Information

Related Research Units

The Manton Center for Orphan Disease Research
Genetics and Genomics Research

Research Overview

Since 2017, Shira has been leading the Data Science team within the Research Computing group, during which time the team deployed of two major initiatives:

  • BCH cohort sequencing project – The Children’s Rare Disease Cohorts Initiative – the project integrates sample collection from over 10,000 families, genomic sequencing, analysis and clinical follow-ups;
  • deployment of institutional bioinformatics support to the BCH research community – operationalized by a collaborative team of bioinformaticians that foster novel research and holistically consult, develop and deploy tools, train and provide best practices regarding the experimental design, analysis, integration and visualization of data from wide ranging experiments, including transcriptomic (e.g., single cell and bulk sequencing of mRNA and non-coding RNAs), genomic (e.g., integration of single nucleotide variants, insertions/deletions and structural variants from WGS and WES), epigenomic (e.g.,transcription factor, histone and chromatin capture) and other analyses.

Publications

  1. Chromosome 4 Duplication Associated with Strabismus Leads to Gene Expression Changes in iPSC-Derived Cortical Neurons. Genes (Basel). 2025 Jan 12; 16(1). View Abstract
  2. Hospital-wide access to genomic data advanced pediatric rare disease research and clinical outcomes. NPJ Genom Med. 2024 Dec 02; 9(1):60. View Abstract
  3. Genome Sequencing After Exome Sequencing in Pediatric Epilepsy. JAMA Neurol. 2024 Dec 01; 81(12):1316-1318. View Abstract
  4. Utility of Genome Sequencing After Nondiagnostic Exome Sequencing in Unexplained Pediatric Epilepsy. medRxiv. 2024 Aug 09. View Abstract
  5. Cell-type-specific effects of autism-associated 15q duplication syndrome in the human brain. Am J Hum Genet. 2024 Aug 08; 111(8):1544-1558. View Abstract
  6. Mammary adipocytes promote breast tumor cell invasion and angiogenesis in the context of menopause and obesity. Biochim Biophys Acta Mol Basis Dis. 2024 10; 1870(7):167325. View Abstract
  7. Cell-type-specific effects of autism-associated chromosome 15q11.2-13.1 duplications in human brain. bioRxiv. 2024 May 22. View Abstract
  8. Genome-wide analysis of spina bifida risk variants in a case-control study from Bangladesh. Birth Defects Res. 2024 Mar; 116(3):e2331. View Abstract
  9. Zebrafish and cellular models of SELENON-Related Myopathy exhibit novel embryonic and metabolic phenotypes. bioRxiv. 2024 Feb 26. View Abstract
  10. Inflammation drives pathogenesis of early intestinal failure-associated liver disease. Sci Rep. 2024 02 20; 14(1):4240. View Abstract
  11. Heterozygous loss-of-function SMC3 variants are associated with variable growth and developmental features. HGG Adv. 2024 Apr 11; 5(2):100273. View Abstract
  12. Basophils Play a Protective Role in the Recovery of Skin Barrier Function from Mechanical Injury in Mice. J Invest Dermatol. 2024 Aug; 144(8):1784-1797.e4. View Abstract
  13. Heterozygous loss-of-function SMC3 variants are associated with variable and incompletely penetrant growth and developmental features. medRxiv. 2023 Sep 28. View Abstract
  14. Evaluation of the feasibility, diagnostic yield, and clinical utility of rapid genome sequencing in infantile epilepsy (Gene-STEPS): an international, multicentre, pilot cohort study. Lancet Neurol. 2023 09; 22(9):812-825. View Abstract
  15. Toward representative genomic research: the children's rare disease cohorts experience. Ther Adv Rare Dis. 2023 Jan-Dec; 4:26330040231181406. View Abstract
  16. Rethinking Immunological Risk: A Retrospective Cohort Study of Severe SARS-Cov-2 Infections in Individuals With Congenital Immunodeficiencies. J Allergy Clin Immunol Pract. 2023 11; 11(11):3391-3399.e3. View Abstract
  17. Utility of Exome Sequencing for Diagnosis in Unexplained Pediatric-Onset Epilepsy. JAMA Netw Open. 2023 07 03; 6(7):e2324380. View Abstract
  18. Rethinking immunologic risk: a retrospective cohort study of severe SARS-CoV-2 infections in individuals with congenital immunodeficiencies. medRxiv. 2023 Jun 05. View Abstract
  19. Glial dysregulation in the human brain in fragile X-associated tremor/ataxia syndrome. Proc Natl Acad Sci U S A. 2023 06 06; 120(23):e2300052120. View Abstract
  20. Children with Early-Onset Psychosis Have Increased Burden of Rare GRIN2A Variants. Genes (Basel). 2023 03 23; 14(4). View Abstract
  21. The SET oncoprotein promotes estrogen-induced transcription by facilitating establishment of active chromatin. Proc Natl Acad Sci U S A. 2023 02 21; 120(8):e2206878120. View Abstract
  22. Mendelian Disorders in an Interstitial Cystitis/Bladder Pain Syndrome Cohort. Adv Genet (Hoboken). 2023 Mar; 4(1):2200013. View Abstract
  23. Long-Term Characteristics of Human-Derived Biliary Organoids under a Single Continuous Culture Condition. Cells. 2022 Nov 27; 11(23). View Abstract
  24. Clinical Phenotypes and Outcomes in Monogenic Versus Non-monogenic Very Early Onset Inflammatory Bowel Disease. J Crohns Colitis. 2022 Sep 08; 16(9):1380-1396. View Abstract
  25. Single-cell transcriptome profile of mouse skin undergoing antigen-driven allergic inflammation recapitulates findings in atopic dermatitis skin lesions. J Allergy Clin Immunol. 2022 08; 150(2):373-384. View Abstract
  26. Mendelian etiologies identified with whole exome sequencing in cerebral palsy. Ann Clin Transl Neurol. 2022 02; 9(2):193-205. View Abstract
  27. Dual-vector gene therapy restores cochlear amplification and auditory sensitivity in a mouse model of DFNB16 hearing loss. Sci Adv. 2021 Dec 17; 7(51):eabi7629. View Abstract
  28. Evaluation of copy number variants for genetic hearing loss: a review of current approaches and recent findings. Hum Genet. 2022 Apr; 141(3-4):387-400. View Abstract
  29. Congenital X-linked neutropenia with myelodysplasia and somatic tetraploidy due to a germline mutation in SEPT6. Am J Hematol. 2022 01 01; 97(1):18-29. View Abstract
  30. A synonymous coding variant that alters ALAS2 splicing and causes X-linked sideroblastic anemia. Pediatr Blood Cancer. 2022 01; 69(1):e29309. View Abstract
  31. Mechanisms underlying genetic susceptibility to multisystem inflammatory syndrome in children (MIS-C). J Allergy Clin Immunol. 2021 09; 148(3):732-738.e1. View Abstract
  32. A data-driven architecture using natural language processing to improve phenotyping efficiency and accelerate genetic diagnoses of rare disorders. HGG Adv. 2021 Jul; 2(3). View Abstract
  33. Maternal Iron Deficiency Modulates Placental Transcriptome and Proteome in Mid-Gestation of Mouse Pregnancy. J Nutr. 2021 05 11; 151(5):1073-1083. View Abstract
  34. Children's rare disease cohorts: an integrative research and clinical genomics initiative. NPJ Genom Med. 2020; 5:29. View Abstract
  35. Genetic diagnoses in epilepsy: The impact of dynamic exome analysis in a pediatric cohort. Epilepsia. 2020 02; 61(2):249-258. View Abstract
  36. Regulation of the glucocorticoid receptor via a BET-dependent enhancer drives antiandrogen resistance in prostate cancer. Elife. 2017 09 11; 6. View Abstract
  37. Divergence and rewiring of regulatory networks for neural development between human and other species. Neurogenesis (Austin). 2016; 3(1):e1231495. View Abstract
  38. Pax6 associates with H3K4-specific histone methyltransferases Mll1, Mll2, and Set1a and regulates H3K4 methylation at promoters and enhancers. Epigenetics Chromatin. 2016; 9(1):37. View Abstract
  39. Epigenetic Perturbations by Arg882-Mutated DNMT3A Potentiate Aberrant Stem Cell Gene-Expression Program and Acute Leukemia Development. Cancer Cell. 2016 07 11; 30(1):92-107. View Abstract
  40. Chromatin features, RNA polymerase II and the comparative expression of lens genes encoding crystallins, transcription factors, and autophagy mediators. Mol Vis. 2015; 21:955-73. View Abstract
  41. Identification of in vivo DNA-binding mechanisms of Pax6 and reconstruction of Pax6-dependent gene regulatory networks during forebrain and lens development. Nucleic Acids Res. 2015 Aug 18; 43(14):6827-46. View Abstract
  42. Significant expansion of the REST/NRSF cistrome in human versus mouse embryonic stem cells: potential implications for neural development. Nucleic Acids Res. 2015 Jul 13; 43(12):5730-43. View Abstract
  43. Pioneer factors govern super-enhancer dynamics in stem cell plasticity and lineage choice. Nature. 2015 May 21; 521(7552):366-70. View Abstract
  44. Selective inhibition of EZH2 and EZH1 enzymatic activity by a small molecule suppresses MLL-rearranged leukemia. Blood. 2015 Jan 08; 125(2):346-57. View Abstract
  45. Comparison of REST cistromes across human cell types reveals common and context-specific functions. PLoS Comput Biol. 2014 Jun; 10(6):e1003671. View Abstract
  46. Characterization of human pseudogene-derived non-coding RNAs for functional potential. PLoS One. 2014; 9(4):e93972. View Abstract
  47. ETS factors reprogram the androgen receptor cistrome and prime prostate tumorigenesis in response to PTEN loss. Nat Med. 2013 Aug; 19(8):1023-9. View Abstract
  48. An H3K36 methylation-engaging Tudor motif of polycomb-like proteins mediates PRC2 complex targeting. Mol Cell. 2013 Feb 07; 49(3):571-82. View Abstract
  49. Development of patient-specific neurons in schizophrenia using induced pluripotent stem cells. J Neurogenet. 2011 Oct; 25(3):88-103. View Abstract

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