Raman Sood, Ph.D.

Dr. Raman Sood obtained her B.Sc. and M.Sc. Honors degrees in biology from Guru Nanak Dev University in Amritsar, India, her Ph.D. from Queen’s University, Kingston, Canada, and post-doctoral training at Hospital for Sick Children in Toronto, Canada. She has been at the National Institutes of Health since 1994, first at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and at the National Human Genome Research Institute (NHGRI) since 1997. Dr. Sood was appointed as an NHGRI associate investigator in 2001.

Dr. Sood’s long-term research interest has been to understand the molecular basis of human genetic disorders. After participating in several research projects aimed at identification of the susceptibility genes in simple and complex genetic disorders, and concomitant with the completion of the Human Genome project, she became interested in the functional genomic analyses of genes using the zebrafish model. With expert advice from Drs. Paul Liu and Shawn Burgess, she founded the NHGRI Zebrafish Core and has been its director since 2006. Dr. Sood has learned and applied genetic, genomic and bioinformatics tools to her research ranging from genome-wide association studies to positional cloning to functional genomic analyses using animal models. She has participated in several collaborative research projects and published more than 80 papers in peer-reviewed journals.

Dr. Sood’s primary research interest is to perform functional genomic analyses of genes to understand their role in normal development and disease processes by applying cutting-edge molecular biology tools, genomic technologies and zebrafish as a model system. In the Translational and Functional Genomics Branch Oncogenesis and Development Section, her research focuses on understanding the genetic regulation of hematopoiesis and genetic and genomic events that lead to leukemogenesis, particularly acute myeloid leukemia involving mutations or chromosomal rearrangements of the core binding factors, RUNX1 and CBFB.

For studies aimed at understanding the genetic regulation of hematopoiesis, Dr. Sood has generated and characterized gene knockout mutants for several important hematopoietic genes. Through the study of mutations in gata1 and runx1, two of the major transcriptional regulators of primitive and definitive hematopoiesis, respectively, Dr. Sood has demonstrated differential requirements of these genes during distinct waves of hematopoiesis. For studies aimed at understanding the process of leukemia development in patients with chromosomal rearrangements of the core binding factors, Dr. Sood performed whole exome sequencing of tumor samples to identify cooperating somatic mutations. Her work led to the identification of a specific point mutation in DHX15, an RNA helicase required for splicing, thus highlighting the importance of properly functioning splicing machinery in leukemogenesis.

Animal models play a critical role in understanding the genetic regulation of normal development and disease pathophysiology. Zebrafish as a vertebrate model offers several advantages, such as external fertilization, high fecundity, optically transparent embryos, rapid embryo development, and conserved pathways for the majority of biological processes. Furthermore, zebrafish orthologs have been identified for ~85% of genes associated with human diseases. Therefore, when a candidate gene for a disease or biological process is identified through the application of genomic technologies, (e.g., whole exome sequencing or transcriptome profiling), zebrafish models can be established to validate its role in the disease process, understand disease mechanism and develop targeted therapeutics.

Dr. Sood, with advice from Drs. Liu and Burgess, established the NHGRI Zebrafish Core in 2006 to facilitate the use of the zebrafish model by NHGRI investigators for their research. As the core's director, Dr. Sood’s work includes management of the day-to-day core activities and implementation of new approaches to increase the throughput and quality of core services while reducing cost. Under Dr. Sood’s guidance, core staff provide services (microinjections, whole mount in situ hybridization, generation of genetic mutants and transgenic lines, cryopreservation, in vitro fertilization to recover frozen lines); training (handling and breeding, monitoring embryo development, imaging, whole mount in situ hybridization); and maintain several commonly used wild type, mutant and transgenic zebrafish lines.

Since its inception, the core has adopted new technical developments in the field of zebrafish research and developed protocols and resources so that all NHGRI investigators can apply cutting-edge methodologies to their research.

In particular, the core developed efficient high throughput protocols for targeted mutagenesis using genome editing nucleases, particularly CRISPR/Cas9 to generate single or multiple gene knockout mutants in zebrafish. To date, the core has generated gene knockout zebrafish lines for over 200 genes involved in diverse cellular and developmental processes such as DNA repair, hematopoiesis, immunity, metabolic diseases, regeneration and specific phenotypes studied by NHGRI investigators. Upon generation of mutant lines, the Zebrafish Core helps researchers with in-depth phenotype analysis by morphological, histological and biochemical assays. Recently, the core has developed efficient screening methods for generation of zebrafish models with targeted knock-in of desired sequences or point mutations seen in human patients. These tools will allow NHGRI researchers to expand the use of zebrafish in their research.