Lucy Shapiro

Lucy Shapiro (born July 16, 1940, New York City) is an American developmental biologist. She is a professor of Developmental Biology at the Stanford University School of Medicine. She is the Virginia and D.K. Ludwig Professor of Cancer Research and the director of the Beckman Center for Molecular and Genetic Medicine.[1]

Lucy Shapiro
Born (1940-07-16) July 16, 1940
NationalityAmerican
CitizenshipU.S.
Alma materBrooklyn College; Albert Einstein College of Medicine
Known forIdentification of the molecular mechanisms of cell cycle regulation and asymmetric cell division, and characterization of the systems biology of bacterial development.
SpouseHarley McAdams
AwardsSelman A. Waksman Award in Microbiology (2005)
Gairdner Foundation International Award (2009)
National Medal of Science (2011)
Louisa Gross Horwitz Prize (2012)
Pearl Meister Greengard Prize (2014)
Scientific career
FieldsDevelopmental biology; microbial genetics; bacterial cell biology
InstitutionsAlbert Einstein College of Medicine, Stanford University
Websitehttp://shapirolab.stanford.edu
External video
video icon Lucy Shapiro – 2011 National Medal of Science
video icon Part 1: Dynamics of the Bacterial Chromosome, Lucy Shapiro (Stanford University)
video icon Part 2: Escalating Infectious Disease Threat, Lucy Shapiro (Stanford University)

Shapiro founded a new field in developmental biology, using microorganisms to examine fundamental questions in developmental biology. Her work has furthered understanding of the basis of stem cell function and the generation of biological diversity.[2] Her ideas have revolutionized understanding of bacterial genetic networks and helped researchers to develop novel drugs to fight antibiotic resistance and emerging infectious diseases.[3] In 2013, Shapiro was presented with the 2011 National Medal of Science.[3][4] for "her pioneering discovery that the bacterial cell is controlled by an integrated genetic circuit functioning in time and space that serves as a systems engineering paradigm underlying cell differentiation and ultimately the generation of diversity in all organisms."

Early life and education

Lucy Shapiro was born in Brooklyn, New York City, the eldest of three daughters. Her mother was an elementary school teacher and her father, a Ukrainian immigrant. She attended New York City's High School of Music and Arts with a major in Fine Arts.[5]

Shapiro enrolled in Brooklyn College with a double major in Fine Arts and Biology and the intention of becoming a medical illustrator.[6][7] As part of an experimental honors program she was able to design her own curriculum. With the encouragement of Theodore Shedlovsky,[8] she talked her way into an honors organic chemistry class. There her spatial and scientific interests reinforced each other as she visualized the spatial properties of organic molecules in three dimensions.[9] She received her A.B. in Fine Arts and Biology from Brooklyn College in 1962.[8]

In fall 1962 Shapiro was hired as a lab technician by J. Thomas August and Jerard Hurwitz in the department of microbiology at the New York University (NYU) school of medicine.[8] Hurwitz was a co-discoverer of DNA-dependent RNA polymerase.[10] Shapiro was given the task of looking for RNA-dependent RNA polymerase using F2 RNA phage from Norton Zinder. She was successful in detecting the activity of an enzyme copying RNA. In 1963 Shapiro became a graduate student at NYU with Tom August as her advisor. The department subsequently joined the newly created department of molecular biology at the Albert Einstein College of Medicine. Shapiro also attended summer courses at Cold Spring Harbor Laboratory (CSHL) on Long Island.[8][6] Shapiro earned her Ph.D. at the Albert Einstein College of Medicine in 1966, with the thesis Replication of bacteriophage RNA.[11][12]

Shapiro has published reflections on her early days in Brooklyn and on her life in science in the Journal of Biological Chemistry[13] and in the Annual Review of Genetics.[8]

Work

Academic positions

Shapiro initially planned to do postdoctoral work elsewhere, but was offered a faculty position at Einstein by Bernard Horecker. Horecker proposed that she take three months to think about fundamental questions and the direction of her future research life. Shapiro identified positional information as a key research area, asking how spatial information is genetically encoded and translated, to create the three-dimensional organization of a cell[6] and to form different daughter cells through cell division. With how a cell organizes its three-dimensional structure as her focus,[8] Shapiro launched her own lab at Einstein in 1967.[14]

Shapiro remained at the Albert Einstein College of Medicine from 1967–1986, as assistant professor, associate professor, and professor. In 1977, she became chair of the department of molecular biology[8] and in 1981, director of Einstein's division of biological sciences.[14][6] In 1983,[15] she was named to the Lola and Saul Kramer Endowed Chair in Molecular Biology, Albert Einstein College of Medicine, NYC.[16]

From 1986–1989, Shapiro served as the Higgins Professor and Chair of Microbiology at the College of Physicians and Surgeons of Columbia University.[16][8]

In 1989, Shapiro became a professor and the founding chair of the department of developmental biology at Stanford University School of Medicine, Stanford, California.[8] She was the Joseph D. Grant Professor in the school of medicine from 1989–1998,[17] before becoming the Virginia and D.K. Ludwig Professor of Cancer Research in 1998.[17] In 2001 Shapiro became the director of the Beckman Center for Molecular and Genetic Medicine at Stanford University School of Medicine.[8]

'If you are confident in what you are talking about, and your science is excellent, there is no need to be intimidated by anyone,' says Shapiro. 'This is particularly important for women in science.'[9]

Industry positions

  • 1993–2000: Director, Silicon Graphics, Inc.
  • 1993–2000: Director, SmithKlineBeecham[18]
  • 2000–2006: Director, Glaxo Smith Kline
  • 2002: Founded Anacor Pharmaceuticals, Inc. with Dr. Stephen Benkovic, Penn State University, and Dr. Harley McAdams, Stanford University School of Medicine.[11]
  • 2002: Director, Anacor Pharmaceuticals, Inc.[11]
  • 2008–2012: Director, GenProbe, Inc.[19]
  • 2012: Director, Pacific BioSciences, Inc.[20][21]
  • 2015: Founded Boragen, LLC with Stephen Benkovic, Gerry Fink and Paul Schimmel[22]
  • 2021: Director, 5Metis, Inc.[8]

Achievements

After six months as a postdoctoral student at Albert Einstein College of Medicine, Shapiro was asked to join the faculty and establish her own lab. Asked what she most wanted to work on, Shapiro decided that she was fascinated by how a one-dimensional genetic code, DNA, could be translated into three-dimensional organisms.[23][24] Shapiro wanted to go beyond test-tube studies of extracted cell contents, and examine the three-dimensional structure and behavior of actual living cells.[5] "I found the simplest organism I could, and set out to learn how the multiple components of a living cell work together."[24] She selected a single-celled organism, Caulobacter crescentus, and began attempting to identify the specific biological processes controlling the cell's cycle.[2]

What she and her students discovered overturned accepted beliefs about bacterial cell biology. In each cell cycle, Caulobacter divides asymmetrically into two daughters. One, the swarmer cell, has a tail-like flagellum that helps it swim; the other daughter has a stalk which anchors it to a surface. Swarmer cells become stalked cells after a short period of motility. Chromosome replication and cell division only occur in stalked cells. Rather than containing an evenly dispersed mixture of proteins, the single celled Caulobacter resembles a highly organized factory, with specific "machinery" regulating each step in the cell cycle to ensure that changes occur at developmentally appropriate times. DNA is copied once per cycle by a particular group of molecules. Once a single DNA copy is placed in each half of the cell, other mechanisms constricts the cell's middle to separate it into two daughters.[5] Shapiro was the first researcher to show that bacterial DNA replication occurs in a spatially organized way and that cell division is dependent on this spatial organization.[25]

By the late 1990s, Shapiro and graduate student Michael Laub were able to study the genetic basis of cell cycle progression and consequently the identification of three regulatory proteins, DnaA, GcrA, and CtrA, which controlled complex temporal and spatial behaviors affecting large numbers of genes. With Dickon Alley and Janine Maddock, she showed that chemoreceptor proteins occupy specific areas within the cell. Shapiro and Christine Jacobs-Wagner as well as Janine Maddock showed that signaling phosphokinases also had specific positions at the cell poles. In 2004, using time-lapse microscopy and fluorescent tags, Shapiro demonstrated that chromosomal regions are duplicated in both an orderly and a location-specific manner, involving "a much higher degree of spatial organization than previously thought".[5]

By studying the regulation of the cell cycle, asymmetric cell division, and cellular differentiation, Shapiro's work has led to a much deeper understanding of the genetic and molecular processes that cause identical bacterial cells to split into different cell types. These are basic processes that underlie all life, from single-cell bacteria to multi-cellular organisms.[2] The process of the Caulobacter cell cycle also show similarities to stem cell division, in which two distinct cells arise, one of which differs from the parent cell while the other does not.[5]

Since 1995, her work with Harley McAdams has applied insights and analysis techniques from the field of electrical circuitry to bacteria, to examine how biological systems work as a whole.[26] Genome-based computational modelling, in particular, the examination of regulatory networks, is becoming increasingly important to systems biology.[27] Examining the cell cycle control logic of Caulobacter as a state machine leads to understanding of bacterial cell cycle regulation as a whole cell phenomenon.[28]

Biotechnology

In 2002, Shapiro founded Anacor Pharmaceuticals with physicist and developmental biologist Harley McAdams and chemist Stephen Benkovic of Pennsylvania State University.[11] to design and develop new types of antibiotics and antifungals.[3] They have developed a novel class of small molecules involving a Boron atom, and produced one of two new antifungal agents to be created in the last 25 years.,[5] approved by the FDA as a treatment for toe nail fungus, Kerydin. A second drug, Crisaborole, was developed to treat atopic dermatitis. In 2015, Shapiro, Benkovic, Fink and Schimmel founded Boragen, LLC to use the boron containing library for crop protection.[22]

Advocacy

Shapiro has advised both the Clinton administration and the second Bush administration. She belongs to the Center for International Security and Cooperation at the Freeman Spogli Institute for International Studies at Stanford University.[3] She is particularly concerned about the potential impact of emerging infectious diseases.[29] There are a number of issues that make infectious diseases a particularly significant concern. One issue is the development of antibiotic-resistant microbes, which have been emerging as a result of over-use of antibiotics since the 1950s. Shapiro is involved in development of drugs that will attack both a particular bacteria and its mechanisms of drug resistance, to prevent drug-resistant strains from developing. Another concern is the introduction of bacteria into previously unexposed populations, due to increased travel, population expansion into previously unexplored areas, and climate change.[30] This includes the development of zoönotic diseases which travel from one species to another, such as influenza.[31] To address either naturally occurring or intentionally developed biological threats, it is essential to understand the mechanisms involved internally in cells and in populations of cells in their environments. Shapiro emphasizes the importance of understanding the complexity of living systems, and the need to be aware that interventions may have unexpected consequences.[30]

Awards and honors

References

  1. "Biographical Sketch: Lucy Shapiro, Ph.D. – National Institute of General Medical Sciences". Nigms.nih.gov. 2011-12-27. Archived from the original on 2009-05-08. Retrieved 2013-03-30.
  2. "Biographical Sketch: Lucy Shapiro, Ph.D." National Institute of General Medical Sciences. U.S. Department of Health and Human Services. 2002.
  3. Conger, Krista (January 28, 2013). "Lucy Shapiro to be awarded National Medal of Science". Stanford Medicine News Center. Retrieved 14 May 2015.
  4. Stober, Dan (2013-02-01). "Obama presents the National Medal of Science to Stanford's Lucy Shapiro and Sidney Drell". News.stanford.edu. Retrieved 2013-03-30.
  5. "2014 Lucy Shapiro". Greengard Prize. 2014. Archived from the original on 12 August 2017. Retrieved 14 May 2015.
  6. Neill, Ushma S. (August 1, 2019). "A conversation with Lucy Shapiro". The Journal of Clinical Investigation. 129 (8): 2981–2982. doi:10.1172/JCI131492. ISSN 0021-9738. PMC 6668687. PMID 31368904.
  7. Azvolinsky, Anna (Aug 1, 2018). "The Cell's Integrated Circuit: A Profile of Lucy Shapiro". The Scientist Magazine. Retrieved 8 December 2022.
  8. Shapiro, Lucy (30 November 2022). "A Half Century Defining the Logic of Cellular Life". Annual Review of Genetics. 56 (1): 1–15. doi:10.1146/annurev-genet-071719-021436. ISSN 0066-4197. PMID 36449355. S2CID 254093699. Retrieved 7 December 2022.
  9. Hannon, Patricia (27 August 2018). "Celebrating Lucy Shapiro, from artist to award-winning developmental biologist". Scope. Retrieved 8 December 2022.
  10. Hurwitz, Jerard (30 December 2005). "The Discovery of RNA Polymerase". Journal of Biological Chemistry. 280 (52): 42477–42485. doi:10.1074/jbc.X500006200. ISSN 0021-9258. PMID 16230341. Retrieved 8 December 2022.
  11. "Lucy Shapiro". National Science and Technology Medals Foundation. Retrieved 7 December 2022.
  12. Shapiro, L. (1966). Replication of bacteriophage RNA (Ph.D. Thesis). New York City: Albert Einstein College of Medicine.
  13. Shapiro, L. (24 September 2012). "Life in a Three-dimensional Grid". Journal of Biological Chemistry. 287 (45): 38289–38294. doi:10.1074/jbc.X112.422337. PMC 3488097. PMID 23007401.
  14. Conger, Krista (1 April 2009). "Biologist Lucy Shapiro nabs $100,000 Canadian prize". Stanford University. Retrieved 8 December 2022.
  15. "Lucy Shapiro". Stanford University. Retrieved 8 December 2022.
  16. "Lucy Shapiro". Gairdner Foundation. Retrieved 7 December 2022.
  17. "Endowed chairs for Shapiro, Holmes: 5/13/98". Stanford Report. Stanford University. May 13, 1998. Retrieved 7 December 2022.
  18. "First Annual FTSE Female Index". HRM Guide. 7 November 2000. Retrieved 15 May 2015.
  19. "Lucy Shapiro, Ph.D., Elected to Gen-Probe Board of Directors". PR Newswire. May 19, 2008. Retrieved 15 May 2015.
  20. "Pacific Biosciences Appoints Lucy Shapiro, Ph.D. to Board of Directors". Pacific Biosciences News Release. September 12, 2012. Archived from the original on August 18, 2017. Retrieved May 15, 2015.
  21. "Pacific Biosciences of California Inc.: Lucy Shapiro". Wall Street Journal. Retrieved 15 May 2015.
  22. "Fresh from raising $2M, RTP startup Boragen lands R&D deal for animal health". WRAL TechWire. 7 January 2020. Retrieved 7 December 2022.
  23. "Lucy Shapiro, Ph.D." The Rockefeller University. Retrieved 7 December 2022.
  24. Conger, Krista (March 31, 2009). "Top Canadian Prize Goes to Stanford Scientist Lucy Shapiro for Bringing Cell Biology into Three Dimensions". Business Wire. Retrieved 14 May 2015.
  25. Streich, Elizabeth (September 24, 2012). "Horwitz Prize Awarded for the Discovery of Bacterial Cell Structure". Columbia University Medical Center Newsroom. Retrieved 15 May 2015.
  26. McAdams, H.; Shapiro, L. (4 August 1995). "Circuit simulation of genetic networks". Science. 269 (5224): 650–656. Bibcode:1995Sci...269..650M. doi:10.1126/science.7624793. PMID 7624793.
  27. Moody, Glyn (2004). Digital code of life : how bioinformatics is revolutionizing science, medicine, and business. Hoboken, NJ: Wiley. p. 308. ISBN 0471327883. Retrieved 15 May 2015.
  28. McAdams, Harley H.; Shapiro, Lucy (December 2009). "System-level design of bacterial cell cycle control". FEBS Letters. 583 (24): 3984–3991. doi:10.1016/j.febslet.2009.09.030. PMC 2795017. PMID 19766635.
  29. White, Tracie (June 15, 2015). "Use science to make world a better place, graduates told". Stanford Medicine News Center. Retrieved 4 August 2015.
  30. Kuhn, Robert Lawrence (2007). Closer to truth : science, meaning and the future. Westport, Conn.: Praeger. ISBN 978-0275993894. Retrieved 15 May 2015.
  31. Quammen, David (2013). Spillover : animal infections and the next human pandemic (Norton pbk. ed.). New York: W.W. Norton. ISBN 978-0393346619.
  32. "Convocation for Conferring Degrees Virtual Ceremony Thursday, June 11, 2020" (PDF). The Rockefeller University. Retrieved 7 December 2022.
  33. University, Carnegie Mellon. "Lucy Shapiro – University Lecture Series – Carnegie Mellon University". Carnegie Mellon University.
  34. Adams, Amy (8 February 2017). "Stanford faculty named in first cohort of Chan Zuckerberg Biohub investigators". Stanford News. Retrieved 7 December 2022.
  35. "Alumna and Alumnus of the Year". Brooklyn College. Retrieved 7 December 2022.
  36. "Lucy Shapiro, Ph.D. Awarded the 2014 Pearl Meister Greengard Prize". Pearl Meister Greengard Prize. 2014. Retrieved 14 May 2015.
  37. "WICB Award Recipients Announced". ASCB: American Society for Cell Biology. 2013. Retrieved 15 May 2015.
  38. "Horwitz Prize Awarded for the Discovery of Bacterial Cell Structure". Columbia University Irving Medical Center. 24 September 2012. Retrieved 8 December 2022.
  39. "Lucy Shapiro". Stanford School of Medicine. Retrieved 14 May 2015.
  40. Richter, Ruthann (October 7, 2012). "Dean's Medals go to actress, scientist, oncologist and foundation". News Center (in Samoan). Retrieved 7 December 2022.
  41. "Commencement 2010" (PDF). Einstein. 2010. p. 49. Retrieved 7 December 2022.
  42. "American Society for Microbiology honors Lucy Shapiro". American Society for Microbiology. 2 March 2010. Retrieved 15 May 2015.
  43. "ASM Lifetime Achievement Award (sponsored by AbbVie) Past Laureates". ASM Society. Archived from the original on 5 March 2016. Retrieved 15 May 2015.
  44. Wiecek, Andrew S. (May 31, 2009). "2009 Canada Gairdner International Awards announced". BioTechniques. Archived from the original on 18 August 2017. Retrieved 15 May 2015.
  45. "2009 Gairdner Foundation Lectures: Dr. Lucy Shapiro". Cumming School of Medicine. Archived from the original on 18 May 2015. Retrieved 15 May 2015.
  46. "Selman A. Waksman Award in Microbiology". National Academy of Sciences. Retrieved 15 May 2015.
  47. American Philosophical Society (2003). "Members Elected in April 2003" (PDF). News from Philosophical Hall. 7 (2): 10. Archived from the original (PDF) on 2014-11-17. Retrieved 2015-05-15.
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