuckerberg Institute for Advanced Biological Imaging in Redwood City, California.