Jonathan K. Alder, PhD
Assistant Professor of Medicine

Dr. Alder is a faculty member in the Department of Medicine, University of Pittsburgh School of Medicine

Office Location:
BST W1246
200 Lothrop St.
Pittsburgh, PA 15261
Contact Information:
Office Telephone: (412) 624-8681

Research Interests

Our laboratory in focused on understanding how telomeres contribute to human health and disease. Telomeres are DNA/protein caps at the ends of chromosomes that are essential to genome stability. Due to the "end replication problem", telomeres shorten each time a cell divides and when they become too short, they trigger apoptosis or permanent cell cycle arrest. Telomeres are maintained by telomerase, composed of a reverse transcriptase (TERT) that synthesizes new telomeres from an endogenously encoded RNA template (TR). Telomerase expression is tightly controlled such that only a few cell types have telomerase activity. When telomeres become too short, they cause a spectrum of diseases including bone marrow failure, liver fibrosis, and, most commonly, lung fibrosis. Our lab is primarily focused on understanding how telomere dysfunction causes lung disease. We approach this question using cell biology, animal modelling, and clinical samples that are available here at Pitt.

In addition, All cancers must overcome the end replication problem to maintain tumor growth and telomerase inhibitor are currently undergoing clinical trial. My laboratory is interested in understanding the mechanisms by which cancer cells escape the tumor suppressive effects of telomeres. Recent research has shown that mutations in the promoter of TERT are some of the most common mutations found in all of cancer. However, not all cancers maintain their telomeres by reactivating telomerase and diverse mechanism exist by which cancers overcome the end replication problem. My laboratory is interested in exploring all the mechanism by which telomeres are maintained in cancer cells in the hopes of identifying potential targets for limiting cancer growth.

Selected Publications

  1. Iasella CJ, Winters SA, Kois A, Cho J, Hannan SJ, Koshy R, Moore CA, Ensor CR, Lendermon EA, Morrell MR, Pilewski JM, Sanchez PG, Kass DJ, Alder JK, Nouraie SM, McDyer JF. Idiopathic pulmonary fibrosis lung transplant recipients are at increased risk for EBV-associated posttransplant lymphoproliferative disorder and worse survival. Am J Transplant. 2020 May;20(5):1439-1446. doi: 10.1111/ajt.15756. Epub 2020 Jan 22. PubMed PMID: 31874120.
  2. Jiang M, Roth MG, Chun-On P, Sullivan DI, Alder JK. Phenotypic Diversity Caused by Differential Expression of SFTPC-Cre Transgenic Alleles. Am J Respir Cell Mol Biol. 2020 Mar 24;. doi: 10.1165/rcmb.2019-0416MA. [Epub ahead of print] PubMed PMID: 32208105.
  3. Zhang Y, Jiang M, Nouraie M, Roth MG, Tabib T, Winters S, Chen X, Sembrat J, Chu Y, Cardenes N, Tuder RM, Herzog EL, Ryu C, Rojas M, Lafyatis R, Gibson KF, McDyer JF, Kass DJ, Alder JK. GDF15 is an epithelial-derived biomarker of idiopathic pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol. 2019 Oct 1;317(4):L510-L521. doi: 10.1152/ajplung.00062.2019. Epub 2019 Aug 21. PubMed PMID: 31432710; PubMed Central PMCID: PMC6842909.
  4. Ringer, K.P., Roth, M.G., Garey, M.S., Piorczynski T.B., Suli, A., Hansen, J.M., Alder, J.K. Comparative Analysis ls Lipid-Mediated CRISPR-Cas9 Genome Editing Techniques. Cell Biol Int. 2018. 42(7):849-858. PMCID: PMC5999541
  5. Alder, J.K. Hanumanthu, V.S., Strong, M.A., DeZern, A.E., Stanley, S.E., Takemoto, C.M., Danilova, L., Applegate, C.D., Bolton, S.G., Mohr, D.W., Brodsky, R.A., Casella, J.F., Greider, C.W., Jacson, J.B., Armanios, M. Diagnositic utility of telomere length testing in a hospital-based setting. PNAS, 2018. 115(10):E2358-E2365. PMCID: PMC5877993
  6. Stanley S.E., Gable D.L., Wagner C.L., Carlile T.M., Hanumanthu V.S., Podlevsky J.D., Khalil S.E., DeZern A.E., Rojas-Duran M.F., Applegate C.D., Alder J.K., Parry E.M., Gilbert W.V., Armanios M. Loss-of-function mutations in the RNA biogenesis factor NAF1 predispose to pulmonary fibrosis-emphysema. Science Translational Medicine, 2016. 8(351):351ra107. PMID:27510903
  7. Sessions, J.W., Skousen, C.S., Price, K.D., Hanks, B.W., Hope, S., Alder, J.K., Jensen, B.D. CRISPR-Cas9 directed knock-out of a constitutively expressed gene using lance array nanoinjection. Springerplus, 2016. 5(1):1521. PMCID: PMC5017990
  8. Alder, J.K., Barkauskas, C.E., Limjunyawong, N., Stanley, S.E., Kembou, F., Tuder, R.M., Hogan, B.L., Mitzner, W., Armanios, M. Telomere dysfunction causes alveolar stem cell failure. PNAS, 2015. 112(16):5099-104. PMCID: PMC4413294
  9. Alder, J.K., Stanley, S.E., Wagner, C.L., Hamilton, M., Hanumanthu, V.S., Armanios, M., Exome sequencing identifies TINF2 in a family with pulmonary fibrosis. Chest, 2015. 147(5):1361-1368. PMID: 25539146
  10. Stanley, S.E., Chen, J.J., Alder, J.K., Hansel, N.N., Mathias, R.A., Qi, X., Rafaels, N.M., Wise, R.A., Silverman, E.K., Barnes, K.C., Armanios, M. Telomerase mutations in smokers with severe emphysema. JCI, 2015. 125(2):563-70. PMCID: PMC4319417
  11. Alder, J. K., Parry, E.M., Yegnasubramanian, S., Wagner, C.L., Lieblich, L.M., Auerbach, R., Auerbach, .AD., Wheelan, S.J., Armanios, M. Telomere phenotypes in females with heterozygous mutations in the dyskeratosis congenita 1 (DKC1) gene. Hum Mutat, 2013. 34(11):1481-5. PMCID: PMC3926107
  12. Alder, J. K., Guo, N., Kembou, F., Perry, E.M., Anderson, C.J., Gorgy, A.I., Walsh, M.F., Tuder, R.M., Armanios, M. Telomere length is a determinant of Emphysema Susceptibility. Am J Respir Crit Care Med. 2011. 184: 904-912.
  13. Parry, E. M., Alder, J. K., Lee, S. S., Phillips, J. A., 3rd, Loyd, J. E., Duggal, P. and Armanios, M., Decreased dyskerin levels as a mechanism of telomere shortening in X-linked dyskeratosis congenita. J Med Genet, 2011. 48(5): p. 327-33. PMCID: PMC3088476
  14. Parry, E. M., Alder, J. K., Qi, X., Chen, J. J. and Armanios, M., Syndrome complex of bone marrow failure and pulmonary fibrosis predicts germline defects in telomerase. Blood, 2011. 117(21): p. 5607-11. PMCID: PMC3110022
  15. Alder, J. K., Cogan, J. D., Brown, A. F., Anderson, C. J., Lawson, W. E., Lansdorp, P. M., Phillips, J. A., 3rd, Loyd, J. E., Chen, J. J. and Armanios, M., Ancestral mutation in telomerase causes defects in repeat addition processivity and manifests as familial pulmonary fibrosis. PLoS Genet, 2011. 7(3): p. e1001352. PMCID: PMC3069110