B.S., Bowling Green State University, 1975
Ph.D., University of Maryland, 1983
Postdoc, The Johns Hopkins University, 1985
Down syndrome (DS) occurs as a result of Trisomy 21 (Ts21) and is among the most complicated genetic conditions compatible with human survival. Our goal is to understand how gene dosage imbalance disrupts development in DS in order to develop and test potential therapies for DS features. The lab studies multiple aspects of the many phenotypes that result from Ts21, including studies in human populations and in mouse and other model systems. We use chromosome engineering in ES cells, creating defined dosage imbalance in mice to localize the genes contributing to trisomic features and to test directly hypotheses concerning DS "critical regions" on human chromosome 21. Quantitative phenotypic assays that we have developed give a precise and sensitive readout of the relative effects on phenotype when overlapping subsets of genes are at dosage imbalance. Developmental analyses of these traits are underway to identify the timing and location of divergence between trisomic and euploid fetuses. Among our recent findings are validation of epidemiological findings suggesting a lower incidence of cancer in DS and identification of a genes that plays a key role in tumor resistance; determination that a deficit in cranial neural crest is the (initial) basis for the hypomorphic craniofacial skeleton that produces the characteristic appearance of individuals with DS; and discovered the basis for and a “treatment” of a fundamental neuronal deficit in the trisomic brain. Definition of the timing and location of malformations, and of the gene(s) primarily contributing to them, forms the basis for genetic, pharmacologic and stem cell therapies to ameliorate these anomalies. In a multi-Institute collaboration we have combined genetic analysis of patient samples, candidate gene sequencing and mouse modeling to identify modifiers producing congenital heart disease in human beings based on the 2000x elevation of this trait in DS. CHD is the most frequent birth defect in human beings regardless of ploidy. This recruitment network is now being used to support collection of cognitive phenotypes in patient populations to characterize the range of cognitive dysfunction in DS; to provide a readout for future therapeutic trials; and to establish a network that would ultimately support a clinical trials program.
- Preceptor/other: 1) Cell and Molecular Physiology - Graduate Advisory Committee (94-96), Curriculum and Rotations Committee, (00- ); 2) Biochemistry, Cell, and Molecular Biology - Policy (90-00), Admissions (88-90) committees; 3) Cell and Molecular Medicine, Policy Committee (04- ); 4) Predoctoral Training Program in Human Genetics - Curriculum, Admissions, Executive committees (91- ).
- Visiting Scientists/ Mentorships (5 since 1993); Post-doctoral fellows (12 since 1988 including 1 current); Graduate students (18 since 1987 including 5 current)
- Teaching: Lecturer, "Comparative phenotyping," Div. Comp. Med.; "BioInformatics for comparative genome analysis," HumGen; "The Human Genome," Bloomberg SPH; “Hematopoiesis” and “Neural Crest”, Medical Developmental Biology, JHUSOM; "Mammalian Genetics," BCMB Core Course, Fundamentals of Genetics; Co-director, Advanced Topics in Human Genetics, HumGen/CMM; Instructor/Director, Cold Spring Harbor Laboratory Course, "Positional Cloning: Contig to Candidate Gene," (1995-97)
- Theodore D. Tjossem Research Award, National Down Syndrome Congress (2008)
- Inaugural address, National Down Syndrome Society Educational Series (2008)
- Terence R. Doland Lecture, The Waisman Center, University of Wisconsin (2008)
- Director, Summer Internship Diversity Program (91-05);
- Director, Post-Baccalaureate Research and Education Program (04 - )
- Editorial Boards, Genomics, Journal of Heredity, Mammalian Genome, Genome Research (95-04), Cancer Genomics and Proteomics, Journal of Neurodevelopmental Disorders
- Past Advisory Boards: Mouse Genome Database (98-01); Rat Genome Database (00-02); Biology and Biotechnology Resource Program, Lawrence Livermore National Laboratory (98-00)
- Faculty Director, JHUSOM Transgenic Core Facility; Chairman, JHUSOM Rodent Advisory Committee
- Genome Research Review Committee (NHGRI), Developmental Biology Review Group (NICHD), multiple NIH and other study sections
- Reeves, R.H., N.G. Irving, T. Moran, A. Wohn, C. Kitt, S. Sisodia, C. Schmidt, R.T. Bronson and M.T. Davisson. 1995. A mouse model for Down Syndrome exhibits learning and behavior deficits. Nature Genetics 11:177-184.
- Reeves RH: Recounting a genetic story. Nature 405:283-284, 2000. Abstract
- Richtsmeier JT, Baxter LL, Reeves RH: Parallels of craniofacial development in Down syndrome and Ts65Dn mice. Dev Dyn 217:137-145, 2000. Abstract
- Kuramochi M, Fukuhara H, Nobukuni T, Kanbe T, Maruyama T, Ghosh HP, Pletcher M, Isomura M, Onizuka M, Kitamura T, Sekiya T, Reeves RH, Murakami Y: TSLC1 is a tumor suppressor gene in human non-small cell lung cancer. Nat Genet 27:427-430, 2001.
- Reeves RH, Baxter LL, Richtsmeier JT: Too much of a good thing: Mechanisms of gene action in Down syndrome. Trends Genet 17:83-88, 2001. Abstract
- Olson L.E., J.T. Richtsmeier, J. Leszl, and R.H. Reeves. 2004. Direct testing does not support a Chromosome 21 Critical Region as the cause of Down syndrome phenotypes when triplicated. Science 306:687-690.
- Roper, R.J.*, L.L. Baxter*, N. Saran, D. Klinedinst, P. Beachy and R.H. Reeves. 2006. Defective cerebellar response to mitogenic Hedgehog signaling in Down syndrome mice. Proc. Natl. Acad. Sci. 103(5):1452-6. *These authors contributed equally.
- Roper, R.J. and R.H. Reeves. 2006. Understanding the Basis for Down Syndrome Phenotypes. 2006. PLoS Genetics 2:e50.
- Sussan T., A. Yang. F. Li, M. Ostrowski and R.H. Reeves. 2008. Trisomy protects against ApcMin-mediated tumors in mouse models of Down syndrome. Nature 451:73-5.
Roger Harper Reeves, Ph.D.
Department of Physiology, P202
Johns Hopkins University School of Medicine
725 N. Wolfe Street
Baltimore, MD 21205
Phone: (410) 955-6621
Fax: (443) 287-0508