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Andrew S. McCallion, Ph.D.

Assistant Director, Human Genetics Graduate Program
Associate Professor of Molecular and Comparative Pathobiology

Titles

  • Assistant Director, Human Genetics Graduate Program
  • Associate Professor of Molecular and Comparative Pathobiology
  • Associate Professor of Medicine
  • Associate Professor of Pediatrics

Centers & Institutes

Departments

Contact for Research Inquiries

Johns Hopkins University

733 N. Broadway
Institute for Genetic Medicine
Baltimore, MD 21205 map

Research Interests

Genetics basis of congenital malformations; Genetics of neurological, neuropsychiatric and neural-crest disorders; Transcriptional regulation in development and disease

Biography

Dr. Andrew McCallion is an associate professor of molecular and comparative pathobiology at the Johns Hopkins University School of Medicine. His research focuses on applying functional genetics to human development and disease. Dr. McCallion was part of a research team at Johns Hopkins that identified the two genes that cause Hirschsprung disease, an inherited intestinal disorder.

His research focuses on making the connection between gene sequence (and variation therein) and phenotype through the integrated use of contemporary genomic strategies and model systems (mouse, zebrafish and cell culture).

Dr. McCallion received his B.Sc. in genetics from The Queen's University of Belfast. He earned his Ph.D. in genetics from the University of Glasgow. He completed postdoctoral training at Case Western Reserve University Medical School.

Prior to joining Johns Hopkins, Dr. McCallion was a project leader and staff scientist at Neuropa Ltd. (UK), a biotech startup focused on drug target development for neurodegenerative disorders.

He is a member of the International Mammalian Genome Society, American Society of Human Genetics and Federation of American Societies for Experimental Biology. He serves on the editorial board of Genome Research, and is a Faculty of 1000 faculty member in genomics and genetics.

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    Additional Information

  • Education +
  • Research & Publications +

    Research Summary

    Dr. McCallion's research focuses on the roles played by cis-regulatory elements (REs) in controlling the timing, location and levels of gene activation (transcription). However, the biological relevance of non-coding sequences cannot be inferred by examination of sequence alone. Perhaps the most commonly used indicator of non-coding REs is evolutionary sequence conservation. Although conservation can uncover functionally constrained sequences, it cannot predict biological function, and regulatory function is not always confined to conserved sequences. At its simplest level, regulatory instructions are inscribed in transcription factor binding sites (TFBS) within REs. Yet, while many TFBS have been identified, TFBS combinations predictive of specific regulatory control have not yet emerged for vertebrates. Dr. McCallion and his team posit that motif combinations accounting for tissue-specific regulatory control can be identified in REs of genes expressed in those cell types. Their immediate goal is to begin to identify TFBS combinations that can predict REs with cell-specific biological control—a first step in developing true regulatory lexicons.

    Lab:

    Gene regulation is the framework on which vertebrate cellular diversity is built. The substantial cellular diversity that characterizes complex integrated cell populations, such as the human central nervous system, must therefore require immense regulatory complexity. Similarly, the cells comprising the embryonic neural crest, a population that contributes craniofacial cartilage and bone, pigment cells of the skin and hair, neuroendocrine cells and the entire peripheral nervous system to the vertebrate embryo, must face similar challenges in choosing the correct fate. These cells go awry in a wide array of human disorders like Parkinson's disease, Hirschsprung disease, psychiatric disorders and melanoma, and comprise the focus of our efforts.

    Although regulatory control acts at many levels, we focus on the roles played by cis-regulatory elements (REs) in controlling the timing, location and levels of gene activation (transcription). However, the biological relevance of non-coding sequences cannot be inferred by examination of sequence alone. Perhaps the most commonly used indicator of non-coding REs is evolutionary sequence conservation. Although conservation can uncover functionally constrained sequences, it cannot predict biological function, and regulatory function is not always confined to conserved sequences. At its simplest level, regulatory instructions are inscribed in transcription factor binding sites (TFBS) within REs. Yet, while many TFBS have been identified, TFBS combinations predictive of specific regulatory control have not yet emerged for vertebrates. We posit that motif combinations accounting for tissue-specific regulatory control can be identified in REs of genes expressed in those cell types. Our immediate goal is to begin to identify TFBS combinations that can predict REs with cell-specific biological control—a first step in developing true regulatory lexicons.

    As a functional genetic laboratory, we develop and implement assays to rapidly determine the biological relevance of sequence elements within the human genome and the pathological relevance of variation therein. In recent years, we have developed a highly efficient reporter transgene system in zebrafish that can accurately evaluate the regulatory control of mammalian sequences, enabling characterization of reporter expression during development at a fraction of the cost of similar analyses in mice. We employ a range of strategies in model systems (zebrafish and mice), as well as analyses in the human population, to illuminate the genetic basis of disease processes. Our long-term objective is to use these approaches in contributing to improved diagnostic, prognostic and ultimately therapeutic strategies in patient care.

    If you are interested in learning more about the work we do or would like to inquire about positions available within the lab, please contact Dr. McCallion (andy@jhmi.edu).

    Lab Website: Andrew McCallion Laboratory

    CORE Facilities

    Phenotyping (and Pathology) Core (Phenocore)

    Selected Publications View all on PubMed

    Maragh S, Miller RA, Bessling SL, McGaughey DM, Wessels MW, de Graaf B, Stone EA, Bertoli-Avella AM, Gearhart JD, Fisher S, McCallion AS. "Identification of RNA binding motif proteins essential for cardiovascular development." BMC Dev Biol. 2011 Oct 19;11:62. doi: 10.1186/1471-213X-11-62.

    Stine ZE, McGaughey DM, Bessling SL, Li S, McCallion AS. "Steroid hormone modulation of RET through two estrogen responsive enhancers in breast cancer." Hum Mol Genet. 2011 Oct 1;20(19):3746-56. doi: 10.1093/hmg/ddr291. Epub 2011 Jul 7.

    Taher L, McGaughey DM, Maragh S, Aneas I, Bessling SL, Miller W, Nobrega MA, McCallion AS, Ovcharenko I. "Genome-wide identification of conserved regulatory function in diverged sequences." Genome Res. 2011 Jul;21(7):1139-49. doi: 10.1101/gr.119016.110. Epub 2011 May 31.

    Antonellis A, Dennis MY, Burzynski G, Huynh J, Maduro V, Hodonsky CJ, Khajavi M, Szigeti K, Mukkamala S, Bessling SL, Pavan WJ, McCallion AS, Lupski JR, Green ED; NISC Comparative Sequencing Program. "A rare myelin protein zero (MPZ) variant alters enhancer activity in vitro and in vivo." PLoS One. 2010 Dec 16;5(12):e14346. doi: 10.1371/journal.pone.0014346.

    Noonan JP, McCallion AS. "Genomics of long-range regulatory elements." Annu Rev Genomics Hum Genet. 2010;11:1-23. doi: 10.1146/annurev-genom-082509-141651. Review.

  • Academic Affiliations & Courses +

    Graduate Program Affiliation

    Preceptor-Predoctoral Training Program in Human Genetics

    Courses and Syllabi

    Molecular Mechanisms of Disease (Director) (ME 710.702)

    Advanced Topics in Human Genetics (Lecturer) (ME 710.700)

    Phenotyping for Functional Genetics (Lecturer) (ME 680.712)

    Short Course in Medical and Experimental Mammalian Genetics (Lecturer)

  • Activities & Honors +

    Honors

    • Faculty of 1000, Genomics and Genetics

    Memberships

    • American Society of Human Genetics
      Member
    • Federation of American Societies for Experimental Biology
      Member
    • International Mammalian Genome Society
      Member

    Professional Activities

    • Rodent Advisory Committee, Johns Hopkins University
    • Rodent Phenotyping CORE committee, Johns Hopkins University
    • Editorial board, Genome Research, 2006
  • Videos & Media +
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