Helen Blau

Helen Margaret Blau is an American biologist and the Donald E. and Delia B. Baxter Foundation Professor and Director of the Baxter Laboratory for Stem Cell Biology at Stanford University School of Medicine. She is known for establishing the reversibility of the mammalian differentiated state. Her landmark papers showed that nuclear reprogramming and the activation of novel programs of gene expression were possible, overturning the prevailing view that the differentiated state was fixed and irreversible.[1][2][3][4] Her discoveries opened the door for cellular reprogramming and its application to stem cell biology.[5][6]

Helen M. Blau
Helen Blau, 2013
Born
London, England
CitizenshipBritish, United States
Alma materUniversity of York
Harvard University
SpouseDavid Spiegel
ChildrenDaniel Blau Spiegel, Julia Blau Spiegel
Scientific career
FieldsDevelopmental biology, Regenerative medicine, Stem cell biology
InstitutionsStanford University Medical School
WebsiteBlau Lab website

Biography

Helen Blau was born in London and is a dual citizen of the United States and Great Britain. She earned a B.A. from the University of York in England and an M.A. and Ph.D. in biology from Harvard University with Fotis C. Kafatos. After a postdoctoral fellowship with Charles J. Epstein in the Departments of Biochemistry and Biophysics and the Division of Medical Genetics at UCSF, she joined the faculty at Stanford University in 1978. She was awarded an endowed chair in 1999 and named Director of the Baxter Laboratory for Stem Cell Biology in 2002.[7][8][9]

Blau is known for her support of women in science and success in mentoring numerous young scientists who comprise the next generation of academic leaders in muscle biology and regenerative medicine.[8]

Research

In the 1980s Dr. Blau's findings challenged the prevalent view that the mammalian differentiated state is fixed and irreversible.[4] In her famous heterokaryon experiments she fused differentiated cells of two different species to form stable non-dividing heterokaryons, and found that previously silent genes could be activated.[1][2][3][4][10] As a result, human keratinocytes, hepatocytes and fibroblasts expressed muscle genes that they normally never would. This body of work showed that the differentiated state requires continuous regulation and that a shift in the stoichiometry of trans-acting regulators induces nuclear reprogramming to another differentiated state.[11][12][13] Her discoveries fostered the development of the field of stem cell biology and regenerative medicine.[14]

Blau characterized muscle stem cells and showed they are dysfunctional in aging and in muscular dystrophy.[15][16][17][18] She showed that stem cells lose their regenerative potential when grown in traditional plastic dishes and overcame this limitation by fabricating bioengineered microenvironments that mimic crucial stem cell niche and tissue properties.[19][20][21] She has applied this approach to identify molecules that rejuvenate the function of the aged stem cell population and enhance muscle regeneration.[17]

Blau showed that telomere dysfunction in conjunction with dystrophin deficiency plays a central role in the skeletal muscle wasting and fatal cardiomyopathy characteristic of Duchenne muscular dystrophy.[16][15] Her lab's novel technologies enable rapid, transient and robust elongation of telomeres to overcome cellular dysfunction due to short telomeres, which have translational applications.[22][23]

Dr. Blau's lab applied evolutionary lessons from newts and salamanders that regenerate limbs to identify genes that constitute barriers to regeneration.[24][25] By transiently alleviating these brakes on the cell cycle, post-mitotic cells are induced to divide, reconstituting a regenerative cell source.[26][27]

A hallmark of Blau's research is the development and application of novel technologies. Her discovery of β-galactosidase complementation is widely used in drug discovery.[28][29][30][31][32][33][34] Non-invasive bioluminescence imaging enables highly sensitive temporal and spatial resolution of muscle stem cell regenerative function in vivo.[17][19][35] Using single cell lineage tracking and the Baxter algorithms her lab developed, cell morphology, movement, cell-cell interactions, division behavior and gene expression can be dynamically monitored, resolving the cellular basis for population changes, in response to pharmacologic interventions.[19][36][37][38] She has eight issued US patents.[39]

Current research

Blau's ongoing research focuses on cellular reprogramming, therapeutic interventions to enhance stem cell function in muscle regeneration, and cell rejuvenation strategies.

Honors

Along her professional career, among other honors, Professor Blau has won the following distinctions:

Public service and advisory committees

Helen Blau has contributed to multiple national and international committees and boards. She served on the Congressional Liaison Committee for Public Policy for the American Society for Cell Biology. At NIH she served on the (RAC) Oversight Committee of Gene Therapy (created by Harold Varmus) and as a member of the Council of the National Institute on Aging. She has been a member of the Harvard Board of Overseers and the Board of Directors of the American Society of Gene Therapy and the Council of the National Academy of Medicine of the National Academy of Sciences. She has advised the Conseil Stratégique de l’Association Française contre les Myopathies (AFM) and served on the Scientific Advisory Boards of the Helmsley Trust and the Ellison Medical Foundation. She currently serves on the Pew Charitable Trust Scholars Advisory Committee and the Council of the American Academy of Arts and Sciences.

Personal life

Blau was born in England, spent her early childhood in the U.S. and then lived in Europe until she moved to the United States for graduate school. She speaks French and German. Her father, George E. Blau, was Chief historian for the U.S. Government in Europe and her mother Gertrud M. Blau was an instructor of comparative literature at Heidelberg University and they strongly encouraged Helen and her sister Professor Eve Blau, now on the faculty at Harvard University, to pursue higher education. She is married to Professor David Spiegel, a research psychiatrist at Stanford University, and they have two children, Daniel Blau Spiegel,[43] an architect, and Julia Blau Spiegel,[44] a lawyer. Professor Blau and her husband are avid scuba divers and skiers.

References
  1. Blau, H. M.; Webster, C.; Pavlath, G. K. (1983-08-01). "Defective myoblasts identified in Duchenne muscular dystrophy". Proceedings of the National Academy of Sciences of the United States of America. 80 (15): 4856–4860. Bibcode:1983PNAS...80.4856B. doi:10.1073/pnas.80.15.4856. ISSN 0027-8424. PMC 384144. PMID 6576361.
  2. Chiu, C. P.; Blau, H. M. (1984-07-01). "Reprogramming cell differentiation in the absence of DNA synthesis". Cell. 37 (3): 879–887. doi:10.1016/0092-8674(84)90423-9. ISSN 0092-8674. PMID 6744415. S2CID 23400566.
  3. Chiu, C (1985). "5-azacytidine permits gene activation in a previously noninducible cell type". Cell. 40 (2): 417–24. doi:10.1016/0092-8674(85)90155-2. PMID 2578323. S2CID 43679574.
  4. Blau, H. M.; Pavlath, G. K.; Hardeman, E. C.; Chiu, C. P.; Silberstein, L.; Webster, S. G.; Miller, S. C.; Webster, C. (1985-11-15). "Plasticity of the differentiated state". Science. 230 (4727): 758–766. Bibcode:1985Sci...230..758B. doi:10.1126/science.2414846. ISSN 0036-8075. PMID 2414846. S2CID 27968534.
  5. Search Results for author Blau HM on PubMed.
  6. "Blau Lab". web.stanford.edu.
  7. Ningthoujam, Debananda S. Footprints of Pioneer Scientists-58: Helen M. Blau Archived 2014-02-22 at the Wayback Machine. Manipur Times. Access date: September 5, 2015
  8. Blau, Helen M (2012). "Redefining differentiation: Reshaping our ends". Nature Cell Biology. 14 (6): 558. doi:10.1038/ncb2506. PMID 22643873. S2CID 9919350.
  9. Brian K. Kennedy, PhD, in conversation with Helen M. Blau, PhD, Director, Baxter Laboratory for Stem Cell Biology, retrieved 2015-09-06
  10. Pomerantz, Jason H.; Mukherjee, Semanti; Palermo, Adam T.; Blau, Helen M. (2009-04-01). "Reprogramming to a muscle fate by fusion recapitulates differentiation". Journal of Cell Science. 122 (Pt 7): 1045–1053. doi:10.1242/jcs.041376. ISSN 0021-9533. PMC 2720934. PMID 19295131.
  11. Blau, H. M.; Baltimore, D. (1991). "Differentiation requires continuous regulation" (PDF). The Journal of Cell Biology. 112 (5): 781–783. doi:10.1083/jcb.112.5.781. ISSN 0021-9525. PMC 2288865. PMID 1999456.
  12. Blau, H. M. (1992). "Differentiation requires continuous active control". Annual Review of Biochemistry. 61: 1213–1230. doi:10.1146/annurev.bi.61.070192.010025. ISSN 0066-4154. PMID 1497309. S2CID 21198451.
  13. Blau, H. M.; Dhawan, J.; Pavlath, G. K. (1993-08-01). "Myoblasts in pattern formation and gene therapy". Trends in Genetics. 9 (8): 269–274. doi:10.1016/0168-9525(93)90012-7. ISSN 0168-9525. PMID 8379006.
  14. Yamanaka, Shinya; Blau, Helen M. (2010-06-10). "Nuclear reprogramming to a pluripotent state by three approaches". Nature. 465 (7299): 704–712. Bibcode:2010Natur.465..704Y. doi:10.1038/nature09229. ISSN 1476-4687. PMC 2901154. PMID 20535199.
  15. Sacco, Alessandra; Mourkioti, Foteini; Tran, Rose; Choi, Jinkuk; Llewellyn, Michael; Kraft, Peggy; Shkreli, Marina; Delp, Scott; Pomerantz, Jason H. (2010-12-23). "Short telomeres and stem cell exhaustion model Duchenne muscular dystrophy in mdx/mTR mice". Cell. 143 (7): 1059–1071. doi:10.1016/j.cell.2010.11.039. ISSN 1097-4172. PMC 3025608. PMID 21145579.
  16. Mourkioti, Foteini; Kustan, Jackie; Kraft, Peggy; Day, John W.; Zhao, Ming-Ming; Kost-Alimova, Maria; Protopopov, Alexei; DePinho, Ronald A.; Bernstein, Daniel (2013-08-01). "Role of telomere dysfunction in cardiac failure in Duchenne muscular dystrophy". Nature Cell Biology. 15 (8): 895–904. doi:10.1038/ncb2790. ISSN 1476-4679. PMC 3774175. PMID 23831727.
  17. Cosgrove, Benjamin D.; Gilbert, Penney M.; Porpiglia, Ermelinda; Mourkioti, Foteini; Lee, Steven P.; Corbel, Stephane Y.; Llewellyn, Michael E.; Delp, Scott L.; Blau, Helen M. (2014-03-01). "Rejuvenation of the muscle stem cell population restores strength to injured aged muscles". Nature Medicine. 20 (3): 255–264. doi:10.1038/nm.3464. ISSN 1546-170X. PMC 3949152. PMID 24531378.
  18. Blau, Helen M.; Cosgrove, Benjamin D.; Ho, Andrew T. V. (2015-08-06). "The central role of muscle stem cells in regenerative failure with aging". Nature Medicine. 21 (8): 854–862. doi:10.1038/nm.3918. ISSN 1546-170X. PMC 4731230. PMID 26248268.
  19. Gilbert, P. M.; Havenstrite, K. L.; Magnusson, K. E. G.; Sacco, A.; Leonardi, N. A.; Kraft, P.; Nguyen, N. K.; Thrun, S.; Lutolf, M. P. (2010-08-27). "Substrate elasticity regulates skeletal muscle stem cell self-renewal in culture". Science. 329 (5995): 1078–1081. Bibcode:2010Sci...329.1078G. doi:10.1126/science.1191035. ISSN 1095-9203. PMC 2929271. PMID 20647425.
  20. Gilbert, Penney M.; Corbel, Stephane; Doyonnas, Regis; Havenstrite, Karen; Magnusson, Klas E. G.; Blau, Helen M. (2012-04-01). "A single cell bioengineering approach to elucidate mechanisms of adult stem cell self-renewal". Integrative Biology. 4 (4): 360–367. doi:10.1039/c2ib00148a. ISSN 1757-9708. PMC 3325106. PMID 22327505.
  21. Lutolf, Matthias P.; Gilbert, Penney M.; Blau, Helen M. (2009-11-26). "Designing materials to direct stem-cell fate". Nature. 462 (7272): 433–441. Bibcode:2009Natur.462..433L. doi:10.1038/nature08602. ISSN 1476-4687. PMC 2908011. PMID 19940913.
  22. Ramunas, John; Yakubov, Eduard; Brady, Jennifer J.; Corbel, Stéphane Y.; Holbrook, Colin; Brandt, Moritz; Stein, Jonathan; Santiago, Juan G.; Cooke, John P. (2015-05-01). "Transient delivery of modified mRNA encoding TERT rapidly extends telomeres in human cells". FASEB Journal. 29 (5): 1930–1939. doi:10.1096/fj.14-259531. ISSN 1530-6860. PMC 4415018. PMID 25614443.
  23. Park, Alice. "The Cure for Aging". TIME.com. Retrieved 2015-09-06.
  24. Blau, Helen M.; Pomerantz, Jason H. (2011-01-05). "Re"evolutionary" regenerative medicine". JAMA. 305 (1): 87–88. doi:10.1001/jama.2010.1938. ISSN 1538-3598. PMC 3105469. PMID 21177496.
  25. Winslow, Gautam Naik And Ron. "New Clues on Regrowing Tissue". Wall Street Journal. ISSN 0099-9660. Retrieved 2015-09-06.
  26. Pajcini, Kostandin V.; Corbel, Stephane Y.; Sage, Julien; Pomerantz, Jason H.; Blau, Helen M. (2010-08-06). "Transient inactivation of Rb and ARF yields regenerative cells from postmitotic mammalian muscle". Cell Stem Cell. 7 (2): 198–213. doi:10.1016/j.stem.2010.05.022. ISSN 1875-9777. PMC 2919350. PMID 20682446.
  27. Pomerantz, Jason H.; Blau, Helen M. (2013-06-01). "Tumor suppressors: enhancers or suppressors of regeneration?". Development. 140 (12): 2502–2512. doi:10.1242/dev.084210. ISSN 1477-9129. PMC 3666379. PMID 23715544.
  28. Bit-Wizards. "Solutions for Target-based & Phenotypic Drug Discovery - DiscoveRx". www.discoverx.com. Retrieved 2015-09-06.
  29. Wehrman, Thomas S.; von Degenfeld, Georges; Krutzik, Peter O.; Nolan, Garry P.; Blau, Helen M. (2006-04-01). "Luminescent imaging of beta-galactosidase activity in living subjects using sequential reporter-enzyme luminescence". Nature Methods. 3 (4): 295–301. doi:10.1038/nmeth868. ISSN 1548-7091. PMID 16554835. S2CID 30672152.
  30. von Degenfeld, Georges; Wehrman, Tom S.; Hammer, Mark M.; Blau, Helen M. (2007-12-01). "A universal technology for monitoring G-protein-coupled receptor activation in vitro and noninvasively in live animals". FASEB Journal. 21 (14): 3819–3826. doi:10.1096/fj.07-9597com. ISSN 1530-6860. PMID 17942828. S2CID 21768434.
  31. von Degenfeld, Georges; Wehrman, Tom S.; Blau, Helen M. (2009-01-01). "Imaging β-Galactosidase Activity in Vivo Using Sequential Reporter-Enzyme Luminescence". Bioluminescence. Methods in Molecular Biology. Vol. 574. pp. 249–259. doi:10.1007/978-1-60327-321-3_20. ISBN 978-1-60327-320-6. ISSN 1940-6029. PMC 2902154. PMID 19685314.
  32. Hammer, Mark M.; Wehrman, Tom S.; Blau, Helen M. (2007-12-01). "A novel enzyme complementation-based assay for monitoring G-protein-coupled receptor internalization". FASEB Journal. 21 (14): 3827–3834. doi:10.1096/fj.07-8777com. ISSN 1530-6860. PMID 17942829. S2CID 221750367.
  33. Wehrman, T. S.; Raab, W. J.; Casipit, C. L.; Doyonnas, R.; Pomerantz, J. H.; Blau, H. M. (2006-12-12). "A system for quantifying dynamic protein interactions defines a role for Herceptin in modulating ErbB2 interactions". Proceedings of the National Academy of Sciences of the United States of America. 103 (50): 19063–19068. Bibcode:2006PNAS..10319063W. doi:10.1073/pnas.0605218103. ISSN 0027-8424. PMC 1748177. PMID 17148612.
  34. Wehrman, Tom S.; Casipit, Clayton L.; Gewertz, Nevin M.; Blau, Helen M. (2005-07-01). "Enzymatic detection of protein translocation". Nature Methods. 2 (7): 521–527. doi:10.1038/nmeth771. ISSN 1548-7091. PMID 15973423. S2CID 25551558.
  35. Sacco, Alessandra; Doyonnas, Regis; Kraft, Peggy; Vitorovic, Stefan; Blau, Helen M. (2008-11-27). "Self-renewal and expansion of single transplanted muscle stem cells". Nature. 456 (7221): 502–506. Bibcode:2008Natur.456..502S. doi:10.1038/nature07384. ISSN 1476-4687. PMC 2919355. PMID 18806774.
  36. Magnusson, Klas E G; Jalden, Joakim; Gilbert, Penney M; Blau, Helen M (2015). "Global Linking of Cell Tracks Using the Viterbi Algorithm". IEEE Transactions on Medical Imaging. 34 (4): 911–29. doi:10.1109/TMI.2014.2370951. PMC 4765504. PMID 25415983.
  37. Chenouard, Nicolas; Smal, Ihor; de Chaumont, Fabrice; Maška, Martin; Sbalzarini, Ivo F.; Gong, Yuanhao; Cardinale, Janick; Carthel, Craig; Coraluppi, Stefano (2014-03-01). "Objective comparison of particle tracking methods". Nature Methods. 11 (3): 281–289. doi:10.1038/nmeth.2808. ISSN 1548-7105. PMC 4131736. PMID 24441936.
  38. Maška, Martin; Ulman, Vladimír; Svoboda, David; Matula, Pavel; Matula, Petr; Ederra, Cristina; Urbiola, Ainhoa; España, Tomás; Venkatesan, Subramanian (2014-06-01). "A benchmark for comparison of cell tracking algorithms". Bioinformatics. 30 (11): 1609–1617. doi:10.1093/bioinformatics/btu080. ISSN 1367-4811. PMC 4029039. PMID 24526711.
  39. "Google Patent Search - Inventor: Helen M. Blau". www.google.com. Retrieved 2018-02-24.
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