Our lab is interested in the biology and genetics of age-related disease. Specifically, we are interested in syndromes of telomere shortening which capture both the degenerative and cancer-prone phenotypes of aging. Human syndromes associated with telomere shortening were first identified in the context of dyskeratosis congenita, a premature aging syndrome that predisposes to cancer. Dyskeratosis congenita patients prematurely die from aplastic anemia, the prototype of stem cell failure disorders. Mutations in the essential components of telomerase also cause progressive and fatal scarring of the lungs in idiopathic pulmonary fibrosis. At least 10% of individuals with idiopathic pulmonary fibrosis carry mutant telomerase genes or have short telomeres. The goal of research in our lab is to understand the genetics and pathophysiology of telomere-mediated disorders in hopes of delineating translational approaches to their treatment.
Clinical Trial Keywords:
Dyskeratosis Congenita, Idiopathic Pulmonary Fibrosis Genetics, Bone Marrow Failure, Constitutional Aplastic Anemia, Familial Myelodysplastic Syndrome, Hoyeraal Hreidarsson Syndrome, Telomere, Telomerase, Telomeres, Telomerase, Bone Marrow Failure, Genetics, Dyskeratosis Congenita
1.Armanios M, Grossman SA, Yang S, White B, Orens J. Transmission of glioblastoma multiforme after bilateral lung transplantation, Neuro-oncology 2004,6259-63.
2. Armanios M, Xu R, Forastiere A, Haller D, Kugler J, Benson AB. Adjuvant Chemotherapy for Resected Adenocarcinoma of the Esophagus, Gastro-esophageal (GE) Junction and Cardia (E8296): A Phase II Trial of the Eastern Cooperative Oncology Group, Journal of Clinical Oncology 2004:22,4495-9.
3. Armanios M, Chen JL, Chang Y-P, Brodsky RA, Hawkins A, Griffin CA, Eshleman JR, Cohen AR, Chakravarti A, Hamosh A, Greider CW. Haploinsufficiency of Telomerase Reverse Transcriptase Leads to Anticipation in Autosomal Dominant Dyskeratosis Congenita, Proceedings of the National Academy of Sciences 2005:102(44),15960-4.
4. Hao L-Y, Armanios M, Strong MA, Karim B, Feldser DM, Huso D, Greider CW. Short Telomeres, Even in the Presence of Telomerase, Limit Tissue Renewal Capacity, Cell 2005:123,1121-31.
5. Armanios MY, Chen JL, Cogan JD, Alder JK, Ingersoll RG, Markin C, Lawson WE, Xie M, Vulto I, Phillips JA, Lansdorp PM, Greider CW, Loyd JE. Telomerase Mutations in Families with Idiopathic Pulmonary Fibrosis, New England Journal of Medicine 2007:316,1317-26.
6. Alder JK, Chen JL, Lancaster L, Danoff S, Su SC, Cogan JD, Vulto I, Xie M, Qi X,Tuder, RM, Phillips JA 3rd, Lansdorp PM, Loyd JE, Armanios MY. Short telomeres are a risk factor for idiopathic pulmonary fibrosis, PNAS 2008:105(35),13051-6.
7. Armanios M, Alder JK, Parry EM, Karim B, Strong MA, Greider CW. Short telomeres are sufficient to cause the degenerative defects associated with aging,American Journal of Human Genetics 2009:85(6):823-32.
8. Parry EM, Alder JK, Lee S, Phillips JA3rd, Loyd JE, Duggal P, Armanios M. Decreased dyskerin levels as a mechanism of telomere shortening in X-linked dyskeratosis congenita, Journal of Medical Genetics 2011:48(5),327-33. epub Mar 17 2011
9. Alder JK, Cogan JD, Brown AF, Anderson CJ, Lawson WE, Lansdorp PM, Phillips JA 3rd, Loyd JE, Chen J J-L, Armanios M. Ancestral mutation in telomerase manifests as familial pulmonary fibrosis and leads to defects in repeat addition processivity,PLoS Genetics 2011:7(3), e1001352. epub Mar 31 2011
10. Guo N, Parry EM, Li L, Kemboui F, Lauder N, Hussain M, Berggren P-O, Armanios M. Short telomeres compromise β-cell signaling and survival, PLoS One 2011:6(3), e17858. epub Mar 10 2011
11. Parry EM, Alder JK, Qi X, Chen J J-L, Armanios M. Syndrome complex of bone marrow failure and pulmonary fibrosis predicts a germline defect in telomerase, Blood 2011:117(21),5607-11. epub Mar 24 2011
12. Alder JK, Guo N, Kembou F, Parry EM, Anderson CJ, Gorgy AI, Sussan T, Biswal S,Mitzner W, Tuder RM, Armanios M. Telomere length is a determinant of emphysema susceptibility, American Journal of Respiratory and Critical Care Medicine, epub July 14 2011
1.Armanios M and Greider CW. Telomerase and Cancer Stem Cells. Cold Spring Harbor Symposia on Quantitative Biology: Molecular Approaches to Controlling Cancer 2005:70,205-08.
2.Armanios MY. Syndromes of Telomere Shortening. Annual Review of Human Genetics and Genomics 2009:10,45-61. epub April 29
3.Savage SA, Dokal I, Armanios M, Aubert G, Cowen E, Domingo D, Giri N, Greene N, Orchard P, Tsilou E, Van Waes C, Wong J, Young NS, Alter BP. Meeting Report: The First NIH Clinical Research Workshop Pediatric Blood and Cancer,53(3):520-3.* 12 citations
4.Armanios M. Telomerase and Idiopathic Pulmonary Fibrosis. Mutation Research, In press.