Roger Harper Reeves, Ph.D

Roger Harper Reeves, Ph.D.

Main Interests:

Down syndrome (DS) occurs as a result of Trisomy 21 and is among the most complicated genetic conditions compatible with human survival. My laboratory creates and characterizes mouse models to understand why and how gene dosage imbalance disrupts development in DS. We use chromosome engineering in ES cells to create defined dosage imbalance in order to localize the genes contributing to these anomalies 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. These have validated epidemiological findings suggesting a lower incidence of cancer in DS and substantially narrowed the number of candidate genes; established a deficit in cranial neural crest as the (initial) basis for the hypomorphic craniofacial skeleton that produces the characteristic appearance of individuals with DS; and led to the recent discovery of the basis for and “treatment” of a fundamental structural deficit in the trisomic brain. Definition of the timing and location of malformations, and of the gene(s) primarily contributing, forms the basis for genetic, pharmacologic and stem cell therapies to ameliorate these anomalies (see Trends in Genetics 17:83-88, 2001). 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.

 Research Interests:

• Mechanisms of gene action in Down syndrome
• Quantitative trait loci in the inflammatory response
• Link:   Reeves Laboratory

 Educational Activities:

• 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 Physiology (04- ); 4) Predoctoral Training Program in Human Genetics - Curriculum, Admissions, Executive committees (91- );
  Visiting Scientists/ Mentorships (5 since 1993); Post-doctoral fellows (11 since 1988); Graduate students (15 since 1987; 12 completed, 3 in progress)
• 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) 

 Recognition and Leadership Roles:

• Director, Summer Internship Diversity Program;
• Director, Post-Baccalaureate Research and Education Program
• Editorial Boards, Genomics, Journal of Heredity, Mammalian Genome, Cancer Genomics and Proteomics
• 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) and other NIH study sections 

 Publications:

• 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.

 Contact Information:

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
E-Mail: rreeves@jhmi.edu