Directory

Image of Selina Chen-Kiang
Selina Chen-Kiang Jane Coffin Childs Fellow

Rockefeller University

Appointed in 1978

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Image of James Chen, Ph.D.
James Chen, Ph.D. Jane Coffin Childs Fellow

New York University, Grossman School of Medicine

Appointed in 2021

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Mycobacterium tuberculosis, the causative agent of tuberculosis, is one of the leading causes of death due to infectious disease. Mtb establishes a replicative niche within the phagosomal compartment of host macrophages where it siphons nutrients from the host cell for its survival. To thrive within this hostile environment, Mtb has evolved a complex, protective cell envelope along with an ensemble of active transporters to import nutrients across this nearly impermeable barrier. The Mammalian Cell Entry (MCE) proteins have been implicated in nutrient transport as well as outer membrane maintenance and are important virulence factors in Mtb.  However, the molecular bases for these functions are not known and the MCE proteins could play additional roles in the cell that have yet to be characterized. Therefore, I am currently determining the first structures of the mycobacterial MCE proteins and their associated factors using a combination of endogenous purification strategies and cryo-electron microscopy (cryo-EM), and developing in vivo assays to monitor MCE substrate binding and transport. This work will provide structural and mechanistic insights into these important virulence factors, which are potential targets for drug development.

 

Image of Siyu Chen, Ph.D.
Siyu Chen, Ph.D. Jane Coffin Childs - HHMI Fellow

University of California, San Diego

Appointed in 2023

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Mutations in LRRK2, a multi-domain kinase and GTPase, is the most frequent cause of familial Parkinson’s disease. However, we currently lack the detailed understanding of LRRK2 function that could lead to therapeutics for Parkinson’s. Dr. Siyu Chen will use cryo-EM and cryo-ET to study LRRK2 and its mutants in biochemical reconstitutions and in cells. Dr. Chen will conduct these experiments in Dr. Elizabeth Villa’s lab at the University of California, San Diego. These experiments will directly visualize the molecular mechanisms of LRRK2 and interacting partners’ function in the cell, and how pathogenic mutations disrupt these processes. Therefore, Dr. Chen’s research may inform on novel therapies for Parkinson’s disease.

As a graduate student in Dr. Yuan He’s lab at Northwestern University, Chen studied DNA double-strand break repair. Specifically, Dr. Chen used Cryo-EM to solve two key intermediate states in the non-homologous end-joining pathway (NHEJ). These structures revealed novel interaction surfaces between NHEJ proteins and allowed Dr. Chen to propose a near complete reaction cycle for NHEJ. Dr. Chen will now apply his cryo-EM expertise to LRRK2 and will use cryo-ET to visualize LRRK2 in cells.

Image of Jingyi Chen, Ph.D.
Jingyi Chen, Ph.D. Jane Coffin Childs Fellow

University of Washington

Appointed in 2022

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Internal brain states greatly influence our sensations and perception of the external world. Incidents such as stress, hunger, thirst, and pregnancy have all been described as inducing different ‘brain states’ within individuals, altering basic neural properties such as sensory perception, memory, interception, and attention. However, we do not understand how our brains dynamically shape our perceptions and behaviors during state shifts. Here we aimed to create stable brain state models by exposing animals to either chronic social isolation or exercise, two opposing types of behavioral intervention to represent positive and negative experiences. By measuring multi-domain behavioral profiles across the brain during long-term social isolation or exercise, we tested if these biological fingerprints can predict animals’ brain states. To further dissect the neuromodulation changes during brain state shifts, we focused first on the locus coeruleus (LC). LC both receives and sends broad projections throughout the brain. LC cells could then mediate brain-wide changes through its noradrenergic population to control arousal, attention, and sensory perceptions. When simultaneously imaging LCDBH cell body and terminal activities across multiple brain regions, we observed different activity patterns when mice were presented with a diverse array of stimuli. We have also observed dynamic single-cell activities toward different sensory cues, which further confirms the heterogeneity within the LCDBH population. By combing in vivo imaging, circuitry mapping, and biochemical detection, we aim to examine the neuromodulatory signaling dynamics in and out of LC during brain state shifts induced by long-term exercise and social isolation.

 

Image of Peter T. Cherbas
Peter T. Cherbas Jane Coffin Childs Fellow

University of Cambridge, England /
Harvard University

Appointed in 1973

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Image of Cheng-Ting Chien
Cheng-Ting Chien Jane Coffin Childs Fellow

University of California, San Francisco

Appointed in 1994

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Image of Peter Chien
Peter Chien Jane Coffin Childs Fellow

Massachusetts Institute of Technology

Appointed in 2004

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Image of Masahiro Chiga
Masahiro Chiga Jane Coffin Childs Fellow

University of Kansas

Appointed in 1956

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Image of W. Seth Childers
W. Seth Childers Jane Coffin Childs Fellow

Stanford University

Appointed in 2011

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Image of Geoffrey J. Childs
Geoffrey J. Childs Jane Coffin Childs Fellow

Stanford University

Appointed in 1976

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Image of Gheorghe Chistol
Gheorghe Chistol Jane Coffin Childs Fellow

Harvard University Medical School

Appointed in 2014

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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.

Image of Sung Kay Chiu
Sung Kay Chiu Jane Coffin Childs Fellow

Stanford University

Appointed in 1995

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Image of Sandipan Chowdhury
Sandipan Chowdhury Jane Coffin Childs - Merck Fellow

Oregon Health and Science University, Portland

Appointed in 2015

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Image of Michel Chretien
Michel Chretien Jane Coffin Childs Fellow

University of California, Berkeley

Appointed in 1964

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Image of Michael F. Christman
Michael F. Christman Jane Coffin Childs Fellow

Whitehead Institute for Biomedical Research

Appointed in 1986

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Image of Gilbert Chu
Gilbert Chu Jane Coffin Childs Fellow

Stanford University

Appointed in 1984

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Image of Katrin Chua
Katrin Chua Jane Coffin Childs Fellow

Boston Children's Hospital

Appointed in 2001

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Image of Edward Chuong
Edward Chuong Jane Coffin Childs - HHMI Fellow

University of Utah School of Medicine

Appointed in 2014

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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.

Image of Diane L. Church
Diane L. Church Jane Coffin Childs Fellow

University of Wisconsin, Madison

Appointed in 1989

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Image of Thomas R. Clandinin
Thomas R. Clandinin Jane Coffin Childs Fellow

University of California, Los Angeles

Appointed in 1997

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Image of Damon A. Clark
Damon A. Clark Jane Coffin Childs Fellow

Stanford University

Appointed in 2008

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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.

Image of Anne-Kathrin Classen
Anne-Kathrin Classen Jane Coffin Childs Fellow

University of California, Berkeley

Appointed in 2007

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Image of Michael L. Cleary
Michael L. Cleary Jane Coffin Childs Fellow

Stanford University

Appointed in 1983

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Image of Dennis O. Clegg
Dennis O. Clegg Jane Coffin Childs Fellow

University of California, San Francisco

Appointed in 1984

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Image of John M. Coffin
John M. Coffin Jane Coffin Childs Fellow

University of Switzerland, Zurich

Appointed in 1972

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Image of Thomas Cohen
Thomas Cohen Jane Coffin Childs Fellow

Washington University in St. Louis

Appointed in 2012

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Image of Antonio Colavita
Antonio Colavita Jane Coffin Childs Fellow

University of California, San Francisco

Appointed in 1996

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Image of David W. Colby
David W. Colby Jane Coffin Childs Fellow

University of California, San Francisco

Appointed in 2006

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Image of Hilary Coller
Hilary Coller Jane Coffin Childs Fellow

Fred Hutchinson Cancer Center

Appointed in 1999

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Image of Kim D. Collins
Kim D. Collins Jane Coffin Childs Fellow

Harvard University

Appointed in 1971

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Image of John Collins
John Collins Jane Coffin Childs Fellow

University of California, San Diego

Appointed in 1971

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Image of Robert E. Collins
Robert E. Collins Jane Coffin Childs Fellow

University of Massachusetts Medical School /
Yale University

Appointed in 2008

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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.

Image of David Colognori
David Colognori Jane Coffin Childs Fellow

University of California, Berkeley

Appointed in 2020

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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.

Image of Giovanna Colombo
Giovanna Colombo Jane Coffin Childs Fellow

Pennsylvania State University

Appointed in 1980

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Image of Sally J. Compere
Sally J. Compere Jane Coffin Childs Fellow

Massachusetts Institute of Technology /
Whitehead Institute

Appointed in 1982

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Image of Barbara Conradt
Barbara Conradt Jane Coffin Childs Fellow

Massachusetts Institute of Technology

Appointed in 1994

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Image of Thomas Cooke
Thomas Cooke Jane Coffin Childs - HHMI Fellow

Whitehead Institute for Biomedical Research

Appointed in 2018

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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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Image of Geoffrey M. Cooper
Geoffrey M. Cooper Jane Coffin Childs Fellow

University of Wisconsin, Madison

Appointed in 1973

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Image of Douglas N.W. Cooper
Douglas N.W. Cooper Jane Coffin Childs Fellow

Whitehead Institute for Biomedical Research

Appointed in 1984

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Image of Gregory M. Cooper
Gregory M. Cooper Jane Coffin Childs - Merck Fellow

University of Washington

Appointed in 2007

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Image of Gregory A. Cope
Gregory A. Cope Jane Coffin Childs Fellow

Stanford University

Appointed in 2006

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Image of Jacob Corn
Jacob Corn Jane Coffin Childs Fellow

University of Washington

Appointed in 2008

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Image of David K. Cortez
David K. Cortez Jane Coffin Childs Fellow

Baylor College of Medicine

Appointed in 1998

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Image of Maria C. Costanzo
Maria C. Costanzo Jane Coffin Childs Fellow

Cornell University

Appointed in 1983

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Image of Thomas Cotner
Thomas Cotner Jane Coffin Childs Fellow

Sidney Farber Cancer Institute

Appointed in 1979

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Image of Joseph Cotruvo
Joseph Cotruvo Jane Coffin Childs Fellow

University of California, Berkeley

Appointed in 2013

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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.

Image of Peter A. Covitz
Peter A. Covitz Jane Coffin Childs Fellow

Stanford University

Appointed in 1994

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Image of George N. Cox
George N. Cox Jane Coffin Childs Fellow

University of Colorado, Boulder

Appointed in 1981

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Image of Jeffrrey S. Cox
Jeffrrey S. Cox Jane Coffin Childs Fellow

Albert Einstein College of Medicine

Appointed in 1997

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Image of Daniel N. Cox
Daniel N. Cox Jane Coffin Childs Fellow

University of California, San Francisco

Appointed in 2000

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Image of Jean Crabbe
Jean Crabbe Jane Coffin Childs Fellow

Peter Bent Brigham Hospital

Appointed in 1956

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