Dr. Lansford is the recipient of the NASA Space Act Award for his contributions of Two-photon Microscope Imaging Spectrometer for Multiple Fluorecent Probes. Lansford has multiple patents for his systems and methods for monitoring cellular activity, as well as for his work in laser microscopy and imaging spectrometry. This development of a multispectral imager that allows the emission spectrum to be acquired from a single scan of specimen led to a multispectral detector based upon his invention, which is being sold by Zeiss.
Dr. Lansford’s scientific contributions, have been featured in the Pasadena Museum of California Art in an exhibit entitled, “Data + Art: Science and Art in the Age of Information,” as well and the San Francisco Exploratorium and California Science Center, where his Quail Developmental Atlas procured from basic research as a biology, math, and physics educational tool.
Changes in embryonic form and function
Seidl AH, Sanchez JT, Schecterson L, Tabor KM, Wang Y, Fraser SE, Kashima DT, Huss D, Poynter G, Lansford R., Rubel EW. Validation of the Transgenic Quail as a model for research in the Avian Nervous System – A Comparative Study of the Auditory Brainstem. J Comp Neurol. 521:5-23, 2013
Al-Roubaie S, Hughes JH, Lansford R, Lehoux S, Elizabeth A.V. Jones E Time-Lapse Microscopy of Macrophages During Embryonic Vascular Development. Dev Dyn. 241:1423-31, 2012
Aleksandrov A, Czirok A, Szabo A, Filla MB, Hossain MJ, Whelan PF, Lansford R, Rongish BJ. Convective tissue movements play a major role in avian endocardial morphogenesis. Dev Bio. 363:348-61, 2012
Bower D, Sato Y, Lansford R. Dynamic lineage analysis of embryonic morphogenesis using transgenic quail and 4D multispectral imaging. Genesis 49:619-643, 2011
Canaria C, Lansford R. 4D fluorescent imaging of embryonic quail development. CSH Protoc. doi:10.1101/pdb.top066613, 2011
Canaria C, Lansford R. Preparation and 4D fluorescent imaging of quail embryos. CSH Protoc. doi:10.1101/pdb.prot066621, 2011
Ohn J, Yang J, Fraser SE, Lansford R, Liebling M. High-speed multi-color microscopy of repeating dynamic processes. Genesis 49:514-521, 2011
Sato Y, Poynter G, Huss D, Filla MB, Rongish BJ, Little CD, Fraser SE, Lansford R. Dynamic analysis of embryonic vascular development in transgenic quail. PLoS One 5:1-12, 2010
Neural and vascular development
Single cell heterogeneity
Metabolic metabolism during development
My group investigates the fundamental principles that guide how cells self organize through collective interactions to bring about changes in embryonic form and function, with our particular focus in the developing neural and vascular systems. We are interested in how molecules work together to control the timing and the spatial pattern of cell differentiation in developing tissues and stem cell systems. Over the past decade we developed transgenic, fluorescent protein (FP) expressing Japanese quail as an experimental system. We simultaneously developed state-of-the-art live cell and tissue imaging methodologies and use them to better understand the complex cellular processes underlying embryonic development and disease. The transgenic quail model system is rapidly emerging as we share our transgenic lines prior to publication and teach labs worldwide how to work with the tools and techniques of imaging and genetically perturbing their embryos.
What is occurring in a cell at one moment in time may not be true at another moment under different natural or pathological conditions, such that methods that give a snapshot of gene expression or the cellular state might not provide a good depiction of the developmental process over time. In addition, it is simply not feasible to dynamically analyze cell behaviors and tissue movements during the equivalent of the first trimester of human development using rodent or human embryos for technical and ethical reasons. Discovering how nature assembles organs de novo within a living embryo is essential for tissue engineers to regenerate functional organs. In response to this challenge, my lab has collaborated with an interdisciplinary teams of biologists, bioengineers, physicists, mathematicians, technologists, and clinicians at Caltech, USC, and abroad for two decades to develop the Zeiss Meta and evolve multiplex 4D imaging, compose new algorithms that automate quantitative analysis, generate new multispectral fluorescent probes, create the transgenic quail model system, and devise single cell analysis techniques required to now delve deeply into the fundamental mechanisms that drive morphogenesis and organogenesis.
The form and function of embryogenesis and pathogenesis
Many diseases can be considered as a failure of development. Investigating the borderland of embryology and pathology is a fundamental method for learning the rules of development. My group investigates the fundamental principles that guide how cells self-organize through collective interactions to bring about changes in embryonic form and function. We are interested in how molecules work together to control the timing and the spatial pattern of cell differentiation in developing tissues and stem cell systems. We take an interdisciplinary approach to understand the relationships between chemical, genetic and mechanical cues that shape the developing embryo.
This image is of an embryonic day 4 Syn:H2B-EYFP transgenic quail embryo. The H2B-EYFP labels neurons in these quail lines which permit us to dynamically image neural development.
Dynamic analysis of neural and vascular development
To increase our understanding of how neural and vascular cells and their stem cell precursors are precisely patterned in space and time, we use dynamic computational imaging to study heart morphogenesis, neurovascular interactions, mid-forebrain formation and tumor angiogenesis. We are using dynamic data sets from transgenic quail to study the biomechanics of heart looping and sinoatrial node formation, along with gene expression oscillations in somitogenesis and midbrain-forebrain formation.
YFP+ endothelial cells within the developing heart region of tie1:H2B-EYFP transgenic quail embryo. We try to dynamically image developmental cell behaviors including cell division, cell death, cell growth, cell polarity, cell migration and cell shape changes. Cell shape and morphogenesis are governed by cell mechanics, which explains the forces that push, pull, bend and twist tissues into shape.
Dynamic single cell methods to study heterogeneity
To properly describe the complexity of embryogenesis we use high-resolution time-lapse imaging of quail transgenic embryos to collect data of the molecular, cellular and tissue dynamics underlying development and patterning with a previously unmatched precision. We are assembling these parameters to build a quantitative 4D-model based on biological values that combines morphogenetic and patterning aspects of embryogenesis.
YFP+ endothelial cells within the developing aortae of tie1:H2B-EYFP are localized inside of the QH1-signals demarcating every endothelial cell membrane in HH stage 11 embryos. Anterior is top.
Efficacious genome modifications in stem cells and embryos
We develop and use various gene transfer technologies in quail primordial germ cells and in human embryonic stem cells in hopes of someday genetically treating monogeneic disorders. The genetic modification could involve correction of a genetic defect in human stem cells or the mutation of a desired gene within the quail genome to model human disease. Dynamic metabolic profiling during development We are integrating imaging, genomics, proteomics and glycomics to provide powerful new tools for understanding the molecular basis of metabolism during development and disease.
Three-dimensional renderings of e10 quail developmental atlas. Unlike traditional atlases, which are based on histological sections, these atlases are built from µMRI, a nondestructive imaging modality that preserves the native morphology of tissues. Because MRI derives contrast from the paramagnetic properties of water and its chemical and physiological environment, not the optical properties of the tissues, minimal specimen preparation is necessary.
Morphogenesis is the process whereby cells reorganize in space to generate tissues, organs and organisms. Morphogenesis can ultimately be reduced to a series of changes in cell behaviors including cell shape, polarity, movement, adhesion and proliferation. Here are several diverse papers published over the past decade that highlight how we have developed optical and genetic tools and techniques that allow us to determine complete lineages for organs and to extract cell-based frameworks for use in modeling.
- Huss, D, Benazeraf B, Wallingford A, Filla M, Yang J, Fraser SE, Lansford R. Transgenic quail to dynamically image amniote embryogenesis. Development. 142:2850-59, 2015. PMID:26209648
- Huss D, Choi HM, Readhead C, Fraser SE, Pierce NA, Lansford R. Combinatorial analysis of mRNA expression patterns in mouse embryos using hybridization chain reaction. Cold Spring Harb Protoc. 2015(3):259-68, 2015. PMID: 25734068
- Sato Y, Poynter G, Huss D, Filla MB, Rongish BJ, Little CD, Fraser SE, Lansford R. Dynamic analysis of embryonic vascular development in transgenic quail. PLoS One 5:1-12, 2010. PMCID: PMC2939056
- Mahadevan A, Welsh IC, Sivakumar A, Gludish DW, Shilvock AR, Noden DM, Huss D, Lansford R, Kurpios, NA. The left-right Pitx2 pathway drives organ-specific arterial and lymphatic development in the intestine. Dev Cell. 31:1-17, 2014. PMCID: PMC4326534
- Aleksandrova A, Czirok A, Szabo A, Filla MB, Hossain MJ, Whelan PF, Lansford R, Rongish BJ. Convective tissue movements play a major role in avian endocardial morphogenesis. Dev Bio 363:348-61, 2012. PMCID: PMC3288244
- Bower D, Sato Y, Lansford R. Dynamic lineage analysis of embryonic morphogenesis using transgenic quail and 4D multispectral imaging. Genesis 49:619-643, 2011
- Canaria CC, Maloney JR, Yu CJ, Smith JO, Fraser SE, Lansford R. Formation and removal of biotinylated alkanethiolate self-assembled monolayers on gold from aqueous solutions. Lab Chip 6:289-295, 2006
- Lansford R, Bearman G, Fraser SE. Resolution of multiple GFP color variants and dyes using two-photon microscopy and imaging spectroscopy. J Biomed Optics 6:311-318, 2001
- Molecular Neuroscience: A laboratory manual. (2014) (Ed. by R Lansford) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY (ISBN: 978-1-621820-14-7)
Human Frontiers Program Grant: Quantitative analysis of somitogenesis using avian transgenic lines and real time imaging
The development and combination of quail transgenesis, new imaging protocols, biophysical approaches, quantitative analyzing techniques and 4D modeling opens up the possibility of reinvestigating axis morphogenesis and patterning processes to obtain a comprehensive understanding of their coordination.
NIH-NHLBI: Molecular anatomy of human alveolar development
The Strategic Goal of this UO1 proposal is to construct a rich multiscale atlas of human alveolar development in collaboration with other research centers, the tissue procurement center and the data management center so that LungMAP can be openly interrogated and shared with the research community.
NASA Space Act Award for Two-photon Microscope Imaging Spectrometer for Multiple Fluorescent Probes (along with Greg Bearman and Scott Fraser) 2003
R&D 100 Award for development of META multispectral imager (along with Greg Bearman, Scott Fraser, and Carl Zeiss Jena GmbH) 2002