Center for Inborn Errors of Immunity


The Center for Inborn Errors of Immunity (CIEI) is working to illuminate the elusive pathogenesis behind genetic disorders of the immune system. Through tireless clinical and translational research, we strive to lay the foundation for a paradigm-shifting approach to the design of both preventative therapies (such as prophylactic drugs, vaccines, and genetic counseling) and novel treatments.

Our member labs are conducting innovative research in the following areas:

Genetics of Immune disorders

Primary immunodeficiencies (PIDs) are a varied group of inborn genetic errors that result in susceptibility to infections, predisposition to malignancy, or disorders of immune overactivation. Currently more than 400 genetic defects have been described. The CIEI seeks to diagnose individuals with known disease and discover new genetic etiologies of disease by using the latest sequencing and analysis technologies. Many of our member labs are working to identify and study these genetic defects. Additionally, CIEI is a part of The Mindich Child Health and Development Institute’s Undiagnosed Disease Program, which is investigating the genetic underpinning of many childhood diseases, including those pertaining to the immune system. Finally, Mount Sinai’s BioMe Biobank collaboration with the Regeneron Genetics Center will allow us and others to identify those individuals who might have silent or late onset conditions.

The average patient with a primary immunodeficiency (PID) waits 9.2 years from symptom onset to diagnosis. The Percha Lab, which is a CIEI member lab, is committed to helping such patients achieve earlier diagnosis and relief from symptoms. Our investigators use machine learning and natural language processing of electronic medical records to identify patients with high risk of PID in order to pave the way to prompt diagnosis.

Detailed Pathophysiology

Understanding the underlying mechanisms of a disease is key to developing successful treatment. To achieve this understanding, each genetic variant must be studied in isolation in order to glean key mechanistic insights. Our CIEI labs use genomics, genetics, molecular biology, cellular biology, immunology, and clinical tools to dissect these phenotypes and develop therapeutics.

Novel Therapeutics, Technologies, and Clinical Trials

The CIEI uses the latest technologies to investigate pathophysiology, but also to unveil existing FDA approved therapies, such as JAK Inhibitor therapy. We are also facilitating the development of novel therapies such as Transient Gene Therapy: Modified mRNA, which is an attractive and novel in vivo gene delivery method that allows high gene expression in variety of organs, including those involved in the immune system. Expression is seen within 20 minutes following delivery and can last from several days to a week. The strength of Modified mRNA as a gene delivery therapy is in its safety, transience, and high expressivity, as recently evidenced by the success of modRNA based SARS-CoV-2 vaccines by two different companies. At the CIEI, we are developing modRNA tools to successfully modify immune state and cure disease.

Immune Monitoring

A key component to understanding inborn errors of immunity is the detailed mapping and functional assessment of the immune system. The CIEI is thus working closely with the Human Immune Monitoring Center (HIMC), which leverages cutting-edge technologies and deep immunological and technical expertise to provide comprehensive immune monitoring for clinical and translational studies.