Settara C. Chandrasekharappa, Ph.D.

Associate Investigator
Genome Technology Branch

Director
Physical Mapping Core

Head
Gene Identification Unit

B.Sc. (Hons) Bangalore University, 1972
M.Sc. Bangalore University, 1974
Ph.D. Indian Institute of Science, 1983

(301) 402-2344 (301) 402-4929 chandra@nhgri.nih.gov		Building 49, Room 3E13 49 Convent Drive, MSC 4442 Bethesda, MD 20892-4442
Selected Publications

Our research uses genome technologies to identify disease-related genes. We explore the function of these genes in order to understand the molecular basis of pathogenesis. Our past projects succeeded in identifying the genes responsible for Multiple Endocrine Neoplasia type 1 (MEN1) and Alagille syndrome (AGS).

MEN1 is a familial cancer syndrome affecting the parathyroid, anterior pituitary and GI endocrine tissues. The tumor suppressor gene MEN1 encodes a novel protein: menin. We discovered that menin is a nuclear protein that binds the transcription factors JunD and NFkB. Menin can also repress JunD-induced and NFkB-induced transcription. We identified menin-associated gene expression changes using cDNA microarrays, and we are exploring the role of these transcripts in menin function. We isolated MEN1 homologs from mouse, frog, zebrafish and Drosophila models to perform functional analysis studies of menin.

Alagille syndrome (AGS) is a developmental disorder that affects the liver, heart, eye, face and vertebrae. We have shown that mutations in the Jagged1 (JAG1) gene are responsible for AGS. JAG1 is a ligand for a Notch receptor. The evolutionarily conserved Notch pathway plays a part in cell-fate determination during early embryonic development, and mutations in many members of this pathway cause disease in humans and mice. We isolated and characterized zebrafish Jagged homologs to further study JAG1, as the zebrafish is a particularly useful model for vertebrate development.

I am the director of the Physical Mapping Core laboratory, which provides library screening, gene mapping and other genome-related services for the investigators in our institute.