Laura Haneline MD
Associate Professor of Pediatrics and Microbiology & Immunology
James W. Riley Hospital for Children
M.D., Indiana University School of Medicine, 1991
Internship and Residency, Indiana University School of Medicine, 1991 - 1994
Fellowship, Indiana University School of Medicine, 1994 - 1997
In my laboratory, there are two main areas of investigation. The first area focuses on basic studies to understand the pathogenesis of bone marrow failure and leukemogenesis in the genetic disease Fanconi anemia (FA). FA is a complex, autosomal recessive disorder characterized by chromosomal instability, bone marrow (BM) failure, increased incidence of malignancies, and hypersensitivity to multiple classes of DNA damaging agents. Thirteen FA genes have been cloned, however the functions of individual proteins remain unclear. Our overall goals are to determine the mechanisms by which FA proteins affect multiple complex intracellular processes, which may lead to novel treatment strategies that could potentially delay onset of BM failure and/or malignancy. Previously, we showed that FA type C deficient (Fancc -/-) hematopoietic stem cells (HSCs) have decreased primary and secondary repopulating abilities compared to wildtype HSCs. In addition, we showed that Fancc -/- HSCs and progenitor cells exhibit altered cell cycle control, which may predispose cells to injury from cell cycle specific agents. Most recently, we found that Fancc -/- progenitor cells are hypersensitive to multiple oxidative stimuli. We are currently evaluating the biochemical and molecular mechanisms responsible for enhanced oxidant sensitivity in FA in order to elucidate potential molecular targeted therapies.
The second area of investigation in the lab is based on the observation that infants born to mothers with diabetes during pregnancy have an increased risk to develop hypertension in childhood and adulthood. Based on these clinical observations, we hypothesize that a fetus exposed to a diabetic intrauterine environment develops structural and functional changes in the vascular system, specifically endothelial progenitor cells. We recently demonstrated that neonatal endothelial progenitor cells or endothelial colony forming cells (ECFCs) from infants of diabetic mothers (type 1 and type 2) exhibit enhanced senescence and reduced vessel forming ability. Future studies to explore the molecular mechanisms responsible for this phenotype are planned using human and rogent model systems. Therefore, this area of investigation includes both basic and translational studies.
