I have received clinical education in Internal Medicine and Hematology. My research training was in immunology, immunohematology and stem cell biology. My current line of research includes targeted clinical trials and translational studies focusing on clarification of the pathophysiology and…
more pathogenesis of bone marrow failure syndromes, including aplastic anemia and myelodysplastic syndrome as well as closely related model diseases such as paroxysmal nocturnal hemoglobinuria or large granular lymphocyte leukemia. My studies encompass various aspects of these diseases such as stem cell and progenitor failure (numerical contraction and functional defects) and inhibitory effects of the cellular immune system leading to impaired function of the hematopoietic stem cell compartment by direct cytotoxicity or via inhibitory cytokines. The basic aspects of these investigations include molecular analysis of the T cell receptor (TCR) repertoire and applications of clonotypic TCR diagnostics to study immune-mediated hematologic disease. Finally, the most recent investigations address various clinical and molecular aspects of the evolution of clonal disease with acquisition of chromosomal damage by hematopoietic stem cells culminating in the development of hematologic malignancies. Specifically, these studies deal with the nature and types of chromosomal damage in myelodysplasia and the mechanisms leading to chromosomal instability including genetic predisposition to bone marrow failure syndromes. The experimental tools include high-density single nucleotide polymorphism arrays and molecular assays to investigate DNA repair and signal transduction pathways in hematopoietic progenitor cells. The goals of my research are to identify pathophysiologic pathways and molecular targets for diagnostic and therapeutic applications.
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