Stephen P. Persaud

Background

About Stephen P. Persaud

I am a physician-scientist dedicated to the advancement of basic science for the betterment of human health. My overarching scientific interests are focused on understanding how the immune system recognizes self from non-self and how this critical distinction is manifest in disease. As a graduate student studying with Dr. Paul Allen, I studied how weak interactions between the T cell receptor and self-peptide bound MHC molecules impacted the fate and function of CD4+ T cells, particularly their response to infection. As a postdoctoral fellow and junior faculty member working with Dr. John DiPersio, I discovered a novel immunotherapeutic approach to allogeneic hematopoietic stem cell transplantation (HSCT) conditioning with JAK1/2 inhibitors and stem cell niche-ablating antibody-drug conjugates; this combination enabled transplantation across immunological barriers without the toxicities of conventional chemotherapy- or irradiation-based conditioning regimens. My research and clinical experiences over the last eighteen years-encompassing immunology, cancer biology and stem cell biology-have prepared me well to launch an independent research laboratory dedicated to improving the safety and efficacy of HSCT as definitive therapy for malignant and non-malignant blood diseases. I am currently developing several projects stemming from my work in the DiPersio lab, which seek to optimize antibody-based conditioning regimens to better achieve the therapeutic goals of transplant in specific disease settings. These projects will form the foundation for the work done in my independent research laboratory. First, we have developed highly potent, fully myeloablative ADCs designed for HSCT conditioning in the context of acute myeloid leukemia, for which induction of full donor chimerism and maximal antileukemia benefit enabled by the conditioning regimen affords protection from relapse. For non-malignant diseases like sickle cell disease, in which antileukemia benefit is not needed and mixed chimerism is sufficient for cure, we have developed toxic payload-free regimens able to achieve cure with as few toxicities as possible when used in conjunction with either allogeneic HSCT or autologous gene therapy.