Massachusetts Institute of Technology
Appointed in 2004
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Massachusetts Institute of Technology
Appointed in 2004
University of Kansas
Appointed in 1956
Stanford University
Appointed in 2011
Stanford University
Appointed in 1976
Harvard University Medical School
Appointed in 2014
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Harvard University Medical School
Appointed in 2014
The eukaryotic helicase CMG (Cdc45+MCM2-7+GINS) is the molecular machine that unwinds dsDNA during replication. Although CMG plays a central role in replication, key aspects of its dynamics are poorly understood. It has been proposed that before activation, loaded MCM complexes can slide on dsDNA. However, this phenomenon has not been examined under physiological conditions and its functional significance remains unclear. In addition, how the CMG helicase operates under conditions of replicative stress is not understood.
To address these questions, I will perform single-molecule imaging of MCM2-7 complexes in completely soluble Xenopus egg extracts, which were pioneered in my sponsor’s laboratory.
In Aim 1 I propose to probe the dynamics of individual dsDNA-bound MCM complexes prior to replication initiation. In particular I seek to determine whether dormant MCM complexes can slide on dsDNA in physiological conditions. In Aim 2 I propose to investigate the fate of dormant MCM complexes upon their collision with oncoming replication forks. In Aim 3 I propose to study the dynamics of the helicase after its uncoupling from the replicative polymerase, and seek to determine how the helicase activity is regulated by the activation of the DNA damage checkpoint.
Stanford University
Appointed in 1995
Oregon Health and Science University, Portland
Appointed in 2015
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Oregon Health and Science University, Portland
Appointed in 2015
University of California, Berkeley
Appointed in 1964
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University of California, Berkeley
Appointed in 1964
Whitehead Institute for Biomedical Research
Appointed in 1986
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Whitehead Institute for Biomedical Research
Appointed in 1986
Stanford University
Appointed in 1984
Boston Children's Hospital
Appointed in 2001
University of Utah School of Medicine
Appointed in 2014
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University of Utah School of Medicine
Appointed in 2014
My current research is focused on the biology and evolution of transposons, which are DNA parasites that constitute over half of the human genome. Specifically,  I am investigating the long-standing hypothesis that transposon activity is a major mechanism underlying the evolution of gene regulatory networks.
I became interested in evolutionary biology as an undergraduate at UC San Diego, where I worked with Hopi Hoekstra studying the volatile history of rodent placental proteins. I continued studying placental evolution as a graduate student at Stanford University with Julie Baker, where we found that transposons may contribute to pregnancy-related adaptations by functioning as species-specific regulatory elements.  Inspired by the potential for transposons to drive rapid evolutionary change, I decided to do my postdoc in the laboratories of Cedric Feschotte and Nels Elde at the University of Utah, where I am studying the role of transposons in shaping the evolution of human innate immune responses. Outside the lab, I enjoy the vast outdoor recreational activities in Utah, including hiking, skiing, and canyoneering.
University of Wisconsin, Madison
Appointed in 1989
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University of Wisconsin, Madison
Appointed in 1989
University of California, Los Angeles
Appointed in 1997
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University of California, Los Angeles
Appointed in 1997
Stanford University
Appointed in 2008
Current research: I study the neural circuitry and computations involved in fruit fly vision.
I initially became interested in neuroscience by looking at gross brain anatomy and how microscopic computational requirements might influence the relative sizes of different brain regions. From there, I moved on to studying worms, an organism whose entire neural network is known, and examined how this small nervous system could sense and respond to environmental cues to navigate its environment. I now work on visual circuitry and computations in the fruit fly, an ideal model system for its genetics and behavior, and an ideal system to model. When I’m not in the lab, I like to get out hiking or biking, and in general enjoying the California sun.
University of California, Berkeley
Appointed in 2007
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University of California, Berkeley
Appointed in 2007
Stanford University
Appointed in 1983
University of California, San Francisco
Appointed in 1984
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University of California, San Francisco
Appointed in 1984
University of Switzerland, Zurich
Appointed in 1972
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University of Switzerland, Zurich
Appointed in 1972
Washington University in St. Louis
Appointed in 2012
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Washington University in St. Louis
Appointed in 2012
University of California, San Francisco
Appointed in 2006
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University of California, San Francisco
Appointed in 2006
Fred Hutchinson Cancer Center
Appointed in 1999
Harvard University
Appointed in 1971
University of California, San Diego
Appointed in 1971
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University of California, San Diego
Appointed in 1971
University of Massachusetts Medical School /
Yale University
Appointed in 2008
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University of Massachusetts Medical School / Yale University
Appointed in 2008
My research involves the engineering of protein binding modules from Tetratricopeptide repeats using both selection from randomized libraries and rational design. Our goal is to design low cost medical diagnostics, for example, a CD4 test practical for the management of HIV+ patients in the developing world. Early in my freshman year of college, I began my career in science working in laboratories, taking on projects ranging from the enzymatic bleaching of paper to the studies of pathogenic nematodes and complex carbohydrates. In graduate school at Emory University, mentored by Xiaodong Cheng, I focused on the structural biology of the “histone code.¬î At Yale, in the lab of Lynne Regan, I have turned to an engineering approach, using rational structure-based design and library selection to develop new, inexpensive diagnostics, and also to investigate fundamental questions of protein-ligand interaction. Long-term goals involve development of model systems to probe the molecular/structural evolution of novel interactions and their enhanced affinity and selectivity in directed evolution experiments.
University of California, Berkeley
Appointed in 2020
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University of California, Berkeley
Appointed in 2020
CRISPR-Cas systems provide prokaryotes with an adaptive immune mechanism whereby foreign nucleic acids are recorded and, when re-encountered, destroyed. Foreign DNA fragments are incorporated into the host’s CRISPR array and later transcribed and processed into crRNAs. crRNAs then assemble with Cas effector proteins and guide them to complementary nucleic acid sequences for destruction. The well-known Cas9 cleaves DNA site-specifically, and thus has been widely adopted as a programmable tool for gene editing. Analogous tools for cleaving RNA are lacking, with the exception of Cas13 which exhibits non-site-specific cleavage and toxic off-target effects. My research aims to discover and characterize new Cas effectors for precise RNA-cleavage in prokaryotes, and further develop them into tools for detection and cleavage of RNA sequences in eukaryotes.
Pennsylvania State University
Appointed in 1980
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Pennsylvania State University
Appointed in 1980
Massachusetts Institute of Technology /
Whitehead Institute
Appointed in 1982
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Massachusetts Institute of Technology / Whitehead Institute
Appointed in 1982
Massachusetts Institute of Technology
Appointed in 1994
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Massachusetts Institute of Technology
Appointed in 1994
Whitehead Institute for Biomedical Research
Appointed in 2018
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Whitehead Institute for Biomedical Research
Appointed in 2018
One of the special features of animal and plant cells is their differentiation into hundreds of specialized types. How these diverse cells originated is a fundamental question in evolution. To approach this question, I am using single-cell RNA sequencing to characterize hundreds of cell types across diverse species of planarians and their distant relatives. This will enable a search for key regulatory factors in an unprecedented range of differentiation pathways, guided by the fact that conserved expression is a common feature of such genes. Planarians are particularly well-suited for testing the function of fate-specifying genes because cell differentiation is an ongoing process in all tissues in the adult stage, and during regeneration. Through this approach, I propose to learn general principles concerning the molecular basis of cell type homology across diverse animal taxa._x000D_
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University of Wisconsin, Madison
Appointed in 1973
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University of Wisconsin, Madison
Appointed in 1973
Whitehead Institute for Biomedical Research
Appointed in 1984
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Whitehead Institute for Biomedical Research
Appointed in 1984
University of Washington
Appointed in 2007
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University of Washington
Appointed in 2007
Stanford University
Appointed in 2006
University of Washington
Appointed in 2008
Baylor College of Medicine
Appointed in 1998
Cornell University
Appointed in 1983
Sidney Farber Cancer Institute
Appointed in 1979
University of California, Berkeley
Appointed in 2013
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University of California, Berkeley
Appointed in 2013
Nitric oxide (NO) is a ubiquitous gasotransmitter involved in vasorelaxation, neurodegeneration, apoptosis, and other processes, and linked to numerous pathologies, including cancer. A major mechanism of NO signaling is S-nitrosation, the oxidative modification of cysteine residues, but how this occurs in vivo is poorly understood. Copper ions catalyze Snitrosation in vitro, while recent data point to mobile pools of copper playing unknown roles in signaling pathways. This proposal aims to connect copper- and NO-mediated signaling, using the lipolysis pathway of adipocytes as a model system. Our preliminary data suggest copper and NO modulate the activity of phosphodiesterase (PDE) 3B. We propose that copper, bound to a protein or small molecule, catalyzes S-nitrosation of PDE3B, inhibiting the enzyme. We will test this hypothesis by altering cellular copper and NO levels via gene knockdowns, and assaying PDE3B activity in extracts. We will detect differences in PDE3B S-nitrosation under these conditions and determine the cysteine(s) modified. Finally, we will search for endogenous copper ligands and reconstitute the S-nitrosation system in vitro. These studies will yield insights into NO’s physiology, unravel a novel signaling role of copper, and motivate examination of copper signaling in other mammalian cell types.
Stanford University
Appointed in 1994
University of Colorado, Boulder
Appointed in 1981
Albert Einstein College of Medicine
Appointed in 1997
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Albert Einstein College of Medicine
Appointed in 1997
University of California, San Francisco
Appointed in 2000
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University of California, San Francisco
Appointed in 2000
Peter Bent Brigham Hospital
Appointed in 1956
Johns Hopkins University
Appointed in 1973
Boston Children's Hospital
Appointed in 1996
University of California, Los Angeles
Appointed in 1970
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University of California, Los Angeles
Appointed in 1970
Yale University
Appointed in 2021
A single neuron can use more than one neurotransmitter to signal with neighboring cells and regulate, for example, movement, reward and vision in mammalian systems. These dual-transmitter neurons can segregate molecularly distinct presynaptic terminals within a single axon and each neurotransmitter can regulate an independent or complementary role within a functional circuit. Although dual-transmitter neurons are conserved in vertebrates and invertebrates, very little is known about what differentially regulates neurotransmitter-specific synaptic pools and how this intracellular specificity shapes circuit function. Here, I propose to establish in vivo models of dual-transmitter neurons and use the well-mapped nervous system of the nematode Caenorhabditis elegans to understand how molecularly distinct synapses organize and segregate within a single neuron to regulate animal behavior. I will focus on the motor neuron SMD, the interneuron RIB and the neurosecretory NSM neuron to establish in vivo paradigms of dual-transmission with trackable behavioral consequences. My goal is to carry out a genetic screen to identify genes that organize neurotransmitter-specific synapses and track the functional consequences of ablating one subset of synapses. This proposal could reveal conserved cell biological programs of intracellular synapse placement in dual-transmitter neurons and link them with circuit function in a living organism.
Cornell University
Appointed in 1975
University of North Carolina, Chapel Hill
Appointed in 1978
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University of North Carolina, Chapel Hill
Appointed in 1978
Stanford University
Appointed in 1990