To develop new therapies, we need to identify actionable molecular targets of disease. These are the genes, cells, or molecules driving disease that can be ‘drugged’ to return a tissue to homeostasis. At the Icahn Genomics Institute (IGI) we are uncovering novel disease targets through a multiscale approach that includes comprehensive analysis of patient tissues at the gene, transcript, cell, and organ level, employing functional genomics to establish causal factors of disease, and applying data science and artificial intelligence (AI) to identify pivotal nodes in convoluted biological networks.
Through extensive analysis of patient genetics, gene expression, and single cell data we can identify variations between healthy and disease states and use these insights to improve patient treatment. Since the data is highly complex, the IGI is developing and employing advanced computational approaches, including AI and machine learning, to decrypt the disease drivers, as well as uncover novel biomarkers to inform precision treatments. This has already started to transform patient care. Using advanced molecular techniques, scientists in the IGI have been able to resolve the disease etiology of different patients with undiagnosed conditions. In one case, it was determined that a patient’s immune disorder was caused by deficiencies in USP18, a negative regulator of JAK/STAT signaling, and subsequently, they were able to repurpose a JAK inhibitor and effectively treat the patient’s life-threatening condition.
Functional genomics, using CRISPR screens, is also being used to identify novel drug targets. Scientists at the IGI have invented a powerful new technology for functional genomics, which enables, for the first time, CRISPR screens to be resolved in situ with spatial resolution. This greatly expands target discovery by enabling the disease-causing role of genes operating extrinsically, such as cytokines, to be determined and represents a new frontier for identifying drug targets in cancer and other diseases by functional genomics.
As our knowledge of diseases mechanisms increases, we will find and develop new therapeutics to many diseases that have previously defied treatment.
Our Team
Panagiotis Roussos, MD, MS, PhD