Andrew S. McCallion, Ph.D. Assistant Professor, Department of Molecular |  |
Education and Training:
- B.Sc.(Hons), The Queen's University of Belfast, Genetics, 1990-94
- Ph.D., University of Glasgow, Genetics, 1994-97
- Project leader and staff scientist, Neuropa Ltd, Glasgow, 1997-99
- Research Associate, Department of Genetics, Case Western Reserve University Medical School, 1999-2000
- Research Associate, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University Medical School, 2000-2003
Main Interests:
The capacity to predict the functional consequence of any sequence variation in a given coding (or non-coding) sequence represents the Holy Grail in genetics. There is clearly a need to more rapidly connect the DNA sequence (genotype) with clinical presentation (phenotype) and ultimately to improve therapeutics and clinical care. It is thereforecritical to be able to discriminate between functional and non-functional sequence and the variants therein. Importantly, mutations in regulatory sequences (promoters, enhancers, silencers etc.) influence the tissue specificity, timing and/or level of the corresponding gene product and are predicted to play a significant role in inherited human disease. However, unlike coding sequences, the nature and identity of regulatory mutations have not yet been established. Our research combines comparative sequence analysis with transgenic paradigms, in multiple vertebrate organisms (mouse and zebrafish), to rigorously assess the correlation between conservation and functional constraint in non-coding sequences. Our aim is to uncover the nature and identity of regulatory sequences in critical developmental or disease genes and the variants that may compromise them. We focus our efforts on understanding the role these mutations play in congenital abnormalities (Hirschsprung disease, Campomelic dysplasia), defects of the nervous system (Parkinson disease, Hirschsprung disease), heart disease and cancer (Multiple Endocrine Neoplasia type 2). Our long-term objective is to develop functional approaches to individualized medicine for inherited diseases through the dissection of disease mechanisms and the development of therapeutic screens.
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). If you would like to support our efforts please contact the Insitute at "Join Our Team".
Research Interests:
- Gene regulation in development and disease
- Comparative functional genomics
- Molecular basis of non-Mendelian disease
- Synthesizing human phenotypes in vertebrate models
Educational Activities:
- Preceptor-Predoctoral Training Program in Human Genetics
Recognition and Leadership Roles:
- Faculty of 1000, Genomics and Genetics
- Editorial board, GENOME RESEARCH 2006 -
- Member, International Mammalian Genome Society
- Member, American Society of Human Genetics
- Member, Federation of American Societies for Experimental Biology
- Rodent Advisory Committee, Johns Hopkins University
- Rodent Phenotyping CORE committee, Johns Hopkins University
Selected Publications:
Antonellis A., Huynh, J., Lee-Lin, S., Vinton, RM., Renaud, G., Loftus, SK., Elliot, Wolfsberg, TG., Green, ED., McCallion, A.S.,ð and Pavan W.J. Identification Of Neural Crest And Glial Enhancers At The Mouse Sox10 Locus Through Transgenesis In Zebrafish. PLoS Genet. 2008, 4; 9. (ð, Corresponding author)
Miller RA, Christoforou N, Pevsner J, McCallion AS*, Gearhart JD* (2008) Efficient Array-Based Identification of Novel Cardiac Genes through Differentiation of Mouse ESCs. PLoS ONE 3(5): e2176 doi:10.1371/journal.pone.0002176; *, corresponding authors.
Christoforou, N.,* Miller, R.A.,* Hill, C.M., Jie, C.C., McCallion, A.S., and Gearhart. J.D. The characterization of ES-derived cardiac precursor cells demonstrates their class multipotentiality and identifies novel cardiac genes. J. Clin. Invest. Feb. 2008.
McGaughey, D.M., Vinton, R.M., Huynh, J., Al-Saif, A., Beer, M., and McCallion, A.S. Metrics of sequence constraint overlook regulatory sequences in an exhaustive analysis at phox2b. Genome Research, In press.
Fisher, S., Grice, E.A., Vinton, R.., Bessling, S.L., Urasaki, A., Kawakami, K. and McCallion, A.S. (2006) Evaluating the biological relevance of putative enhancers using Tol2 transposon-mediated transgenesis in zebrafish. Nature protocols 1, 1297-1305.
Cranston, A.N., Carniti, C., Oakhill, K., Radzio-Andzelm, E., Stone, E.A., McCallion, A.S., Hodgson, S., Clarke, S., Mondellini, P., Leyland, J., Pierotti, M.A., Whittaker, J., Taylor, S.S., Bongarzone, I. & Ponder, B.A.J. (2006) RET is constitutively activated by novel tandem substitutions that alter the active site resulting in MEN2B. Cancer Research 66(20):10179-87.
Montague, P., McCallion, A.S., Davies, R.W., and Griffiths, I.R. (2006) Myelin-associated oligodendrocytic basic protein: a family of abundant CNS myelin proteins in search of a function. Dev Neurosci. 28(6):479-87.
Fisher S, Grice EA, Vinton RM, Bessling SL and McCallion AS. (2006) Conservation of RET Regulatory Function from Human to Zebrafish Without Sequence Similarity. Science. 2006 Mar 23; [Epub ahead of print]
Grice EA, Rochelle ES, Green ED, Chakravarti A, McCallion AS. (2005) Evaluation of the RET regulatory landscape reveals the biological relevance of a HSCR-implicated enhancer. Hum Mol Genet. 14 (24)
Kashuk, C.S., Stone, A.E., Grice, E.A., Portnoy, M.E., Green, E.D., Sidow, A., Chakravarti, A. and McCallion, A.S. (2005) Phenotype:Genotype correlation in HSCR and MEN2 facilitated comparative analysis of the RET protein sequence. Proceedings of the National Academy of Science (USA) 102: 8949-8954.
Sproat-Emison, E.E.,* McCallion, A.S.,* Kashuk, C.S., Bush, R.T., Grice, E., Lin, S., Portnoy, M.E., NISC Comparative Sequencing Program, Cutler, D.J., Green, E.D. and Chakravarti, A. (2005) A common, sex-dependent mutation in a putative RET enhancer underlies Hirschsprung disease susceptibility. Nature, 434 (7035): 857-63. (*, Authors contributed equally).
Montague P, McCallion AS, Barrie JE, Edgar JM, Davies RW and Griffiths IR (2005): Characterization of the murine splice variant Mobp155: developmental CNS expression pattern and subcellular localization of epitope-tagged protein. Glia, 50, 80-85.
McCallion, A.S., Sproat-Emison, E.E., Kashuk, C.S. Bush, R.T., Kenton, M. Carrasquillo, M.M., Jones, K.W., Kennedy, G.C., Portnoy, M., Green, E.D., and Chakravarti, A (2003) Genome-wide association study and mouse model identity interaction between RET nad EDNRB pathways in Hirschsprung disease. Cold Spring Harb Symp Quant Biol. LXVII
McCallion, A.S., Stames, E, Conlon, R.A., and Chakravarti, A. (2003) Phenotype variation in two-locus mouse models of Hirschsprung disease: Tissue specific interaction between and ., 1826-31. Ret and Ednrb. PNAS 100, 1826-31.
Carrasquillo, M.M., McCallion, A.S., Puffenberger, E.P., Kashuk, C.S. Nouri, N. and Chakravarti, A. (2002) Genome-wide association study and mouse model identify interaction between RET and EDNRB pathways in Hirschsprung disease. Nat Genet 32,237-244.
Yool, D., Montague, P., McLaughlin, M., McCulloch, M.C., Nave K-A., Davies R.W. and McCallion, A.S. (2002) Phenotypic analysis of mice deficient in the major myelin protein MOBP, and evidence for a novel Mobp isoform. Glia, 39 (3): 254-265.
Book Chapters
Chakravarti, A., McCallion, A.S. and Lyonnet, S. (2000, revised 2003). Hirschsprung Disease. Chapter 251 in, The metabolic and molecular bases of inherited disease. Scriver, Beaudet, Valle and Sly; 8th edition, McGraw-Hill, New York.
McCallion, A.S., Chakravarti, A. (2004) RET, Hirschsprung disease and multiple endocrine neoplasia type 2. In Inborn Errors of Development. Editors Epstein, C., Erickson, R., and Wynshaw-Boris, A. Oxford University Press (San Francisco) References
Contact:
Andrew McCallion, PhD McKusick-Nathans |
Xie J, Bessling SL, Cooper TK, Dietz HC, McCallion AS, Fisher S. Manipulating Mitotic Recombination in the Zebrafish Embryo Through RecQ Helicases. Genetics. 2007 Jun;176(2):1339-42.
