David Valle, M.D.

Henry J. Knott Professor and Director of the Institute of Genetic Medicine Professor, Departments of Pediatrics, Ophthalmology and Molecular Biology & Genetics

Education:

• 1965, B.S., Duke University
• 1969, M.D., Duke University
• 1975, Pediatric Residency, Johns Hopkins University

Main Interests:

In the broadest sense, my research interests include understanding all aspects of the role of genetic factors in human health and disease.  In particular, our studies involve clinical, biochemical, molecular and therapeutic aspects of specific human genetic diseases as well as more global studies of the network interactions and consequences of the genes and proteins implicated in human disease.

In the past, our lab has focused primarily on rare monogenic disorders including inborn errors of amino acid metabolism as well as various human retinal degenerations.  For example, we have conducted extensive molecular, biochemical and structural studies of the enzymes of proline and ornithine metabolism defining the biochemical and molecular bases of several.  Most notably, we showed that deficiency of ornithine-delta-aminotransferase (OAT) causes a blinding, chorioretinal degeneration known as gyrate atrophy of the choroid and retina (GA).  We also produced a knockout mouse deficient in OAT, showed that it develops a retinal degeneration and used this model to develop and validate treatments.  Similarly, we are interested in inborn errors of biogenesis and function of the peroxisome, a ubiquitous sub-cellular organelle whose protein components participate in numerous metabolic pathways.  Using a variety of strategies, we identified the genes responsible for several (>10) genetic disorders of peroxisomal biogenesis (e.g. Zellweger syndrome).  We also have a special interest in peroxisomal ABC transporters and have produced knockout mice for the genes encoding some of these to elucidate the function of these transporters and their role in human genetic disease.

Recently, we have focused most of our efforts on understanding the genetic contribution to neuropsychiatric disease, especially schizophrenia.  Working together with our collaborators Ann Pulver, Dimitri Avramopoulos and Gerry Nestadt, we have utilized a variety of whole genome approaches to search for genetic variants contributing risk for these disorders.  Currently we are performing extensive studies of the genes in 10q22-23 and 8p21; we have found both linkage and association evidence for one or more schizophrenia susceptibility genes in both these regions.  Our studies include extensive high throughput genotyping and sequencing, functional evaluation of coding variants and variants in candidate regulatory sequences and development and characterization of mouse models for the strongest candidates.  The overall all goals of these studies are to identify the genes and the causative variants contributing risk and to use this information to identify key biological systems involved in the causation and pathophysiology of these disorders.  We will use this information to search for additional risk genes and environmental variables as well as for the rational development of therapies.

Research Interests:

• Clinical, biochemical, and molecular bases of disease
• Genetic factors in neuropsychiatric disease
• Inborn errors of metabolism
• Education
• Medical sequencing, genome sequencing and comparative genomics
• Links:
  Center for Inherited Disease Research (CIDR)
  Online Mendelian Inheritance in Man (OMIM)

 Clinical Activities:

• Board Certification:
  1977 Pediatric Board Certification
  1982 Clinical Genetics, American Board of Medical Genetics
  1982 Clinical Biochemical Genetics, American Board of Medical Genetics
  1993 Clinical Molecular Genetics, American Board of Medical Genetics
• Clinic:
  Medical Genetics Clinic Johns Hopkins
  Phone: 410-955-3071 Fax: 410-614-9246 

Educational Activities:

• Director, Predoctoral Training Program in Human Genetics
• Co-Director, Genes to Society (1^st & 2^nd year medical school)
• Courses taught: Co-Director of the Annual Short Course in Medical and Experimental Mammalian Genetics, The Jackson Laboratory, Bar Harbor, Maine; Molecules and Cells (1st year medical school); Human Genetics (1st year graduate school)
• Textbook: Scriver's Metabolic and Molecular Bases of Inherited Disease Valle D, Beaudet AR, Sly W (eds)

Recognition and Leadership Roles:

• Member, Large Scale Sequencing Committee, NHGRI
• Member, Institute of Medicine of the National Academy of Sciences
• Fellow, American Association for the Advancement of Science
• Member, Large Scale Sequencing Advisory Committee, NHGRI
• Past-President, American Society of Human Genetics
• Professional society memberships and other professional affiliations:
• American Society of Human Genetics
• Society for Inherited Metabolic Disorders
• Society for the Study of Inborn Errors of Metabolism
• Society for Pediatric Research
• American Society of Clinical Investigation
• American Federation for Clinical Research
• Genetics Society of America
• Human Genome Organization
• European Society of Human Genetics
• American College of Medical Genetics
• American Pediatrics Society

Selected Publications:

• • Mulle JG, Dodd AF, McGrath JA, Wolyniec PS, Mitchell AA, Shetty AC, Sobreira NL, Valle D, Rudd MK, Satten G, Cutler DJ, Pulver AE, Warren ST. Microdeletions of 3q29 confer high risk for schizophrenia. Am J Hum Genet. 2010 Aug 13;87(2):229-36.PMID: 20691406 <http://www.ncbi.nlm.nih.gov/pubmed/20691406>
    
    
  • Huang CR, Schneider AM, Lu Y, Niranjan T, Shen P, Robinson MA, Steranka JP, Valle D, Civin CI, Wang T, Wheelan SJ, Ji H, Boeke JD, Burns KH. Mobile interspersed repeats are major structural variants in the human genome. Cell. 2010 Jun 25;141(7):1171-82.PMID:
    20602999<http://www.ncbi.nlm.nih.gov/pubmed/20602999>
    
    
  • Sobreira NL, Cirulli ET, Avramopoulos D, Wohler E, Oswald GL, Stevens EL, Ge D, Shianna KV, Smith JP, Maia JM, Gumbs CE, Pevsner J, Thomas G, Valle D, Hoover-Fong JE, Goldstein DBWhole-genome sequencing of a single proband together with linkage analysis identifies a Mendelian disease gene.
    .PLoS Genet. 2010 Jun 17;6(6):e1000991.PMID: 20577567 <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2887469/?tool=pubmed>
    
    
  • Guilmatre A, Legallic S, Steel G, Willis A, Di Rosa G, Goldenberg A, Drouin-Garraud V, Guet A, Mignot C, Des Portes V, Valayannopoulos V, Van Maldergem L, Hoffman JD, Izzi C, Espil-Taris C, Orcesi S, Bonafé L, Le Galloudec E, Maurey H, Ioos C, Afenjar A, Blanchet P, Echenne B, Roubertie A, Frebourg T, Valle D, Campion D. Type I hyperprolinemia: genotype/phenotype correlations. Hum Mutat. 2010 Aug;31(8):961-5. PMID: 20524212  <http://www.ncbi.nlm.nih.gov/pubmed/20524212>
    
    
  • Liu Y, Chen PL, McGrath J, Wolyniec P, Fallin D, Nestadt G, Liang KY, Pulver A, Valle D, Avramopoulos D. Replication of an association of a common variant in the Reelin gene (RELN) with schizophrenia in Ashkenazi Jewish women. Psychiatr Genet. 2010 Aug;20(4):184-6.PMID: 20431428 [PubMed - in process]<http://www.ncbi.nlm.nih.gov/pubmed/20431428>
    
    
  • Tan B, Brown D, Xu S, Valle D. PHR1 is a vesicle-bound protein abundantly expressed in mature olfactory neurons. Laryngoscope. 2010 May;120(5):1002-10.PMID: 20301200<http://www.ncbi.nlm.nih.gov/pubmed/20301200>
    
    
  • miRNA mutations are not a common cause of deafness. Hildebrand MS, Witmer PD, Xu S, Newton SS, Kahrizi K, Najmabadi H, Valle D, Smith RJ. Am J Med Genet A. 2010 Mar;152A(3):646-52.PMID: 20186779 <http://www.ncbi.nlm.nih.gov/pubmed/20186779>
    
    
  • Wiener CM, Thomas PA, Goodspeed E, Valle D, Nichols DG.
    "Genes to society"--the logic and process of the new curriculum for the Johns Hopkins University School of Medicine. Acad Med. 2010 Mar;85(3):498-506. PMID: 20182127
    <http://www.ncbi.nlm.nih.gov/pubmed/20182127>
    
    
  • Nesse RM, Bergstrom CT, Ellison PT, Flier JS, Gluckman P, Govindaraju DR, Niethammer D, Omenn GS, Perlman RL, Schwartz MD, Thomas MG, Stearns SC, Valle D. Evolution in health and medicine Sackler colloquium: Making evolutionary biology a basic science for medicine. Proc Natl Acad Sci U S A. 2010 Jan 26;107 Suppl 1:1800-7.  Epub 2009 Nov 16.PMID: 19918069
    <http://www.ncbi.nlm.nih.gov/pubmed/19918069>

Textbooks:

• Scriver's Metabolic and Molecular Bases of Inherited Disease Valle D, Beaudet AR, Sly W (eds)

Books Chapters:

• Phang JM, Hu C-A, Valle D: Disorders of proline and hydroxyproline metabolism. In The Metabolic and Molecular Bases of Inherited Disease, 8th ed. Scriver CR, Beaudet AR, Sly W, Valle D (eds), McGraw-Hill, New York, pp 1821-1838, 2001.
• Beaudet AL, Scriver CR, Sly WS, Valle D: Genetics, biochemistry and molecular basis of variant human phenotypes. In The Metabolic and Molecular Bases of Inherited Disease, 8th ed. Scriver CR, Beaudet AR, Sly W, Valle D (eds), McGraw-Hill, New York, pp 3-45, 2001.
• Jimenez-Sanchez G, Childs B, Valle D: The effect of Mendelian disease on human health. In The Metabolic and Molecular Bases of Inherited Disease, 8th ed. Scriver CR, Beaudet AR, Sly W, Valle D (eds), McGraw-Hill, New York, pp 167-174, 2001.
• Valle D, Simell O: The hyperornithinemias. In The Metabolic and Molecular Bases of Inherited Disease, 8th ed. Scriver CR, Beaudet AR, Sly W, Valle D (eds), McGraw-Hill, New York, pp 1857-1896, 2001.
• Childs B, Valle D, Jimenez-Sanchez G: The inborn error and biochemical individuality. In The Metabolic and Molecular Bases of Inherited Disease, 8th ed. Scriver CR, Beaudet AR, Sly W, Valle D (eds), McGraw-Hill, New York, pp 155-166, 2001.
• Gould SJ, Raymond G, Valle D: The peroxisome biogenesis disorders. In The Metabolic and Molecular Bases of Inherited Disease, 8th ed. Scriver CR, Beaudet AR, Sly W, Valle D (eds), McGraw-Hill, New York, pp 3181-3218, 2001.
• Treacy EP, Valle D, Scriver CR: Treatment of genetic disease. In The Metabolic and Molecular Bases of Inherited Disease, 8th ed. Scriver CR, Beaudet AR, Sly W, Valle D (eds), McGraw-Hill, New York, pp 175-192, 2001. 

Contact Information:

David Valle, M.D.
Assistant:  Sandy Muscelli


Johns Hopkins University School of Medicine
Institute of Genetic Medicine
733 N Broadway
Broadway Research Building, 519
Baltimore, MD  21287
Phone: 410-955-4260
Fax: 410-955-7397
E-Mail: dvalle@jhmi.edu