Raman Sood, Ph.D.
Genetics and Molecular Biology Branch
M.Sc. Guru Nanak Dev University, India, 1984
Ph.D. Queen's University, Kingston, Canada, 1989
6 Center Dr, MSC 0612
Bethesda, MD 20892-0612
Dr. Sood's research is aimed towards developing resources and adopting new technologies to facilitate the functional analysis of genes involved in human genetic diseases using the zebrafish as a model organism. Her goal is to adopt new technical developments in the field of zebrafish research so that all NHGRI investigators can capitalize on these cutting-edge methodologies.
Animal models with gain or loss of function mutations in genes play an important role in functional genomic studies, developing models for understanding the pathophysiology of diseases, and novel therapeutic approaches. To achieve this goal using the zebrafish as a model system, Dr. Sood utilizes two complementary approaches: TILLING (for "targeting induced local lesions in genomes") and zinc-finger nuclease mediated mutagenesis. Both of these methods can be used to generate genetic mutants in genes of interest for her group and other NHGRI investigators.
For the first method, known as TILLING, Dr. Sood's laboratory undertook a large-scale N-ethyl-N-nitrosourea (ENU) mutagenesis approach to generate ~3500 zebrafish males heterozygous for random point mutations throughout their genomes. Reverse genetic approaches involving polymerase chain reaction (PCR) and sequencing of exons coding for functional domains are used to identify mutants for genes of interest. Once candidate mutations are identified, new fish lines are then generated and bred to homozygosity in an effort to better understand the resulting phenotypes. To date, Dr. Sood has generated over a dozen lines with missense and truncation mutations in genes involved in diverse cellular and developmental processes such as DNA repair, hematopoiesis, gastrulation, and cancer.
In the other method of mutant generation, Dr. Sood's group microinjects mRNA-encoding zinc finger nucleases specifically targeting the gene of interest into one-cell stage zebrafish embryos. The injected embryos, or "founders," are grown to adulthood, which takes approximately three months, and are screened for germline transmission of mutations induced by the zinc finger nucleases. The phenotypes are then analyzed by crossing the heterozygous mutant fish. Using this method, Dr. Sood has identified several different mutants with frame-shift mutations and premature truncations in cbfb, a gene involved in regulation of hematopoiesis.
Dr. Sood has a long-standing interest in understanding the process of cancer development and progression. In parallel with the technical development work being conducted in the Zebrafish Core, Dr. Sood has collaborated with Dr. Paul Liu to characterize the phenotypes of zebrafish mutations in genes involved in hematopoiesis; mutations in several genes that control hematopoiesis cause leukemias and lymphomas.
Through the study of novel zebrafish mutations in gata1 and runx1, two of the major regulators of primitive and definitive hematopoiesis, respectively, Drs. Sood and Liu have demonstrated differential requirements of these genes during different waves of hematopoiesis. These mutants provide tools for clarifying the mechanism of hematopoiesis and developing new therapeutics by high-throughput chemical screening.
Last Updated: September 20, 2011