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Director

Zebrafish Core

Education

M.Sc. Guru Nanak Dev University, India, 1984

Ph.D. Queen's University, Kingston, Canada, 1989

Biography

Dr. Raman Sood obtained her B.Sc. and M.Sc. Honors degrees in biology from Guru Nanak Dev University in Amritsar, India. She obtained her Ph.D. training at Queen's University, Kingston, Canada, and post-doctoral training at Hospital for Sick Children in Toronto, Canada. She has been at National Institutes of Health since 1994, first at National Institute of Arthritis and Musculoskeletal and Skin diseases (NIAMS) and then at National Human Genome Research Institute (NHGRI) since 1997. At NHGRI Dr. Sood was appointed as an 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 genomics analysis of genes using zebrafish model. With expert advice from Paul Liu, Ph.D., and Shawn Burgess, Ph.D., she started the NHGRI Zebrafish Core and has been its director since 2005. 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 genomics analysis using animal models. She has participated in several collaborative research projects and published more than 50 papers in peer-reviewed journals.

Scientific Summary

Dr. Sood's primary research interest is to perform functional genomic analysis 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 Oncogenesis and Development Section (ODS), her research focus is the genetic regulation of hematopoiesis and genetic and genomic events that lead to leukemogenesis, particularly acute myeloid leukemia involving chromosomal rearrangements of the core binding factors.

For studies aimed at understanding the genetic regulation of hematopoiesis, Dr. Sood performed reverse genetic screens in zebrafish to generate novel 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. These mutants provide tools for understanding the mechanism of hematopoiesis, particularly emergence and differentiation of hematopoietic stem cells and developing new therapeutics for blood disorders by high-throughput chemical screening.

Animal models play a critical role in understanding the genetic regulation of normal development and disease pathophysiology. Recent developments in sequencing technologies have allowed researchers to apply whole exome sequencing to identify candidate genes with putative disease-causing variants in patients with rare diseases. To identify the causative gene from this list of candidate genes requires cell-based and in vivo animal models. Zebrafish as a vertebrate model for functional genomics gained popularity in the last decade with the development of technologies for forward and reverse genetic screens to identify genotype-phenotype correlations.

Zebrafish model for functional genomics

Dr. Sood, with advice from Paul Liu, Ph.D., and Shawn Burgess, Ph.D., established the NHGRI Zebrafish Core in 2005 to facilitate functional genomics analysis of candidate genes by NHGRI investigators. As the director of the Zebrafish Core, 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 the core services while reducing cost. Under Dr. Sood's guidance, the core staff provides services (microinjections, whole mount in situ hybridization, generation of genetic mutants and transgenic lines, cryopreservation, imaging, in vitro fertilization to recover frozen lines), training (handling and breeding, monitoring embryo development, imaging, whole mount in situ hybridization) and maintains several commonly used wild type, mutant and transgenic zebrafish lines.

Since its inception, the Zebrafish 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 both random and targeted mutagenesis approaches to generate genetic mutants in zebrafish. For random mutagenesis, >3,000 males heterozygous for N-ethyl-N-nitrosourea (ENU)-induced random point mutations were generated and screened by Targeting Induced Local Lesions IN Genomes (TILLING) () to identify missense and truncation mutations in several genes.

For targeted mutagenesis, Dr. Sood has developed cost-effective methods to efficiently generate knockout alleles using new genome-editing tools, such as zinc-finger, tal-effector and CRISPR/cas nucleases (ZFNs, TALENs and RGENs). The core applies a two-pronged approach to the functional analysis of candidate genes. First, a transient knockdown model is established using antisense morpholinos to investigate the effect on embryonic development. In parallel, genetic mutants are generated for evaluation of larval and adult phenotypes. To date, Dr. Sood has generated mutant zebrafish lines for over 50 genes involved in diverse cellular and developmental processes such as DNA repair, hematopoiesis, immunity, metabolic diseases, cancer and rare phenotypes studied by the NIH Undiagnosed Diseases Program. Upon generation of mutant lines, the zebrafish core helps researchers with in depth phenotype analysis by morphological, histological and biochemical assays

Publications

International FMF Consortium. Ancient missense mutations in a new member of the RoRet gene family are likely to cause familial Mediterranean fever. Cell, 90: 797-807. 1997. [PubMed]

Sood R, Bonner TI, Makalowska I, Stephan DA, Robbins CM, Connors TD, Morgenbesser SD, Su K, Pinkett H, Faruque MU, Graham C, Baxevanis AD, Klinger KW, Landes GM, Trent JM and Carpten JD. Cloning and characterization of 13 novel transcripts and the human RGS8 gene from the 1q25 region encompassing the hereditary prostate cancer (HPC1) locus. Genomics, 73: 211-222. 2001. [PubMed]

Pollock PM, Cohen-Solal K, Sood R, Namkoong J, Martino JJ, Koganti A, Zhu H, Robbins C, Makalowska I, Shin S-S, Martin Y, Roberts KG, Yudt LM, Chen A, Cheng J, Incao A, Pinkett HW, Graham CL, Dunn K, Crespo-Carbone SM, Mackason KR, Ryan KB, Sinsimer D, Goydos J, Reuhl KR, Eckhaus M, Meltzer PS, Pavan WJ, Trent JM, and Chen S. Melanoma mouse model implicates metabotropic glutamate signaling in melanocytic neoplasia. Nat Genet, 34: 108-112. 2003. [Full Text]

Zhang J., Wheeler D., Yakub I., Wei S., Sood R., Rowe W., Liu P.P., Gibbs R. and Buetow K. SNPDetector: a software tool for sensitive and accurate SNP detection. PLoS Computational Biology, 1: 0395-0404. 2005. [PubMed]

Sood R, English MA, Jones M, Mullikin J, Wang DM, Anderson M, Wu D, Chandrasekharappa SC, Yu J, Zhang J, Paul Liu P. Methods for reverse genetic screening in zebrafish by resequencing and TILLING. Methods, 39: 220-227. 2006. [PubMed]

Jin H, Sood R, Xu J , Zhen F, English MA, Liu PP and Wen Z. Definitive hematopoietic stem/progenitor cells manifest distinct differentiation output in the zebrafish VDA and PBI. Development, 136: 647-654. 2009. [PubMed]

Belele CL, English MA, Chahal J, Burnetti A, Finckbeiner SM, Gibney G, Kirby M, Sood R and Liu PP. Differential requirement for Gata1 DNA binding and transactivation between primitive and definitive stages of hematopoiesis in zebrafish. Blood, 114: 5162-5172. 2009. [PubMed]

Sood R, English MA, Belele CL, Jin H, Bishop K, Haskins R, McKinney MC, Chahal J, Weinstein BM, Wen Z and Liu PP. Development of multi-lineage adult hematopoiesis in the zebrafish with a runx1 truncation mutation. Blood, 115(14):2806-9. 2010. [PubMed]

Shive HR, West RR, Embree LJ, Azuma M, Sood R, Liu P and Hickstein DD. Brca2 in zebrafish ovarian development, spermatogenesis, and tumorigenesis. PNAS, 107: 19350-19355. 2010. [PubMed]

Gao B, Song H, Bishop K, Elliot G, Garrett L, English M, Andre P, Robinson J, Sood R, Minami Y, Economides AN, and Yang Y. Wnt signaling gradients establish planar cell polarity by inducing Vangl2 phosphorylation through Ror2. Developmental Cell, 20: 163-176. 2011. [PubMed]

Sood R and Liu PP. Novel insights into the genetic controls of primitive and definitive hematopoiesis from zebrafish models. Advances in Hematology, 2012:830703. 2012. [PubMed]

Sood R, Carrington B, Bishop K, Jones MP, Rissone A, Candotti F, Chandrasekharappa SC, Liu P. Efficient Methods For Targeted Mutagenesis in Zebrafish Using Zinc-Finger Nucleases: Data From Targeting of Nine Genes Using CompoZr or CoDA ZFN. PLos One, 8:e57239. 2013. [PubMed]

Vilboux T, Lev A, Malicdan MC, Simon AJ, Jarvinen P, Racek T, Puchalka J, Sood R, Carrington B, Bishop K, Mullikin J, Huizing M, Garty BZ, Eyal E, Wolach B, Gavrieli R, Toren A, Soudack M, Atawneh OM, Babushkin T, Schiby g, Cullinane A, Avivi C, Polak-Charcon S, Barshack I, Amariglio N, Rechavi G, van der Werff ten Bosch J, Anikster Y, Klein C, Gahl WA, Somech R. A congenital neutrophil defect syndrome associated with mutations in VPS45. N Eng J Med, 369: 54-65. 2013. [PubMed]

Zhou Q, Yang D, Ombrello AK, Zavialov AV, Toro C, Zavialov AV, Stone DL, Chae JJ, Rosenzweig SD, Bishop K, Barron KS, Kuehn HS, Hoffman P, Negro A, Tsai WL, Cowen EW, Pei W, Milner JD, Silvin C, Heller T, Chin DT, Patronas NJ, Barber JS, Lee CR, Wood GM, Ling A, Kelly SJ, Kleiner DE, Mullikin JC, Ganson NJ, Kong HH, Hambleton S, Candotti F, Quezado MM, Calvo KR, Alao H, Barham BK, Jones A, Meschia JF, Worrall BB, Kasner SE, Rich SS, Goldbach-Mansky R, Abinum M, Chalom E, Gotte AC, Punaro M, Pascual V, Verbsky JW, Torgerson TR, Singer NG, Gershon TR, Ozen S, Karadag O, Fleisher TA, Remmers EF, Burgess SM, Moir SL, Gadina M, Sood R, Hershfield MS, Boehm M, Kastner DL, Aksentijevich I. Early-onset stroke and vasculopathy associated with mutations in ADA2. N Eng J Med, 370: 911-920. 2014. [PubMed]

Bresciani E, Carrington B, Wincovitch S, Jones M, gore AV, Weinstein BM, Sood R, and Liu P. CBFb and RUNX1 are required at two different steps during the development of hematopoietic stem cells in zebrafish. Blood, pii: blood-2013-10-531988. Epub ahead of print. 2014. [PubMed]

Sood R, Hansen N, Donovan FX, Carrington B, Bucci D, Maskeri B, Young A, Trivedi NS, Kohlschmidt J, Stone RM, Caligiuri M, Chandrasekharappa SC, Marcucci G, Mullikin JC, Bloomfield CD and Liu P. Somatic mutational landscape of AML with inv(16) or t(8;21) identifies patterns of clonal evolution in relapse leukemia. Leukemia, 2015. doi: 10.1038/leu.2015.141. [PubMed]

Carrington B, Varshney GK, Burgess SM, Sood R. CRISPR-STAT: an easy and reliable PCR-based method to evaluate target-specific sgRNA activity. Nucleic Acids Research, doi: 10.1093/nar/gkv802. 2015. [PubMed]

Varshney GK, Pei W, LaFave MC, Idol J, Xu L, Gallardo V, Carrington B, Bishop K, Jones MP, Li M, Harper U, Huang SC, Prakash A, Chen W, Sood R, Ledin J, and Burgess SM. High throughput gene targeting and phenotyping in zebrafish using CRISPR/Cas9. Genome Res, 25(7):1030-42. 2015. [PubMed]

Rissone A, Weinacht KG, Marca G, Bishop K, Giocaliere E, Jagadeesh J, Felgentreff K, Dobbs, K, Al-Herz W, Jones MP, Chandrasekharappa S, Kirby M, Wincovitch S, Simon KL, Itan Y, DeVine A, Schlaeger T, Schambach A, Sood R, Notarangelo LD, Candotti F. Reticular dysgenesis-associated AK2 protects hematopoietic stem and progenitor cell development from oxidative stress. J Exp Med, 212 (8): 1185-1202. 2015.[PubMed]

Zebrafish Core Staff

Generic Profile Photo
Kevin S. Bishop, B.S.
  • Biologist
  • Zebrafish Core
Blake Carrington
Blake Carrington, B.S.
  • Biologist
  • Zebrafish Core

Last updated: November 15, 2016