Lucy Shapiro

Lucy Shapiro
Born	(1940-07-16) July 16, 1940 New York City, New York
Residence	California, United States
Citizenship	U.S.
Nationality	American
Fields	Developmental biology; microbial genetics; bacterial cell biology
Institutions	Stanford University
Alma mater	Brooklyn College; Albert Einstein College of Medicine
Known for	Identification of the molecular mechanisms of cell cycle regulation and asymmetric cell division, and characterization of the systems biology of bacterial development.
Notable awards	Selman 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)
Spouse	Harley McAdams
Website http://shapirolab.stanford.edu

External video
Lucy Shapiro - 2011 National Medal of Science
Part 1: Dynamics of the Bacterial Chromosome, Lucy Shapiro (Stanford University)
Part 2: Escalating Infectious Disease Threat, Lucy Shapiro (Stanford University)

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 Ludwig Professor of Cancer Research and the director of the Beckman Center for Molecular and Genetic Medicine. She 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. Her ideas have revolutionized understanding of bacterial genetic networks and helped researchers to develop novel drugs to fight antibiotic resistance and emerging infectious diseases. In 2013, Dr. Shapiro was presented with the 2011 National Medal of Science. 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 New York City and grew up in Brooklyn, where she attended primary school in New York Public School 169. She then attended New York City's High School of Music and Arts (the precursor school to the Fiorello H. LaGuardia High School of Music & Art and Performing Arts) with a major in Fine Arts.

She went on to major in both fine arts and biology, earning her A.B. in Fine Arts and Biology from Brooklyn College in 1962. She wrote her undergraduate thesis on the Florentine poet Dante, exploring on why he chose to write in the vernacular rather than in Latin. After professor Theodore Shedlovsky at Rockefeller University convinced her to take an organic chemistry course, she became interested in both the visual aspects and the intellectual rigor of organic chemistry, and changed her course of study. She received her PhD in Molecular Biology in 1966 from Albert Einstein College of Medicine, where she worked with J. Thomas August and Jerard Hurwitz on the first RNA-dependent RNA polymerase.

Dr. Shapiro has published a reflection on her early days in Brooklyn and on her life in science in the Journal of Biological Chemistry.

Work

Academic positions

• 1967-1986 Asst. Professor, Assoc. Professor, and Professor Albert Einstein College of Medicine, NYC.
• 1977-1986 Chair, Department of Molecular Biology, Albert Einstein College of Medicine, NYC.
• 1981-1986 Director, Div. of Biological Sciences, Albert Einstein College of Medicine, NYC.
• 1983-1986 Lola and Saul Kramer Endowed Chair in Molecular Biology, Albert Einstein College of Medicine, NYC.
• 1986-1989 Higgens Professor of Microbiology and Chairman Department of Microbiology, Columbia University College of Physicians and Surgeons, NYC.
• 1989-1997 Founder and Chair Department of Developmental, Stanford University School of Medicine, Stanford, CA.
• 1989-1998 Joseph D. Grant Professor in the School of Medicine, Stanford University School of Medicine, Stanford, CA.
• 1989- Professor, Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA.
• 1998- Ludwig Professor of Cancer Research
• 2001- Director of the Beckman Center for Molecular and Genetic Medicine, Stanford University School of Medicine, Stanford, CA.

Industry Positions

• 1993-2000 Director, Silicon Graphics, Inc.
• 1993-2000 Director, SmithKlineBeecham
• 2002 Founded Anacor Pharmaceuticals, Inc. with Dr. Stephen Benkovic, Penn State University, and Dr. Harley McAdams, Stanford University School of Medicine.
• 2000-2006 Director, Glaxo Smith Kline
• 2008-2012 Director, GenProbe, Inc.
• 2002- Director, Anacor Pharmaceuticals, Inc.
• 2012- Director, Pacific BioSciences, Inc.
• 2015- Founded Boragen, LLC with Stephen Benkovic, Gerry Fink and Paul Schimmel
• 2015- Director, Boragen, LLC

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. Shapiro wanted to go beyond test-tube studies of extracted cell contents, and examine the three-dimensional structure and behavior of actual living cells. "I found the simplest organism I could, and set out to learn how the multiple components of a living cell work together." She selected a single-celled organism, Caulobacter crescentus, and began attempting to identify the specific biological processes controlling the cell's cycle.

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. 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.

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 was able to show that chemoreceptor proteins occupy specific areas within the cell. Shapiro and Christine Jacobs-Wagner as well as Janine Maddock showed that signaling phosphokinase also had specific positions at the cell poles. In 2005, using time-lapse microscopy and fluorescent tags, Shapiro was able to demonstrate 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".

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. 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.

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. Genome-based computational modelling, in particular, the examination of regulatory networks, is becoming increasingly important to systems biology. 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.

Biotechnology

In 2002, Shapiro founded Anacor Pharmaceuticals with physicist and developmental biologist Harley McAdams and chemist Stephen Benkovic of Pennsylvania State University. Located in Palo Alto, the biotechnology company's purpose is to design and develop new types of antibiotics and antifungals. 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., approved by the FDA as a treatment for toe nail fungus, Kerydin. A second drug, Crisaborole, for atopic dermatitis, had a successful phase III trial in 2015. In 2015, Shapiro, Benkovic, Fink and Schimmel founded Boragen, LLC to use the boron containing library for household model and agriculture.

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. She is particularly concerned about the potential impact of emerging infectious diseases. 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. This includes the development of zoönotic diseases which travel from one species to another, such as influenza. 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.

Awards and honors

• 2014, Pearl Meister Greengard Prize
• 2013, ASCB Women in Cell Biology Lifetime Achievement Award, American Society for Cell Biology
• 2012, Louisa Gross Horwitz Prize, with Richard Losick & Joe Lutkenhaus
• 2012, Dean's Medal, Stanford University School of Medicine
• 2011, National Medal of Science
• 2010, Distinguished Alumna, Albert Einstein College of Medicine
• 2010, Abbott Lifetime Achievement Award, American Society for Microbiology
• 2009, Canada Gairdner International Award with Richard Losick
• 2009, John Scott Legacy Medal and Premium, with Harley McAdams
• 2008, Hitchcock Professorship, UC Berkeley
• 2005, Selman A. Waksman Award in Microbiology
• 2003, Elected to the American Philosophical Society
• 1994, National Academy of Sciences
• 1993, American Academy of Microbiology
• 1992, American Academy of Arts and Sciences
• 1991, Institute of Medicine of the National Academy of Sciences
• 1983, Distinguished Alumna, Brooklyn College