Philip J. Mason, Ph.D.

Phil Mason
  • Professor
    • Department of Medicine
      • Hematology Division
    • Department of Genetics
  • Research interests
    • Inherited aplastic anemias
    • Dyskeratosis congenita
    • Telomerase

Research

My research is directed to understanding the roles of ribosome biogenesis and telomere maintenance in human disease. We are particularly interested in the genetics and pathogenesis of two inherited bone marrow failure syndromes, namely dyskeratosis congenita and Diamond Blackfan Anemia.

Dyskeratosis congenita has X-linked, autosomal dominant and recessive forms. We have identified a gene DKC1, which encodes a protein called dyskerin, that is responsible for the X-linked form of the disease. Dyskerin is a nucleolar protein that is part of snoRNAs that are important in ribosomal RNA processing. Dyskerin is also part of the telomerase complex that maintains the integrity of the telomeres that cap the chomosome ends. We use cell and molecular biological approaches to study the mechanisms by which dyskerin modifies newly synthesized ribosomal RNA and stabilizes the telomerase complex. By studying the consequences of dyskerin mutations in cell and animal models we hope to understand the pathogenesis of DC and the roles of ribosome biogenesis and telomere maintenance in normal physiology. We have recently found that a dyskerin mutation that causes DC in humans causes a growth defect in mice which is telomerase dependent but independent of telomere length. The mutation also leads to an increase in the number of DNA damage foci at telomeres. This suggests a novel role for dyskerin in telomere maintenance.

Diamond Blackfan Anemia is a pure red cell aplasia which presents usually in childhood, sometimes with a variety of associated developmental abnormalities. Recently mutations in several ribosomal proteins from either subunit have been found to cause DBA. We wish to understand how mutations in ribosomal proteins give rise to failure of erythropoiesis. We use cell and animal models to study the role of ribosomal proteins in ribosome biogenesis and function. We have recently studied the effect of depleting cells of specific ribosomal proteins. We find that in all cases production of the ribosome subunit where the protein resides is inhibited with the degradation of other proteins from the same subunit. We conclude DBA, in which individual ribosomal proteins are haploinsufficient, results from a failure of ribosome biogenesis. We are now using erythroid cell lines to study why inefficient ribosome biogenesis should specifically effect red cell development.

Telomerase

The relationship between H/ACA snoRNPs and telomerase RNPs

Telomerase RNA has a H/ACA box sequence at its 3' end and is associated with the same 4 proteins that are present in the snoRNP. Other proteins are present in the telomerase complex including the telomerase reverse transcriptase TERT.

From: Mason PJ, Wilson DB, Bessler M
Dyskeratosis congenita -- a disease of dysfunctional telomere maintenance.
Curr Mol Med 2005 Mar;5(2):159-70

Biographical Sketch

Education

1976 BSc (Hons) Class 1 in Biological Sciences, specialising in Genetics, University of Edinburgh, Scotland
1976-1979 Postgraduate research, laboratory of Dr. John Bishop, Department of Genetics, University of Edinburgh, Scotland
1980 PhD awarded, "The cloning of polyadenylated ribonucleic acid sequences from Drosophila"

Academic Positions & Employment

1971-1972 Junior technician, MRC Human Biochemical Genetics Unit, University College, London
1979-1980 Post doctoral research fellow, Dr. John Bishop's laboratory, Department of Genetics, University of Edinburgh, Scotland
1980-1982 European Molecular Biology Organisation long-term fellow, laboratory of Prof. Alfred Tissieres, Department of Molecular Biology, University of Geneva, Switzerland
1982-1985 Research fellow, Developmental Gene Expression Laboratory (Department head: Dr. Jeffrey Williams), Imperial Cancer Research Fund, Mill Hill Laboratories, London
1985-1992 Lecturer, Department of Haematology. Royal Postgraduate Medical School, Hammersmith Hospital, London
1992-2000 Senior Lecturer, Department of Haematology. Royal Postgraduate Medical School, Hammersmith Hospital, London
2000-2003 Reader in Molecular Genetics. Department of Haematology. Imperial College School of Medicine, Hammersmith Hospital, London
2004-2007 Associate Professor (Research Track), Department of Medicine, Division of Hematology, Washington University, St. Louis, MO
2007-present Research Professor, Department of Medicine, Division of Hematology, Washington University, St. Louis, MO
2007-present Professor, Department of Genetics, Washington University, St. Louis, MO

Awards & Invited Lectures

1980 EMBO long term fellowship
1987 Organiser, Royal Postgraduate School Short Course "Techniques in Human Molecular Genetics," Royal Postgraduate School, London
1989 Organiser, EMBO Practical Course "Modern Techniques in Human Genetics," Royal Postgraduate School, London
1995 Invited lecturer, Seminario Internacional de Farmaceuticos, Sao Paulo. Brazil
2003 Edward J. Mallinckrodt, Jr. Foundation Award
2004 Invited lecturer, British Association for Cancer Research, Conference on Stem Cells and Telomerase: Targets for Transformation & Therapeutic Applications, Cyprus
2005 Invited lecturer, The Ribo-Club, Sherbrooke, Quebec, Canada
2006 Invited lecturer, Beijing Union Medical College, Beijing, China
2006 Invited lecturer, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science, Tianjin, China
2006 Invited lecturer, Instituto de Investigaciones Biomedicas CSIC/UAM, Madrid, Spain
2009 Invited speaker, European Haematology Association annual meeting, Berlin, Germany
2009 Invited lecturer, Biomedical Research Center on Rare Diseases Workshop, Madrid, Spain

Academic Societies

  British Society of Haematology
  Genetics Society
  Biochemical Society
  British Society of Parasitology
  American Society of Hematology
  RNA Society