Stephen Persaud, MD, PhD

Division

• Laboratory & Genomic Medicine

Additional Titles

• Clinical Pathology-Physician Scientist Training Program

Board Certifications

• Medical Licensure, Missouri Board for the Healing Arts, 2018-present
• Diplomate, American Board of Pathology (Clinical Pathology), 2018-2028

Recognition

• American Society of Hematology Fellow-to-Faculty Scholar Award (2023)
• NCI Research Supplement to Promote Diversity in Health-Related Research (with John DiPersio) (2022)
• Developmental Research Program Award, Washington University SPORE in Leukemia (2022)
• Career Enhancement Program Award, Washington University SPORE in Leukemia (2020)
• New Investigator Award, American Society for Transplantation and Cellular Therapy (2020)
• Trainee Abstract Achievement Award, American Society of Hematology (2019)
• Paul Calabresi K12 Career Development Award in Clinical Oncology (relinquished to accept SPORE CEP) (2019)
• Outstanding Grand Rounds Presentation Award, Division of Laboratory and Genomic Medicine (2016)
• American Association of Immunologists Travel Award (2013)
• NIH/NHLBI K08 Career Development Award (2024)

Clinical Interests

• Hematopoietic stem cell transplantation
• Gene and cellular immunotherapies
• Sickle cell disease
• Acute myeloid leukemia

Research Interests

Hematopoietic stem cell transplantation (HSCT) holds the potential for cure of a variety of malignant and non-malignant hematologic disorders. However, the severe acute and chronic toxicities imposed by the chemotherapy- and irradiation-based conditioning regimens used to prepare recipients for transplant may preclude them from accessing the lifesaving benefits of HSCT. My research seeks to address this urgent and unmet need by developing minimally toxic, immunotherapeutic conditioning strategies which enable the therapeutic benefits of HSCT with minimal injury to the recipient.

During my postdoctoral training in Dr. John DiPersio’s lab, I discovered a novel allogeneic HSCT conditioning strategy combining Janus kinase 1/2 inhibitors with CD45- or CD117-targeted antibody-drug conjugates (ADC), which enabled stable engraftment between fully MHC-mismatched mice with >99% myeloid lineage donor chimerism. Notably, compared to conditioning with irradiation,  ADC-based conditioning in murine models did not promote graft-versus-host disease. Several projects stemming from this work seek to optimize antibody-based conditioning regimens to better achieve the therapeutic goals of transplant in specific disease settings. For example, we 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 are developing 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.

Selected Publications

Yelamali AR, Chendamarai E, Ritchey JK, Rettig MP, DiPersio JF, Persaud SP. Streptavidin-drug conjugates streamline optimization of antibody-based conditioning for hematopoietic stem cell transplantation. BioRxiv [Preprint]. 2024 Feb. doi:10.1101/2024.02.12.579199. PMCID: PMC10888937

Persaud SP, Yelamali AR, Ritchey JK, DiPersio JF. Conditioning with anti-CD47 and anti-CD117 plus JAK inhibition enables toxic payload-free allogeneic transplantation. Blood Adv. 2024 Sep 10; 8(17). PubMed PMID: 38968137; PMCID not yet assigned.

Persaud SP, Ritchey JK, Kim S, Lim S, Ruminski PG, Cooper ML, Rettig MP, Choi J, DiPersio JF. Antibody-drug conjugates plus Janus kinase inhibitors enable MHC-mismatched allogeneic hematopoietic stem cell transplantation. J Clin Invest. 2021 Dec 15;131(24):e145501. PMID: 34730109

Johnson DK, Magoffin W, Myers SJ, Finnell JG, Hancock JC, Orton TS, Persaud SP, Christensen KA, Weber KS. CD4 Inhibits Helper T Cell Activation at Lower Affinity Threshold for Full-Length T Cell Receptors Than Single Chain Signaling Constructs. Front Immunol. 2021 Jan 19;11:561889. PMID: 33542711

Persaud SP, Lawton T, Burnham CD, Anderson NW. Comparison of urine antigen assays for the diagnosis of Histoplasma capsulatum infection. J Appl Lab Med. 2019 Nov;4(3):370-382. PubMed PMID: 31659074. https://academic.oup.com/jalm/articleabstract/4/3/370/5636918?redirectedFrom=fulltext

Persaud SP, Duffy B, Phelan D, Mohanakumar T, Delos Santos R, Gaut JP, Liu C. Accelerated humoral renal allograft rejection due to HLA-C14 mediated allosensitization to HLA-Bw6. Hum Immunol 2017 Nov; 78: 692-698. PMID: 29024716. https://www.sciencedirect.com/science/article/abs/pii/S0198885917305086?via%3Dihub

Jackups R Jr., Szymanski JJ, Persaud SP. Clinical decision support for hematology laboratory test utilization. Int J Lab Hematol 2017 May; 39(Supplement 1): 128-35. PMID: 28447421. https://onlinelibrary.wiley.com/doi/full/10.1111/ijlh.12679

Persaud SP, Hassan A, Hassan A, Hassan T. Severe Cytomegalovirus Gastritis During Natalizumab-Mediated Immunosuppression. ACG Case Rep J 2017 Mar; 4: e43. PMID: 28331881. https://journals.lww.com/acgcr/Fulltext/2017/04000/Severe_Cytomegalovirus_Gastritis_During.43.aspx

Hong J, Persaud SP, Horvath S, Allen PM, Evavold BD, Zhu C. Force-Regulated In Situ TCR-Peptide-Bound MHC Class II Kinetics Determine Functions of CD4+ T Cells. J Immunol 2015 Oct; 195(8):3557-64. PMID: 26336148. https://www.jimmunol.org/content/195/8/3557.long

Chou C, Pinto AK, Curtis JD, Persaud SP, Cella M, Lin CC, Edelson BT, Allen PM, Colonna M, Pearce EL, Diamond MS, Egawa T. c-Myc-induced transcription factor AP4 is required for host protection mediated by CD8+ T cells. Nat Immunology. 2014 Sep; 15(9): 884-893. PMID: 25029552. https://www.nature.com/articles/ni.2943

KC W, Satpathy AT, Rapaport AS, Briseño CG, Wu X, Albring JC, Russler-Germain EV, Kretzer NM, Durai V, Persaud SP, Edelson BT, Loschko J, Cella M, Allen PM, Nussenzweig MC, Colonna M, Sleckman BP, Murphy TL, Murphy KM. L-Myc expression by dendritic cells is required for optimal T-cell priming. Nature. 2014 Mar; 507(7491): 243-247. PMID: 24509714. https://www.nature.com/articles/nature12967

Persaud SP, Parker CR, Lo WL, Weber KS, Allen PM. Intrinsic CD4+ T cell sensitivity and response to a pathogen are set and sustained by avidity for thymic and peripheral complexes of self-peptide and MHC. Nat Immunology. 2014 Mar; 15(3): 266-274. PMID: 24487322. https://www.nature.com/articles/ni.2822

Weber KS, Li QJ, Persaud SP, Campbell JD, Davis MM, Allen PM. Distinct CD4+ helper T cells involved in primary and secondary responses to infection. Proc Nat Acad Sci USA. 2012 Jun; 109(24): 9511-9516. PMID: 22645349. https://www.pnas.org/content/109/24/9511.long