• Associate Professor of Pediatrics, Neonatal-Perinatal
• Associate Professor of Microbiology & Immunology
• Medical Director of Wishard Special Care Nursery

• Campus Address: 402 R4
• Telephone: (317) 278-9290
• E-mail: dclapp@iupui.edu

Hal Broxmeyer named distinguished professor at IUSM (click here for more details)

Janice Blum discusses Immunology & Infectious Diseases (click here for more details)

Training
• M.D.,1982, Indiana University School of Medicine, Indianapolis, IN
• Residency, 1982 - 1985, Pediatrics, Indiana University School of Medicine,  
  Indianapolis, IN,
• Chief Resident, 1985 - 1986, Pediatrics, Indiana University School of
  Medicine, Indianapolis, IN,
• Fellow, 1986 - 1989, Neonatology, Rainbow Babies and Children's Hospital,
  Case Western Reserve University, Cleveland, OH,
• Fellow, 1989 - 1990, Laboratory of Stanton L. Gerson, Hematopoiesis Core
  Facility Ireland Cancer Center, Case Western University, Cleveland, OH

Description and summary of research focus of the laboratory:
Dr. Clapp's laboratory is focused on understanding the molecular pathogenesis of two genetic diseases that result in both hematopoietic malignancies as well as solid tumors.   One major area of interest is to understand the role of the NF1 tumor suppressor gene.   Mutations in NF1 cause the common genetic disorder neurofibromatosis type 1 (NF1) which is associated with a predisposition to neural crest derived tumors and juvenile myelomonocytic leukemia (JMML). Neurofibromin, the protein product of the NF1 gene, functions at least in part as a GTPase activating protein that regulates the activation state of Ras proteins by stimulating their intrinsic GTPase activating activity.   Haploinsufficiency of NF1 via it's role in lineages of the tumor microenvironment is becoming increasingly appreciated to have a role in tumor progression in malignancies affecting individuals with NF1.   His laboratory provided the first genetic evidence that haploinsufficiency of NF1 alters cell fates in lineages implicated in the disease pathogenesis of neurofibromatosis type 1. Dr. Clapp's laboratory is currently interested in understanding the specific Ras effectors that are hyperactivated as a consequence of loss of the murine homologue of NF1 ( Nf1) and in utilizing murine models, as well as cellular and tissue imaging to demonstrate in vivo the role of these pathways in disease progression.

Dr. Clapp's group also has an interest in understanding the cellular and biochemical functions of an orphan group of proteins that are involved in the heterogenetic disorder Fanconi Anemia.   Fanconi anemia (FA) is characterized by a progressive bone marrow aplasia, chromosomal instability, hypersensitivity to bifunctional alkylating agents and the acquisition of malignancies.   Dr. Clapp's laboratory is focusing on the basic biology of evaluating the function of FANCC and FANCG in normal cellular homeostasis and in developing gene transfer and transplantation protocols to optimize gene transfer and engraftment of FA deficient cells using murine models.

Publications:
Gothot A, vanderLoo JCM, Clapp DW, Srour EF:  Cell cycle-related changes in repopulating capacity of mobilized peripheral blood human CD34+ cells in nonobese diabetic/scid mice.  Blood 92(8):2641-2649, 1998.

Reddy JA, Haneline LS, Srour EF, Antony AC, Clapp DW, Low PS:  Expression and functional characterization of the b-isoform of the folate receptor on CD34+ cells. Blood93(11):3940-3948, 1999.

Haneline LS, Gobbett TA, Ramani R, Carreau M, Buchwald M, Yoder MC, Clapp DW:  Loss of FancC function results in decreased hematopoietic stem cell repopulating ability.  Blood 94(1):1-9, 1999.

Ingram DA, Yang F, Travers JB, Wenning MJ, New S, Hood A, Shannon K, Williams DA, Clapp DW:  Haploinsufficiency at Nf1 modulates c-kit signaling in melanocytes and mast cells in vivo.  J. Exp. Med. 191(1):181-187, 2000.

Birnbaum RA, O'Marcaigh A, Wardak Z, Zhang Y-Y, Dranoff G, Jacks T, Clapp DW, Shannon K: Nf1 and Gmcsf interact in myeloid leukemogenesis.  Molecular Cell 5:189-195,2000.

Hiatt, KK, Zhang YY, Ingram, DA, Bollag G, Clapp DW:  Neurofibromin GAP related domains (GRDs) restore normal growth in Nf1 -/- cells.  Submitted.

Kelley MR, Tritt R, Xu Y, New S, Freie B, Clapp DW, Deutsch WA:  The Drosophilia S3 multifunctional DNA repair/ribosomal protein protects Fanconi's anemia cells against oxidative DNA damaging agents. Submitted.

Ingram DA, Hiatt K, King A, Derstine C, Wenning MJ, Travers JB, Hood A, Atkinson S, Marshall M, Clapp DW:  Heterozygosity of the Nf1 tumor suppressor gene alters multiple mast cell functions through hyperactivation of the p21ras-PI-3 kinase signaling pathway. Submitted

Search Pub Med

Return to Homepage