Stadtman Tenure Track Investigator
NIH/NIDCR
Building 30 Room 326
30 Convent Dr. MSC 4340
Bethesda, MD 20892-4340
United States
Mammalian development relies on the precise execution of highly coordinated cell-fate decisions by stem cells, which can undergo self-renewal, reversibly exit into a quiescent state, or terminally commit to a cell differentiation program. To orchestrate these decisions, stem cells make frequent use of ubiquitylation, an essential post-translational modification that alters the stability, activity, localization, or interaction landscape of target proteins. The Werner lab combines proteomic and biochemical approaches with human embryonic stem cell culture to determine the molecular mechanism of how ubiquitylation controls these cell-fate choices—in particular, those involved in neural crest specification and whose mis-regulation leads to the craniofacial development disease Treacher Collins Syndrome. Results from these studies will provide molecular insights into important aspects of human development and into the origin of developmental diseases, which will be useful for developing novel therapeutic approaches.
Dr. Achim Werner received his Ph.D. from the International Max Planck Research School for Molecular Biology in Göttingen, Germany. As a California Institute of Regenerative Medicine fellow, Dr. Werner then performed his postdoctoral work at the University of California, Berkeley, where he studied the role for ubiquitylation enzymes in human embryonic stem cell maintenance and differentiation. By combining mass spectrometry-based approaches with stem cell differentiation assays, biochemical techniques, and ribosome profiling, Dr. Werner’s work has elucidated a novel pathway that regulates the function of newly synthesized ribosomes to allow stem cells to adopt a neural crest cell fate during differentiation. On the basis of these findings, Dr. Werner was awarded an NIH/NIDCR K99 Pathway to Independence Award in 2015. In 2017, Dr. Werner launched his independent research program at the NIDCR as Chief of the Stem Cell Biochemistry Unit.
- Poulter JA, Collins JC, Cargo C, de Tute RM, Evans P, Ospina Cardona D, Bowen DT, Cunnington JR, Baguley E, Quinn M, Green M, McGonagle D, Beck DB, Werner A, Savic S (2021) Novel somatic mutations in UBA1 cause VEXAS syndrome. Blood 2021 Mar 9;blood.2020010286.
- Beck DB, Basar MA, Asmar AJ, Thompson J, Oda H, Uehara DT, Saida K, Pajusalu S, Tavlik I, D’Souza P, Bodurtha J, Mu W, Barañano KW, Miyake N, Wang R, Kempers M, Nishimura Y, Okada S, Kosho T, Dale R, Mitra A, Macnamara E, Undiagnosed Diseases Network, Matsumoto N, Inazawa J, Walkiewicz M, Õunap K, Tifft CJ, Aksentijevich I, Kastner DL, Rocha PP, Werner A (2021) Linkage-specific deubiquitylation by OTUD5 defines an embryonic pathway intolerant to genomic variation. Sci Adv, 2021 Jan 21. doi: 10.1126/sciadv.abe2116.
- Beck DB, Ferrada MA, Sikora KA, Ombrello AK, Collins J, Pei W, Ospina Cardona D, Balanda N, Wu Z, Patel B, Manthiram K, Ross D, Groarke EM, Gutierrez-Rodrigues F, Hoffmann P, Rosenzweig S, Nakabo S, Dillon LW, Hourigan CS, Tsai WL, Gupta S, Carmona-Rivera C, Asmar, AJ, Xu L, Oda H, Goodspeed W, Barron KS, Nehrebecky M, Jones A, Laird RS, Deuitch N, Dorota Rowczenio D, Rominger E,Wells KV, Lee CCR,Wang W, Trick M, NISC Comparative Sequencing Program, Wigerblad G, Brooks S, Dell’Orso S, Deng Z,Chae JJ, Dulau-Florea A, Malicdan MCV, Novacic D, Colbert RA, Kaplan MJ, Gadina M, Savic S, Lachmann HJ, Abu-Asab M, Solomon BD, Retterer K, Gahl WA, Burgess SM, Aksentijevich I, Young NS, Calvo KR, Werner A, Kastner DL, Grayson PC (2020) Somatic Mutations in UBA1 and Severe Adult-Onset Autoinflammatory Disease. N Eng JMed 2020 Oct 27. doi: 10.1056/NEJMoa2026834.
- Werner A, Iwasaki S, McGourty CA, Medina-Ruiz S, Teerikorpi N, Fedrigo I, Ingolia NT, Rape M. Cell-fate determination by ubiquitin-dependent regulation of translation. Nature. 2015 Sep 24;525(7570):523-7. doi: 10.1038/nature14978. PMID: 26399832.
- Werner A, Disanza A, Reifenberger N, Habeck G, Becker J, Calabrese M, Urlaub H, Lorenz H, Schulman B, Scita G, Melchior F. SCFFbxw5 mediates transient degradation of actin remodeller Eps8 to allow proper mitotic progression. Nat Cell Biol. 2013 Feb;15(2):179-88. doi: 10.1038/ncb2661. Epub 2013 Jan 13. PMID: 23314863.