When the Rules Don't Fit: How Clinical Outliers Point the Way to Cure Hemoglobin Disorders.
Swee Lay Thein, B.S., F.R.C.P., F.R.C.Path., D.Sc., FMedSci
NIH Distinguished Clinical Investigator
NHLBI/NIH
Dr. Swee Lay Thein is Senior Investigator and Chief of the Sickle Cell Branch at the National Heart, Lung, and Blood Institute. An internationally recognized hematologist, she previously served as Professor of Molecular Hematology and Clinical Director of the Red Cell Centre at King’s College London. Her research focuses on sickle cell disease, thalassemia, and other inherited red blood cell disorders. Dr. Thein has authored more than 400 scientific publications and is a Fellow of the U.K. Academy of Medical Sciences. She has held leadership roles with the European Hematology Association and organized the international Sickle Cell in Focus conference.
Summary
Through two clinical vignettes, this lecture explores how observations of phenotype that challenge expectations based on genotype can open new therapeutic directions. One vignette traces a path from clinical observation to gene therapy; the other examines an approach to increasing red-cell energy through enhanced metabolism. Together, these stories highlight the role of bedside observations in shaping scientific questions and advancing therapies for sickle cell disease and other inherited red-cell disorders.
Learning Objectives:
- Explain how differences between observed phenotype and expected genotype can generate new hypotheses in inherited red-cell disorders.
- Describe the clinical observations and scientific reasoning that led to the gene-therapy approach presented.
- Discuss the rationale for enhancing red-cell metabolism and ATP production as a therapeutic strategy.
This page was last updated on Thursday, October 29, 2026