The focus of our program is currently on the identification, diagnosis, and treatment of various primary immunodeficiencies especially as related to the chemotactic cytokine (chemokine) system which directs the migration, adhesion, activation, and function of leukocytes. We focus on WHIMS (Warts, Hypogammaglobulinemia, Infections, and Myelokathexis Syndrome) which is due to autosomal dominant gain-of-function mutations in the CXCL12 chemokine receptor and HIV coreceptor known as CXCR4. We are repurposing a small molecule CXCR4 antagonist to treat this disorder and working on gene therapy to cure the disease as we have found that hematopoietic stem cells that lack one copy of CXCR4 have a selective bone marrow engraftment advantage. We are also working on a metabolic cause of severe congenital neutropenia and neutrophil dysfunction known as G6PC3 deficiency and attempting to repurpose empagliflozin to reduce the impact of a toxic metabolite of a dietary sugar that accumulates in leukocytes in this autosomal recessive immunodeficiency. Finally, in collaboration with Gigi Notarangelo’s group in NIAID, we recently discovered a novel immunodeficiency syndrome known as SASH3 immunodeficiency and are working on understanding the mechanism of the susceptibility to infectious diseases and autoimmunity that results from this X-linked recessive disorder.