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BIOGRAPHICAL NOTES ABSTRACT Holoprosencephaly (HPE) is the most common structural anomaly of the Academic Studies: B. Sc. University of British Columbia, 1992 M. Sc. University of Toronto, 1999 human brain, resulting from incomplete cleavage of the developing forebrain during embryogenesis. Haploinsufficient mutations in TG-Interacting Factor (TGIF) were GRADUATE STUDIES previously identified in a subset of HPE families and sporadic patients, and this gene is located within a region of Chromosome 18 that is associated with non-random chromosomal aberrations in HPE patients. TGIF is a transcription factor that contains a three amino acid loop extension (TALE) homeodomain and functions both as a co-repressor of the TGF- pathway and as a competitor of the retinoic Field of Study: Courses MEDG520 MEDG530 MEDG540 Medical Genetics Advanced Human Molecular Genetics Molecular & Cellular Biology of Cancer Seminar Instructors Dr. Brown & Dr. Simpson Dr. Takei Dr. Dill & Dr. Brown acid pathway. Mice made deficient for Tgif exhibited laterality defects and growth retardation, and developed kinked tails. Analysis of Tgif -/- mouse embryonic fibroblasts (MEFs) in vitro demonstrated that Tgif regulates proliferation and progression through the G1 cell cycle phase. Wild-type human TGIF was able to rescue this proliferative defect in MEFs. In contrast, a subset of human Tgif mutations detected in HPE patients was unable to rescue the proliferative defect. AWARDS NIH Travel Scholarship, Holoprosencephaly Conference, 2004 Keystone Symposia Travel Scholarship, 2004 Albert B. and Mary Steiner Travel Award, UBC, 2004 Department of Medical Genetics Retreat Poster Award, UBC, 2003 Effie I Lefeaux Scholarship in Mental Retardation, 2001 However, an absence of Tgif did not alter the normal inhibition of proliferation caused by treatment with TGF- or retinoic acid. Developmental control of proliferation by Tgif may play a role in the pathogenesis of HPE. PUBLICATIONS Mar, L and Hoodless, PA. Embryonic fibroblasts from mice lacking Tgif were defective in cell cycling. Mol Cell Biol. 26(11):4302-4310. PRESENTATIONS Mar, L. and Hoodless, PA. Characterization of the Tgif knockout mouse. Third NIH Conference on Holoprosencephaly (HPE): Midline and Laterality Development. April 18-20, 2004, National Institutes of Health, Bethesda, Md., USA. Mar, L. and Hoodless, PA. Functional analysis of the Tgif knockout mouse. Northwest Developmental Biology Conference. March 18-20, 2004. Friday Harbor Laboratories, Wa., USA. SUPERVISORY COMMITTEE Dr. Pamela A. Hoodless, Research Supervisor (Medical Genetics) Dr. Connie Eaves (Medical Genetics) Dr. Rob Kay (Medical Genetics) Dr. Muriel Harris (Medical Genetics) T HE UNIVERS IT Y OF BRIT ISH COLUMBIA PROGRAMME The Final Oral Examination For the Degree of DOCTOR OF PHILOSOPHY (Medical Genetics) LYNN MAR M.Sc. University of Toronto, 1999 Tuesday, July 25, 2006, 4 pm Room 200, Graduate Student Centre “Role of TGIF in Cell Cycle Control and Establishment of Laterality” EXAMINING COMMITTEE Chair: Dr. Wolfram Tetzlaff (Zoology) Supervisory Committee: Dr. Pamela A. Hoodless, Research Supervisor (Medical Genetics) Dr. Connie Eaves (Medical Genetics) University Examiners: Dr. Wan L. Lam (Pathology & Laboratory Medicine) Dr. Jan M. Friedman (Medical Genetics) External Examiner: Dr. James C. Cross The University of Calgary Calgary, AB