Lucy Shapiro

• 1967-1986: Assistant Professor, Associate 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 Biology, 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.

• 1993-2000: Director, Silicon Graphics, Inc.
• 1993-2000: Director, SmithKlineBeecham[8]
• 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.[9]
• 2002: Director, Anacor Pharmaceuticals, Inc.
• 2012: Director, Pacific BioSciences, Inc.[10][11]
• 2015: Founded Boragen, LLC with Stephen Benkovic, Gerry Fink and Paul Schimmel
• 2015: Director, Boragen, LLC

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.[6] 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."[6] 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.[12]

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".[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.[13] Genome-based computational modelling, in particular, the examination of regulatory networks, is becoming increasingly important to systems biology.[14] 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.[15]

In 2002, Shapiro founded Anacor Pharmaceuticals with her husband, physicist and developmental biologist Harley McAdams and chemist Stephen Benkovic of Pennsylvania State University.[16] Located in Palo Alto, the biotechnology company's purpose is 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, 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.

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.[17] 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.[18] This includes the development of zoönotic diseases which travel from one species to another, such as influenza.[19] 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.[18]