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Laura S. Haneline, M.D.

Professor of Microbiology & Immunology
Professor of Pediatrics

Description and summary of research focus of the laboratory

The overall focus of my laboratory is to understand how mutations in Fanconi anemia (FA) genes perturb hematopoietic cell proliferation, self-renewal, and survival in order to develop novel treatment strategies to delay or prevent bone marrow failure and/or leukemia in FA patients. Fanconi anemia (FA) is a complex, autosomal recessive disorder characterized by genomic instability, bone marrow (BM) failure, and increased incidence of malignancies.   Eleven complementation groups of FA (FA-A through FA-L) have been identified, and eight of the genes have now been cloned.   However, the function(s) that individual FA proteins have in maintaining genome integrity remain unclear. Determining the mechanism(s) that FA proteins affect multiple complex intracellular processes (chromosomal stability, cell cycle, apoptosis, and growth) may lead to novel treatment strategies for FA patients that could potentially delay onset of BM failure and/or malignancy.  Currently, there are three main focuses of our laboratory.   1) Evaluation of HSC function in Fanconi anemia complementation type C deficient ( Fancc -/- ) and ( Fance -/- ) mice.   By interrogating HSC function in FA murine models, we have previously identified a number of mechanisms involved in the pathogenesis of BM failure and leukemogenesis.   2) Determine whether introduction of recombinant Fancc or Fancc mutants will restore normal HSC function. Using retroviral, lentiviral, and foamyviral vectors, we are evaluating whether Fancc -/- HSC defects are reversible and whether identified functional domains within the Fancc protein have a role in maintenance of HSC activity.   3) Determine whether FANCC has a direct role in regulating redox-signaling pathways.   Our recent studies show that Fancc -/- progenitors are highly sensitive to multiple oxidative stimuli.   We have identified aberrant regulation of an important redox-dependent protein in Fancc -/- cells.   Future studies are evaluating the mechanism by which FANCC inhibits redox-regulated proteins.

  • Haneline LS , Broxmeyer HE, Cooper S, Hangoc G, Carreau M, Buchwald M, Clapp DW: Multiple inhibitory cytokines induce deregulated progenitor growth and apoptosis in hematopoietic cells from Fac -/- mice. Blood 91(11):4092-4098, 1998.
  • Haneline LS , Gobbett TA, Ramani R, Carreau M, Buchwald M, Yoder MC, Clapp DW. Loss of Fanc C function results in decreased hematopoietic stem cell repopulating ability. Blood 94(1):1-9, 1999 (Plenary paper).
  • Haneline LS , Li X, Ciccone SLM, Hong P, Yang Y, Lee S-H, Orazi A, Srour EF, Clapp DW. Retroviral-Mediated Expression of Recombinant Fancc Enhances the Repopulating Ability of Fancc -/- Hematopoietic Stem Cells and Decreases the Risk of Clonal Evolution . Blood 101(4):1299-1307, 2003.
  • Li X, Plett A, Yang Y, Hong P, Freie B, Srour EF, Orschell CM, Clapp DW, Haneline LS . Fanconi Anemia Type C Deficient Hematopoietic Stem/Progenitor Cells Exhibit Aberrant Cell Cycle Control. Blood, 102(6):2081-2084, 2003.
  • Saadatzadeh MR, Bijangi-Vishehsaraei K, Hong P, Bergman H, and Haneline LS . Oxidant Hypersensitivity of Fanconi Anemia Type C Deficient Cells is Dependent on a Redox-Regulated Apoptotic Pathway. J Biol Chem. 2004 Apr 16; 279(16):16805-12. Epub   2004 Feb 05.

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  • B.S. Ball State University, Muncie, IN, 1987
  • M.D. Indiana University School of Medicine, Indpls., IN, 1991

Department of Microbiology and Immunology | IU School of Medicine | 635 Barnhill Drive, MS 420 | Indianapolis, IN 46202 | (317) 274-0506