Professor of Pediatrics
University of Texas Houston Medical Center
Phone: 713-500-5763
E-mail: Jacqueline.T.Hecht@uth.tmc.edu
http:/gsbs.gs.uth.tmc.edu/tutorial/hecht.html
The goal of our Hereditary Multiple Exostoses research has been to understand how and why the exostoses develop. Mutations in either EXT1 or EXT2 genes are the cause of the HME, but how mutations affect chondrocyte development and function is unknown. Our studies focus on the exostoses chondrocytes that we isolate from the exostoses that are surgically removed from patients age 16 and under.
Associate Professor of Medicine
Department of Medicine
University of Washington
E-mail: wendyrun@washington.edu
Current research involves investigating the kinds of mutations that occur in the EXT 1 and EXT2 genes. Also of interest is the sequence of steps that take place in the progression from normal cells to exostosis to chondrosarcoma. Samples are accepted from patients with MHE and their family members; however, the priority is for individuals with large enough families to determine which of the genes is involved before sequence analysis is done. Of further interest are individuals with or having a family history of chondrosarcoma or osteosarcoma, as well as families having other unusual manifestations, such as early osteoarthrities or osteoporosis.
Professor, Department of Cellular and Molecular Medicine
Associate Director, Glycobiology Research and Training Center
University of California-San Diego
Phone: 858-822-1100
E-mail: jesko@ucsd.edu
Fax: 858-534-5611
http://cmm.ucsd.edu/esko/biography.html
Research in my laboratory focuses on the structure, function, and biosynthesis of glycoproteins and proteoglycans. Glycoproteins and proteoglycans are found on the surface of cells or in the extracellular matrix where they interact with numerous ligands and promote fundamental biological processes such as cell signaling and adhesion. To understand better the biological activity of these molecules, we have identified animal cell mutants defective in proteoglycan biosynthesis and have targeted the corresponding genes in worms and mice. These mutants allow us to study the assembly of proteoglycans in intact cells and in cell extracts, to clone the normal genes that correspond to the mutations, and to analyze the role of proteoglycans in early development.
We also work on the design and synthesis of small molecule inhibitors of glycosylation. One group of compounds consists of synthetic glycosides that stimulate the formation of oligosaccharides by acting as primers, thus mimicking endogenous biosynthetic intermediates. Priming diverts the assembly of polysaccharide chains away from endogenous subtrates, and thus act as inhibitors. These compounds are being tested as anti-inflammatory agents and as inhibitors of tumor cell adhesion and metastasis. In particular we are interested in whether altering the interaction of glycans with selectin receptors affects neutrophil extravasation in the lungs.
Professor, Department of Pediatrics
Genetics, Cell Biology and Development
University of Minnesota
Email: selle011@umn.edu
Professor and Chair
Department of Biology and Biochemistry
Institute for Molecular Biology
University of Houston
Houston, Texas 77204
Voice: 713-743-2671
Fax: 713-743-2636
email: dwells@uh.edu
http://www.bchs.uh.edu/People/Wells/Wells.html
My current research relevant to Hereditary Multiple Exostosis is focused on the EXT 1 gene present on chromosome 8. This research is aimed at understanding the molecular, genetic and functional basis of HME and the role mutations in the EXT 1 gene play in this condition. Recently, my laboratory has developed a mouse model system to study the developmental and molecular events that lead to the etiology of HME in humans. We are particularly interested in the regulatory changes that occur in developing cartilage and bone that give rise to altered bone structure.
Abbreviated Curriculum Vitae
Education
B.A., 1976: Biology and Chemistry at California State University, Sacramento, CA
Ph.D., 1983: Cellular, Molecular and Developmental Biology at Indiana Universtiy, Bloomington, Indiana. Dissertation title "Analysis of Maternal Histone mRNA Translation, Transcription and Localization".
Research and Professional Activities
1983-85: Postdoctoral Fellowship, American Cancer Society, Stanford University, School of Medicine, Palo Alto, California
1985-86: Postdoctoral Fellowship, Veterans Administration,Stanford University, School of Medicine, Palo Alto, California
1986-92: Assistant Professor,Department of Biology, University of Houston, Houston, Texas
1987- : Permanent Member, Institute for Molecular Biology, University of Houston, Houston, Texas
1992-97: Associate Professor, Department of Biology, Unversity of Houston, Houston, Texas
1997 - : Professor, Department of Biology and Biochemistry, University of Houston, Houston, Texas
2000 - : Chairman, Department of Biology and Biochemistry, University of Houston, Houston, Texas
Professional Service and Awards
* HUGO editor for the Human Genome Database
* Scientific Advisor for the Langer Giedion Syndrome Association
* Member of the American Society for Human Genetics
Publications (Only EXT relevant publications listed)
H. Ludecke, C. Johnson, M.J. Wagner, D.E. Wells, C. Turleau, N. Tommerup, A. Latos- Bielenska, K-R. Sandig, P. Meinecke, B. Zabel and B. Horstemke. (1991) Molecular definition of the shortest region of overlap in the Langer-Giedion Syndrome. American Journal of Human Genetics 49:1197-1206.
A. Cook, W. Raskind, S. Blanton, R. Pauli, R. Gregg, C. Francomano, E. Conrad, G. Schmale, G. Schellenberg, E. Wijman, J. Hecht, D.E. Wells and M. Wagner, (1993) Genetic Heterogeneity in families with Hereditary Multiple Exostoses. American Journal of Human Genetics 53: 71-79.
M. Sapru, J.Gu, X. Gu, D. Smith, C-E.Yu, D.E. Wells and M.J. Wagner. (1994) A panel of radiation hybrids for human chromosome 8. Genomics 21: 208-216.
J.E. Parrish, Y. Wang, M.J. Wagner and D.E. Wells. (1994) Alignment of the physical and genetic maps of human 8q23-qter using a somatic cell hybrid mapping panel. Somatic Cell and Molecular Genetics 20:143-146.
H. Ludecke, M.J. Wagner, J. Nardman, B. LaPillo, P.J. Willems, E.A. Haan, M. Frydman, G.J.H. Hamers D.E. Wells and B. Horstemke. (1995) Molecular dissection of a contiguous gene syndrome: Localization of the genes involved on LGS. Human Molecular Genetics 4:31-36.
W.Wuyts, S Ramlakhan, W.V. Hul, J. T. Hecht, A.M.W. van der Ouweland, W.R. Raskin, F.C. Hofstede, E. Reyniers, D.E. Wells, B. deVries, E. U. Conrad, A. Hill, D. Zalatayev, J. Weissenbach, M.J. Wagner, E, Bakker, D.J.J. Halley and P.J. Willems. (1995) Refinement of the multiple exostoses locus (EXT2) to a 3 cM interval on chromosome 11. American Journal of Human Genetics 57: 382-387.
E. Shore, A. Cook, G. Hahn, F. Kaplan, J. Wozney, M.J. Wagner and D.E. Wells. (1995) BMP1 Sublocalizes on human chromosome 8: Molecular anatomy and orthopaedic implications. Clin. Ortho. Rel. Res. 311: 199-209.
J. Hou, J. Parrish, J. Siegel, M. Sapru, Y. Wang, A. Hill, H. Northrup, F.F.B. Elder, E. A. Haan, H. Ludecke, B. Horstemke, M.J. Wagner and D.E. Wells. (1995) A YAC contig spanning the LGS region on human chromosome 8: Sublocalization of EXTI and TRPSI. Genomics 29:87-97.
J. Ahn, H-J. Luedecke, S. Lindlow, W. Horton, B. Lee, M.J. Wagner. B. Horstemke, and D.E. Wells. (1995) Cloning the putative tumour suppressor gene for hereditary multiple exostoses (EXT1). Nature Genetics 11:137-143.
J.Z. Gu, M.J. Wagner, E.A. Haan and D.E. Wells. (1996) Detection of a megabase deletion in a patient with branchio-oto-renal syndrome (BOR) and tricho-rhino-phalangeal syndrome (TRPS); Implications for mapping and cloning the BOR gene. Genomics 31:201-209.
W. Chen, J. Hou, M.J. Wagner, and D.E. Wells. (1996) An integrated physical map covering 25 cM of human chromosome 8. Genomics 32:117-120.
S.H. Blanton, D. Hogue, M. Wagner, D.E. Wells, and J. Hecht. (1996) Hereditary multiple exostoses: Confirmation of linkage to chromosomes 8 and 11. American Journal of Medical Genetics 62:150-159
J. Hecht, D. Hogue, Y. Wang, S.H. Blanton, M. Wagner, L. Strong, W. Raskind, M. F. Hansen, and D.E. Wells. (1997) Hereditary multiple exostoses: Mutational studies of familial EXT1 cases and EXT associated malignancies American Journal of Human Genetics 60: 80-86
H-J. Luedecke, J. Ahn, X. Lin, A. Hill, M.J. Wagner, L. Schomburg, B.Horstemke, and D.E. Wells. (1997) Genomic organization and promoter structure of the human EXT1 gene. Genomics 40: 351-354.
D. E. Wells, A. Hill, X. Lin, J. Ahn, N. Brown, and M. J. Wagner. (1997) Identification of novel mutations in the human EXT1 tumor suppressor gene. Human Genetics 99: 612-615.
X. Lin and D.E. Wells. (1997) Isolation of the mouse cDNA homologous to the human EXT1 gene responsible for Hereditary Multiple Exostosis. DNA Sequence 7: 199-202.
C. Philippe, D.E. Porter, M.E. Emerton, D.E. Wells, A. Harnish, R W. Simpson and A.P. Monaco. Mutation Screeing of EXT1 and EXT2 genes in patients with hereditary multiple exostoses. American Journal of Human Genetics 61:520-528.
F. Ugolina, M. Chaffanet, R. Houlgatte, D. Patterson, D. E. Wells, C Auffray, D. Birnbaum and M-J. Pebusque. (1997) Regional assignment of 64 human gene transcripts on chromosome 8. Cytogenetics and Cell Genetics 77:197-200.
A. Hill, Y. Harada, E. Takahashi, M. J. Wagner and D. E. Wells (1997) FRA8E localizes close to the EXT1 gene and to 2 overlapping LGS deletion endpoints at 8q24.11, Cytogenetics and Cell Genetics 78:56-57.
W.R. Raskind, E. U. Conrad, M. Matsushita, E. M. Wijsman, D.E. Wells, L.J. Chapman, M.J. Wagner, J. Houck. (1998) Evaluation of locus heterogeneity and EXT1 mutations in 34 families with hereditary multiple exostoses. Human Mutation 11: 231-239.
X. Lin, L. Gan, W.H. Klein, and D.E. Wells, (1998) Expression and Functional Analysis of mouse EXT1, a homologue of the human multiple exostoses type 1 gene. Biochem. Biophys. Res. Comm. 248:738-743.
X. Lin, D.E. Wells and W. Kimberling , S. Kumar (1999) Human NDUFB9 gene: Genomic Organization and exclusion as a candidate gene associated with deafness disorder mapped to chromosome 8. Human Heredity 49:75-80..
X. Lin, G. Wei, Z. Shi, L. Dryer, J. Esko, D. E. Wells* and M. M. Matzuk, (2000) Disruption of Gastrulation and Heparan Sulfate Biosynthesis in EXT1 Deficient Mice.” Developmental Biology. 224:229-311. (*corresponding author)
President & Chief Executive Officer
Egea Biosciences
San Diego, California
858-509-3145
Email: genetics@egeabiosciences.com
Egea Biosciences is an innovative biotechnology company in San Diego, California, specializing in research and development in the area of genomics and genetic screening. Dr. Evans was formerly Eugene McDermott Distinguished Professor, Director of the McDermott Center for Human Growth and Development at the University of Texas Southwestern Medical Center in Dallas, Texas, and Director of the Human Genome Sequencing Center of the National Institutes of Health. From 1994 until 1999, Dr. Evans laboratory was one of six large scale DNA sequencing centers participating in the Human Genome Project, an international collaborative effort to determine the sequence of the entire human genome and discover all human genes. The Human Genome Project was completed in 2000 and the results will be published in early 2001. Prior to that, Dr. Evans was Professor and Director of the Molecular Genetics Laboratory at the Salk Institute for Biological Studies in San Diego California, from 1983 to 1994. Dr. Evans is co-founder of Nanogen, Inc., of San Diego, California, a biotechnology company developing microelectronic DNA chips for clinical and genetic testing. Dr. Evans is an expert in high throughput genomics, human genetics and biotechnology. He is an author of over 180 publications and hold six US and foreign patents. He is Editor in Chief of the professional journal Microbial and Comparative Genomics and Associate Editor of the journal Genomics. Dr. Evans research involves the discovery and analysis of genes responsible for inherited diseases and cancer, and the large scale analysis of genes on chromosome 11. Dr Evans lab discovered the gene EXT2 responsible for hereditary multiple exostosis type 2 and has published on the genetics and biochemistry of HME including a review article in Nature Genetics. Dr. Evans received his MD and PhD from the University of California, San Diego, in 1979, was a medical intern at Stanford University Medical Center and a Medical staff fellow at the National Institute of Child Health and Human Development in Washington DC. He first founded and then joined Egea Biosciences, Inc., in 1999.
Egea Biosciences, Inc., is a research and development company utilizing the vast information resources of the human genome project to develop innovative new diagnostic and therapeutic tools for medicine. Egea Biosciences, Inc., carries out contract research and development services for the pharmaceutical and biotechnology industry as well as limited genetic testing services. Egea utilizes state-of-the-art robotics and high speed DNA sequencing instruments as well as DNA chip genetic analysis provided by instrumentation from Nanogen Inc. As one of the discoverers of the EXT genes responsible for Hereditary Multiple Exostosis (HME), Dr, Evans laboratory has facilities and capabilities of prenatal and antenatal diagnostic testing, through sequencing or Chip analysis, of HME as well as other rare disorders. Though genetic diagnostic testing is not yet offered as a commercial service, it is anticipated that HME testing could be carried at Egea Biosciences, for research purposes only in early 2001. Patients or families interested in this service should contact Sarah Ziegler at dinosarah@prodidgy.net.
Howard Hughes Medical Institute
Department of Genetics
Harvard Medical School
200 Longwood Avenue
Boston, MA 021115
E-mail: perrimon@rascal.med.harvard.edu
Abbreviated Curriculum Vitae
Education
1981: Undergraduate at University of Paris VI "Maitrise of Biochemistry"
1983: Graduate Student at University of Paris VI "These de 3e cycle" Title: "Analyse clonale de l'ovogenese chez Drosophila melanogaster", Professor Madeleine Gans, thesis advisor
1983-1986: Postdoctoral Research Fellow at Case Western Reserve Universitiy in the laboratory of Dr. Anthony P. Mahowald
Appointments
1986-1993: Assistant Professor, Department of Genetics, Harvard Medical School
1986-1993: Assistant Investigator,Howard Hughes Medical Institute
1993-1996: Associate Professor, Department of Genetics,Harvard Medial School
1993-1997: Associate Investigator, Howard Hughes Medical Institute
1996 -present: Professor, Department of Genetics,Harvard Medical School
1997-present: Investigator, Howard Hughes Medical Institute
Awards
1985: Lucille P. Markey Scholor in Biomedical Sciences
1996: Honorary Master Degree, Harvard Medical School
Panels and Committees:
1991-1992: National Science Foundation, Division of Biological Instrumentation and Resources
1992: National Science Foundation, Academic Research Infrastructure
1994-1995: NCI.NIH, Member Special Study Section
1997: NINDS, NIH, AdHoc reviewer
1993-1998: National Science Foundation, Developmental Mechanisms
1995-2000: Drosophila Developmental Biology Meeting Committee, Crete
1996-present: U.S. Drosophila Stock Center Advisory Board
1999: Committee de direction. Marseille CNRS, France
Chief of Orthopaedic Surgery, The Children's Hospital of Philadelphia
Professor of Orthopaedic Surgery, University of Pennsylvania, School of Medicine
Office Address:
The Children's Hospital of Philadelphia
Orthopaedic Department
2nd Floor Wood Bldg.
34th & Civic Center Blvd.
Philadelphia, PA 19104-4399
Hereditary multiple exostosis (HME) is an autosomal dominant disorder manifested by the presence of multiple osteochondromas. Osteochondroma, the most common pediatric bone tumor, is a cartilage-capped exostosis, and HME represents a subset of patients with these lesions. Lesions are most frequently located in the juxta-epiphyseal region of rapidly-growing long bones, but are also commonly observed in the scapulae, ribs, and iliac crests. Osteochondromas are either sessile or pedunculated in morphology and can vary substantially in both size and number. The disorder is associated with characteristic progressive skeletal deformities. The prevalence of HME has been estimated to be 0.9 to two cases per 100,000. Linkage analysis has implicated mutations in the EXT gene family which encode glycosyltransferases that participate in the biosynthesis of heparin sulfate proteoglycans. Impaired expression of heparin sulfate has been associated with defective regulation of chondrocyte differentiation and organization. Patients with HME have an increased risk of sarcomatous transformation.
Education (including locations, dates and degrees obtained):
1975-1979 - BS, Indiana University
1979-1983 - MD, Indiana University
Hospital Training (including dates of internships, residencies, fellowships, etc.):
1983-1988 - Orthopaedic Surgery Residency, Grand Rapids/Michigan State University Orthopaedic Residency
1988-1989 - Clinical Pediatric Orthopaedic Fellowship, The Hospital for Sick Children, Toronto, Ontario, Canada
Current Professional Appointments:
Chairman, Division of Orthopaedic Surgery, The Children's Hospital of Philadelphia
Professor of Orthopaedic Surgery, University of Pennsylvania
Co-Director of the Pediatric Orthopaedic Surgery Fellowship, The Children's Hospital of Philadelphia
Certification and Recertification (including date(s):
1991 - American Board of Orthopaedic Surgeons
1993 - National Board of Medical Examiners
Licensure(s): Pennsylvania
Current Professional Activities/Committees:
1999-2001 President Medical Staff and Board of Trustees (Medical Staff Representative), The Children's Hospital of Philadelphia
2001-2002 President, Surgical Associates Research and Education Foundation, The Children’s Hospital
1998 Program for Chiefs of Clinical Services, Harvard School of Public Health,
2000 Advanced Program for Chiefs of Clinical Services, Harvard School of Public Health
2002-03 Mentor, AAOS Leadership Fellow Program
2001- Board of Directors, Children’s Surgical Associates, The Children’s Hospital of Philadelphia.
2000- Leadership Council, Wharton School, University of Pennsylvania (15 month program).
2000- Children’s Health Network Board of Directors
2000- Promotions Committee, Department of Orthopaedic Surgery, University of Pennsylvania
1998- Children’s Physician Organization Board of Directors
1998- Executive Committee, Department of Orthopaedic Surgery, University of Pennsylvania
Role in Residency and Fellowship Training Program:
Supervision and instruction of Orthopaedic Surgery residents during rotation at CHOP. Attending rounds and supervision of inpatient care. Supervision and Instruction of 1 Orthopaedic Surgery Clinical Fellow per year; director and supervision of research fellow. Formal core curriculum lectures in pediatric orthopaedic surgery for orthopaedic surgery residents et al, every morning, five days per week, one-hour lectures.
Important publications during the last five years:
Dormans JP and Pill S: Fractures through bone cysts: Unicameral bone cysts, aneurismal bone cysts, fibrous cortical defects, and non ossifying fibromas. Instructional Course Lecture, Volume 51, Section 10 (Tumors), Chapter 48, Pages 457- 468, The American Academy of Orthopaedic Surgeons, 2002.
Pierz K and Dormans JP: Multiple Hereditary Osteochondromatosis. In "Genetics and Childhood Disorders" symposium in Clinical Orthopaedics and Related Research, Volume 401, pages 49-59, August 2002.
Dormans JP: Evaluation and Management of Children with Suspected Cervical Spine Trauma. The Journal of Bone and Joint Surgery, Volume 84A, Number 1, Pages 123-132, January 2002.
Stieber JR, Pierz KA and Dormans JP: "Multiple Hereditary Exostoses: A current understanding of clinical and genetic advances." The University of Pennsylvania Orthopaedic Journal. Volume 14, pages 39-48, 2001.
Dormans JP, Fisher R and Pill S: Orthopaedics in The Developing World: Present and future concerns. The Journal of The American Academy of Orthopaedic Surgeons, Volume 9, Number 5, 289-296, September/October 2001.
- IRCCS “Casa Sollievo della Sofferenza”
Opera di Padre Pio da Pietrelcina
Laboratorio di Ricerca Unità di Terapia Genica e Oncologia
Poliambulatorio “Giovanni Paolo II”
Viale dei Cappuccini,
71013 San Giovanni Rotondo (FG) (ITALY)
- University Campus Bio-Medico
Laboratory for Molecular Medicine and Biotechnology
Via E Longoni, 83
00155 Rome (ITALY)
Principal investigator: Prof. VM Fazio M.D. (Fazio@unicampus.it),
D Seripa Ph.D. (dseripa@operapadrepio.it)
MG Matera Ph.D. (mgmatera@operapadrepio.it)
Clinical Groups:
- Rome
Principal Investigator: Dr. G. Falcone (falconegian@libero.it)
Tel.: + 39 338 5608078
- Università degli Studi di Messina
Istituto di Clinica Ortopedica
Policlinico G. Martino
Via Consolare Valeria
98125 Messina, Italy
Principal Investigator: Prof. MA Rosa (e-mail: rosa.ma@tiscalinet.it)
Tel.: + 39 338 6629847
Scientific Updating
Hereditary Multiple Exostoses (HME) is the most common type of benign tumor with a low but significant risk of malignant trasformation. It is an autosomal dominant inherited disorder with a complex pathogenesis and genetic heterogeneity. At least two loci are known to be associated with HME, EXT1 and EXT2 genes. The mutations in these genes cause the abrogation of the protein involved in the Heparan Sulfate synthesis.
Actually, we have analysed 60 families with hereditary multiple exostoses, all italian descents, and characterized 32 families with mutation in EXT genes (70% in EXT1 gene and 30% in EXT2 gene) (>90 affected subjects). Fourteen new mutations in EXT1 and six in EXT2 genes have been identified in Italian population. Most mutations cause premature truncation of corresponding protein (exostosen), the other are missense mutations in specific functional domains of the protein.
Technology:
• Single-strand conformational polymorfism (SSCP) or DHPLC (Transgenomics Wave) for rapid molecular screening;
• direct sequencing (MegaBace 500, Amersham);
• immunohistochemistry on tissues
• cell cultures.
Studies and Interest on:
• EXT mutation screening
• genotype-phenotype correlations
• immunohistochemical studies on molecular mechanism of exostoses development
• molecular mechanism of malignant transformation in HME-related and –non related bone tumors
PUBLICATIONS:
M Gigante, MG Matera, D Seripa, AM Izzo, R Venanzi, A Giannotti, MC Digilio, C Gravina, M Lazzari, G Monteleone, M Monteleone, B Dallapiccola, VM Fazio. Ext-mutation analysis in Italian sporadic and hereditary osteochondromas. Int J Cancer 2001;95:378-383.
Manuscript in preparation, November 2003
Short comunications:
MG Matera, D Seripa, C Gravina, M Rinaldi, G Falcone, RP D’Andrea, V De Santis, L Proietti, VM Fazio. Mutation screening of the EXT1 and EXT2 genes in italian families with multiple hereditary osteocondromas. J Tumor Marker Oncol 2003; 18: 225
CONGRESS AND MEETINGS:
MG Matera, D Seripa, C Gravina, M Gigante, R Venanzi, A Giannotti, MC Digilio, G Monteleone, M Monteleone, B Dallapiccola, VM Fazio. Analisi dei geni EXT-1 e 2 in famiglie italiane con osteocondromatosi multipla eredofamiliare. 4° Congresso Nazionale della Società Italiana di Genetica Umana, Orvieto 28-30 Novembre 2001. Proceedings p. 45.
MG Matera, D Seripa, C Gravina, B Dallapiccola, VM Fazio. Osteocondromatosi multipla familiare: spettro delle mutazioni nella popolazione italiana. V Congresso della Società Italiana di Genetica Umana. Verona, 25-27 settembre 2002.
D Seripa, MG Matera, C Gravina, RP D’Andrea, M Rinaldi, G Falcone, V De Santis, L Proietti, VM Fazio. Hereditary multiple exostoses: a proliferative disorder of bone. VI Congresso Nazionale della Società Italiana di Genetica Umana. Verona 24-27 settembre 2003. Riassunti di comunicazioni e poster p. 483.
MG Matera, D Seripa, C Gravina, M Rinaldi, G Falcone, RP D’Andrea, V De Santis, L Proietti, VM Fazio. Ruolo dei geni oncosoppressori EXT1 ed EXT2 nella patogenesi della condromatosi multipla ereditaria. Oncologie Muscolo Squeletique. Congresso Italo-Francese. Firenze 8-11 ottobre 2003