Raman Sood, Ph.D.
Translational and Functional Genomics Branch
M.Sc., Guru Nanak Dev University, India
Ph.D., Queen's University, Kingston, Canada
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.
Shin U, Nakhro K, Oh C-Y, Carrington B, Song H, Varshney GK, Kim Y, Song H, Jeon S, Robbins G,, Kim S, Yoon S, Choi YJ, Kim YJ, Burgess S, Kang S, Sood R, Lee Y, Myung KJ. 2021. Large-scale generation and phenotypic characterization of zebrafish CRISPR mutants of DNA repair genes. DNA Repair 107: 103173.
Bresciani E, Carrington B, Yu K, Kim E, Zhen T, Guzman V, Broadbridge E, Bishop K, Kirby M, Harper U, Wincovitch, Dell’Orso S, Sartorelli V, Sood R, Liu P. 2021. Redundant mechanisms driven independently by RUNX1 and GATA2 for hematopoietic development. Blood Advances 5 (23): 4949-4962.
Hong SK, Hu P, Jang JH, Carrington B, Sood R, Roessler E, Muenke M. 2020. Functional analysis of Sonic Hedgehog variants associated with holoprosencephaly in humans using a CRISPR/Cas9 zebrafish model. Human Mutation , 41 (12): 2155-2166.
Carrington B, Weinstein RN, and Sood R. BE4max and AncBE4max are efficient in germline conversion of C:G to T:A base pairs in zebrafish. cells 9(7): 1690. 2020.
Han CR, Holmsen E, Carrington B, Bishop K, Zhu YJ, Starost M, Meltzer P, Sood R, Liu P, and Cheng S-Y. Generation of novel genetic models to dissect resistance to thyroid hormone receptor a in zebrafish. Thyroid 30 (2):314-328. 2020.
McElderry J, Carrington B, Bishop K, Kim E, Pei W, Chen Z, Ramanagoudr-Bhojappa R, Prakash A, Burgess SM, Liu PP, and Sood R. Splicing factor DHX15 affects tp53 and mdm2 expression via alternate splicing and promoter usage. Hum Mol Genet 28 (24):4173-4185. 2019.
Paul CD, Bishop K, Devine A, Paine EL, Staunton JR, Thomas SM, Thomas JR, Doyle AD, Jenkins LMM, Morgan NY, Sood R, Tanner K. Tissue architectural cues drive organ targeting of tumor cells in zebrafish. Cell Systems, 9 (2): 187-206. 2019.
Ramanagoudr-Bhojappa R, Carrington B, Ramaswami M, Bishop K, Robbins GM, Jones M, Harper U, Frederickson SC, Kimble DC, Sood R*, Chandrasekharappa SC*. Multiplexed CRISPR/Cas9-mediated knockout of Fanconi anemia pathway genes in zebrafish revealed their roles in growth, sexual development and fertility. PLoS Genet 14 (12): e1007821. 2018.
Justice CM, Kim J, Kim S-D, Kim S-N, Kim K, Yagnik G, Cuellar A, Carrington B, Lu C-L, Sood R, Boyadjiev SA, Wilson A. A variant associated with sagittal nonsyndromic craniosynostosis alters the regulatory function of a non-coding element. Am J Med Genet A, 173: 2893-2897. 2017 .
Watkins-Chow DE, Varshney GK, Garrett LJ, Chen Z, Jimenez EA, Rivas C, Bishop KS, Sood R, Harper UL, Pavan WJ, and Burgess SM. Highly-efficient Cpf1-mediated gene targeting in mice following high concentration pronuclear injection. G3. Genes| Genomes| Genetics : 7: 719-722. 2017.
Varshney GK*, Carrington B*, Pei W, Bishop K, Chen Z, Fan C, Xu L, Jones M, LaFave MC, Ledin J, Sood R and Burgess SM. A High-throughput workflow for CRISPR/ Cas9 mediated targeted mutagenesis in zebrafish. Nature Protocols : 11: 2357- 2375. 2016.
Sood R, Hansen NF, Donovan FX, Carrington B, Bucci D, Maskeri B, Young A, Trivedi NS, Kohlschmidt J, Stone RM, Caligiuri MA, Chandrasekharappa SC, Marcucci G, Mullikin JC, Bloomfield CD, and Liu P. 2015. Somatic mutational landscape of AML with inv(16) or t(8:21) identifies patterns of clonal evolution in relapse leukemia. Leukemia 30: 501-504. 2016.
Carrington B, Varshney GK, Burgess SM and Sood R. CRISPR-STAT: an easy and reliable PCR-based method to evaluate target-specific sgRNA activity. Nucleic Acids Res 43 (22): 2157. 2015.
Rissone A, Weinacht KG, la Marca G, Bishop K, Giocaliere E, Jagadeesh J, Felgentreff K, Dobbs K, Al-Herz W, Jones M, 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.
Varshney GK, Pei W, LaFave MC, Idol J, Xu L, Gallardo V, Carrington B, Bishop K, Jones M, Li M, Harper U, Huand 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): 1030-1042, 2015.
Bresciani E, Carrington B, Wincovitch S, Jones MP, Gore AV, Weinstein BM, Sood R, Liu PP. CBFB and RUNX1 are required at 2 different steps during the development of hematopoietic stem cells in zebrafish. Blood 124: 70-78, 2014.
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 ZFNs. PLoS One 8: e57239, 2013.
Shive HR, West RR, Embree LJ, Azuma M, Sood R, Liu P and Hickstein DD. Brca2 in zebrafish ovarian development, spermatogenesis, and tumorigenesis. Proc Natl Acad Sci USA 107: 19350-19355, 2010.
Sood R, English MA, Belele C, Jin B, 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 115:2806-9, 2010.
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.
Jin H*, Sood R*, Xu J, Zhen F, English M, Liu PP, Wen Z. Definitive hematopoietic stem/progenitor cells manifest distinct differentiation output in the zebrafish VDA and PBI. Development 136:647-54, 2009.
Sood R, English MA, Jones M, Mullikin J, Wang DM, Anderson M, Wu D, Chandrasekharappa SC, Yu J, Zhang J, and Liu PP. Methods for reverse genetic screening in zebrafish by resequencing and TILLING. Methods 39:220-227, 2006.
Zhang J, Wheeler D, Yakub I, Wei S, Sood R, Rowe W, Liu PP, Gibbs R, and Buetow K. SNPDetector: a software tool for sensitive and accurate SNP detection. PLoS Computational Biology 1: 0395—0404, 2005.
Sood R, Makalowska I, Galdzicki M, Hu P, Eddings E, Robbins CM, Moses T, Namkoong J, Chen S, and Trent JM. Cloning and characterization of a novel gene, SHPRH, encoding a conserved putative protein with SNF2/helicase and PHD-finger domains from the 6q24 region. Genomics 82: 153-161, 2003.
Pollock PM*. Cohen-Solal K*, Sood R*, Namkoong J, Martino JJ, Koganti A, Zhu H, Robbins C, Makalowska I, Shin S-S, Marin 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.
Carpten J, Nupponen N, Isaacs S, Sood R, Robbins C, Xu J, Faruque M, Moses T, Ewing C, Gillanders E, Hu P, Bujnovszky P, Makalowska I, Baffoe-Bonnie A, Faith D, Smith J, Stephan D, Wiley K, Brownstein M, Gildea D, Kelly B, Jenkins R, Hostetter G, Matikainen M, Schleutker J, Klinger K, Connors T, Xiang Y, Wang Z, De Marzo A, Papadopoulos N, Kallioniemi O-P, Burk R, Meyers D, Gronberg H, Meltzer P, Silverman R, Bailey-Wilson J, Walsh P, Isaacs W, Trent J. Germline mutations in the ribonuclease L gene in families showing linkage with HPC1. Nat Genet 30: 181-184, 2002.
Sood R*, Bonner T*, Makalawska I, Stephan D, Robbins CM, Connors TD, Morgenbesser SD, Su K, Pinkett H, Faruque M, Graham C, Baxevanis A, Klingler K, Landes G, Trent J, and Carpten J. 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.
Sood R, Blake T, Aksentijevich I, Wood G, Chen X, Gardner D, Shelton DA, Pras E, Balow JE, Centola M, Deng Z, Zaks N, Chen XG, Richards N, Fischel-Ghodsian N, Rotters JI, Pras M, Shohat M, Deaven LL, Gumucio DL, Callen DF, Richards RI, Collins FS, Liu PP, Kastner DL, and Doggett NA. Construction of a 1-mb restriction-mapped cosmid contig containing the candidate region for the familial Mediterranean fever locus (MEFV) on chromosome p13.3. Genomics 42:83-95, 1997.
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.
Sood R, Bear C, Auerbach W, Reyes E, Jensen T, Riordan JR and Buchwald M. Regulation of CFTR expression and function during differentiation of intestinal epithelial cells. EMBO J 11(7): 2487-2494, 1992. PMID 1378393.
Sood R, Mulligan LM, Poon R, White BN and Holden JJA. Genetic mapping of two new DNA markers in Xq26-q28 relative to the fragile X syndrome locus. Am J Hum Genet 47(3): 395-401, 1990.
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Last updated: June 16, 2022