Naveen Manchanda, MD
ASH takes inspiration from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) as it celebrates its anniversary. Over the past 60 years, researchers associated with this institute have supported pioneering work in their field as well as contributed vastly to the field of hematology. This anniversary will be celebrated with a series of talks on hematopoietic stem cells, new roles for red cells, and hemoglobin, and will end with an appropriate description of the Golden Age of Iron Biology.
Hematopoiesis has led the field of developmental cell biology with the concept of stem cells and their ordered progression to progeny developing into cells with different fates. Several decades of work have provided a breadth of understanding about how hematopoiesis occurs in an orderly and coordinated fashion. Dr. Kenneth Kaushansky will provide insight into the manifold aspects of this process including cell signaling, survival, proliferation, receptor-ligand interactions, and other processes that exert control over this precisely regulated entity. He will also outline avenues for further research in this area.
Dr. Alan Schechter will present an overview of research into the molecular physiology of hemoglobin. The red cell and its incorporated hemoglobin share a unique relationship to ensure a maximal concentration of hemoglobin that can be ferried around and kept safe from the molecular stresses of oxidation. Hemoglobin, apart from being a carrier for oxygen, is also adept in other recently identified processes. One process identified was the generation of nitric oxide in a hypoxic environment to decrease vascular tone, with allosteric control. Severe hemolytic states can induce the opposite reaction with further oxidation of excess hemolobin into methoglobin. Whether this process can be reversed by intake of nitrite-generating agents and induce vasodilation in hemolytic states is the focus of current research.
Iron was the often-neglected child of human biology; reassuringly, this was not by design. Understanding the basic elements of iron physiology took an enormous amount of time and effort, as iron appeared to horde its secrets well. The only element that we infuse as well as chelate, iron has been more often used than understood. Enter the ’90s, when there was an increased availability of products to infuse iron that were safer and easier to administer. Soon there were products to chelate iron that were effective and also easier to administer. Paralleling this was an increase in the understanding of basic physiology of iron and its relationship to hemochromatosis, anemia of inflammation, and a host of other conditions. Hepcidin, a central regulatory protein in iron metabolism, was also discovered and characterized around this time. There has been a veritable explosion of knowledge about iron over the past years. The dynamics of iron utilization at the molecular level, during the process of absorption from the gut and utilization in the marrow, have been more clearly defined. Knowledge about both ordered and disordered iron states in the body increased. Dr. Nancy Andrews will discuss the remarkable expansion of knowledge about the control of iron balance, highlight advances, and outline challenges that remain in this field.
Dr. Manchanda indicated no relevant conflicts of interest.