Directory - Jane Coffin Childs Memorial Fund

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Iain M. Cheeseman, Ph.D. Jane Coffin Childs Fellow - Ludwig Institute

University of California, San Diego

Project Title: Dissecting kinetochore function in C Elegans

Alice E. Chen, Ph.D. Jane Coffin Childs - Merck Fellow

Harvard University

Project Title: Directed differentiation of ES cells into beta-cells

Jichao H.. Chen, Ph.D. Jane Coffin Childs Fellow

Stanford University

Project Title: Mechanism of airway tube size control during lung development

Yen-Chih J. Chen, Ph.D. Jane Coffin Childs Fellow

Scripps Research Institute

Project Title: Catalytic antibodies

Xi Chen, Ph.D. Jane Coffin Childs Fellow

Harvard Medical School

Project Title: RNA circuits for cancer theranostics

Jia-Yun H.. Chen, Ph.D. Jane Coffin Childs Fellow

Harvard Medical School

Project Title: Molecular dynamics of oncogene-induced senescence

Yi Chen, Ph.D. Jane Coffin Childs Fellow

Dana-Farber Cancer Institute

Project Title: The role of Kcnk3 and membrane potential in adipose tissue thermogenesis

My current research focuses on the molecular mechanisms underlying adipose tissue development and metabolism. In particular, I use genetic and biochemical approaches to identify the molecular differences between the energy-storing white fat and energy-dissipating brown/beige fat in the hope of using those differences to help design therapeutic strategies for the prevention and treatment of obesity._x000D_
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Brown and beige fat dissipates energy as heat in a process known as non-shivering thermogenesis. The transcriptional regulator Prdm16 was previously identified to facilitate thermogenesis; however, its relevant target genes remain incompletely known. Through ChIP-Seq and RNA-Seq, we have identified a number of potential Prdm16 targets. Among those, I focus on delineating the functions of a rectifying potassium channel Kcnk3 in thermogenesis. Kcnk3 is known to set the plasma membrane potential by generating potassium currents in neurons. I hypothesize that Kcnk3 sets the appropriate membrane potential in thermogenic adipocytes, which may be important for thermogenesis. I will test this hypothesis using fat-specific Kcnk3 knockout mice.

Feng Chen, Ph.D. Jane Coffin Childs Fellow

University of California, San Francisco

Project Title: Understanding liver bile duct formation to grow biliary tubes in vitro

Yu-Chan Chen, Ph.D. Jane Coffin Childs Fellow

Stanford University

Project Title: Dissecting the protein folding mechanism by the TRiC chaperonin

Proteostasis is a central mechanism to regulate the health of the cellular proteome. Proteostasis dysfunction has been directly implicated in age-related diseases, including cancer. A central but very poorly understood component of proteostasis network is the eukaryotic chaperonin, TRiC/CCT. TRiC is an essential chaperone that assists folding and assembly of many proteins fundamentally important to cancer, including the tumor suppressors p53, VHL, telomerase as well as other cell cycle regulators. It is, therefore, not surprising that mis-regulation of TRiC is also linked to numerous pathological conditions. Indeed, several TRiC subunits are highly up-regulated in cancer, and their up-regulation is linked to poor prognosis. The paucity of structural and mechanistic knowledge on this complex has hindered the development of therapeutic strategies targeting TRiC. Therefore, my research in the Frydman lab focuses on closing this gap by defining the molecular basis of human TRiC to fold the key disease-linked proteins. I am interested in combining biochemical and structural methods to elucidate the underlying principles by which TRiC recognizes and folds proteins. I anticipate the result of this work will provide mechanistic insights relevant to human diseases.

Jin H.. Chen, Ph.D. Jane Coffin Childs - HHMI Fellow

University of California, San Francisco

Project Title: Systemic analysis of the relationship between incRNAs and translation

Long non-coding RNAs (lncRNAs) have recently emerged as key functional molecules in gene regulation, with increasing evidence pointing to a role for lncRNAs in human diseases such as cancer. While the importance of a subset of nuclear lncRNAs in epigenetic and transcriptional gene regulation is well established, lncRNAs are also found in the cytoplasm and may function in different cytoplasmic processes including translational control. In particular, lncRNAs may regulate the translation of other transcripts; or, they may be associated with ribosomes and translated to produce short regulatory “micropeptides”. However, studying the roles for lncRNAs in translation has been hindered by the lack of high-throughput methods to systematically identify lncRNA candidates and probe how lncRNAs act globally to impact translation. Here, I propose a research program that uses a repertoire of genome-wide techniques, combining CRISPR interference and ribosome profiling, to provide fundamental insights into the novel role of lncRNAs in translational control.

Ji H. Chen, Ph.D. Jane Coffin Childs Fellow

Public Health Research Institute of the City of New York

Project Title: Viral carcinogenesis

Reproductive aging is a global challenge. Older men and women face fertility loss and a higher chance of having children with genetic disorders. Currently, we lack a detailed molecular understanding of what causes reproductive aging in vertebrates. I am developing an emerging short-lived model system, the African killifish, to study¬†vertebrate reproductive aging. The lifespan of this organism¬†is 4 times shorter than mice and 7 times shorter than zebrafish. I will combine my graduate training (gamete biology) with the expertise of the Brunet Lab (killifish and aging) to probe the molecular basis of age-dependent fertility decline in the killifish and identify potential targets for therapeutic intervention. These studies will shed light on methods¬†to protect or rejuvenate the germline from aging, which can have a profound impact on human fertility.

James Chen, Ph.D. Jane Coffin Childs Fellow

New York University

Project Title: Structure of a virulence-associated membrane transporter in

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.

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

University of California, San Diego

Project Title: In situ structure of WT and PD mutant LRRK2 on cellular membranes

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.

Jingyi H.. Chen, Ph.D. Jane Coffin Childs Fellow

University of Washington

Project Title: Evaluating neuromodulatory networks across brain states

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 LC^DBH 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 LC^DBH 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.

Shepley Sc. Chen, Ph.D. Jane Coffin Childs Fellow

Michigan State University

Project Title: Action of gibberellin on germination enzymes

Ji H. H.. Chen, Ph.D. Jane Coffin Childs Fellow

Rockefeller University

Project Title: Viral carcinogenesis

Ruoyu Chen, Ph.D. Jane Coffin Childs Fellow

Harvard University

Project Title: Neural and molecular mechanism of social drive

Biology often reuses the same basic “building blocks” for similar functions. Dr. Ruoyu Chen studied RNA–protein clusters (called RNP granules) in fruit fly reproductive cells and made a surprising discovery that changed how scientists think these granules work. Because similar granules also play important roles in neuronal functions, Chen became interested in neuroscience and now wants to study the cellular and molecular underpinnings of the drive for social interaction.

As a graduate student in Ruth Lehmann’s lab at the Whitehead Institute for Biomedical Research, Chen studied RNP granules, which are small cell compartments made of RNA and RNA-binding proteins. Scientists had long thought these granules turn off protein production from the RNAs inside them. Chen found the opposite in fly germ cells: the RNAs in these granules are actively being used to make proteins. This was a paradigm-shifting finding for the field and led Chen to consider other areas of biology where this kind of translational regulation is important.

Since similar RNA granules help move RNAs around long nerve cells and make proteins in specific places, Chen began focusing on how these processes affect brain function and behavior. As a Jane Coffin Childs Fellow in Catherine Dulac’s lab at Harvard, he will study the brain circuits and molecular signals that control the desire for social interaction. He will use social isolation to probe these systems, with the hope of understanding why loneliness is linked to poor health and some mental health disorders.

Selina Chen-Kiang, Ph.D. Jane Coffin Childs Fellow

Rockefeller University

Project Title: Turnover mRNA

Peter T. Cherbas, Ph.D. Jane Coffin Childs Fellow

University of Cambridge, England /
Harvard University

Project Title: Ecdysone action in Drosophila

Cheng-Ting Chien, Ph.D. Jane Coffin Childs Fellow

University of California, San Francisco

Project Title: Atonal in the development of Drosophila PNS

Peter Chien, Ph.D. Jane Coffin Childs Fellow

Massachusetts Institute of Technology

Project Title: Conservation of AAA:+ protease substrates

Masahiro Chiga, M.D. Jane Coffin Childs Fellow

University of Kansas

Project Title: Transplantation of mouse tumors

William S. Childers, Ph.D. Jane Coffin Childs Fellow

Stanford University

Project Title: Exploring the role of kinase subcellular localization in bacterial cell cycle regulation

Geoffrey J. Childs, Ph.D. Jane Coffin Childs Fellow

Stanford University

Project Title: Messenger RNAs transcription and processing of histones

Gheorghe Chistol, Ph.D. Jane Coffin Childs Fellow

Harvard Medical School

Project Title: Probing the dynamics of the eukaryotic replicative helicase

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¬ís 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.

Sung Kay Chiu, Ph.D. Jane Coffin Childs Fellow

Stanford University

Project Title: Identification of an inducer of tracheal branching

Ryan Chow, M.D., Ph.D. JJJ Charitable Foundation- Jane Coffin Childs Fellow

University of Pennsylvania

Project Title: De novo design of peptides to perturb oncogenic transcriptional condensates

As a hematology and oncology fellow, Ryan Chow, M.D., Ph.D., is often faced with the limitations of our current cancer therapies. His goal as a JJJ Charitable Foundation- Jane Coffin Childs Fellow is to build on his graduate work of identifying genetic insults to develop a new class of anti-cancer therapies that function by disarming oncogenic transcription factors.

In Sidi Chen’s lab at Yale University, Chow created new CRISPR screening methods to study which genes drive cancer. It should be noted that Chow’s overwhelming research production as a graduate student cannot be completely covered in this space, but we’ll look at a few examples. For example, he used AAV viruses to deliver CRISPR tools into animals and find tumor-suppressor genes in glioblastoma and liver cancer. Then, Chow adapted his CRISPR screens to enable stepwise mutation of multiple genes which can capture the sequential nature of mutations, for instance in non-small cell lung cancer. While Chow’s findings emphasize the power of CRISPR screens in revealing novel cancer genetics, he quickly realized the impracticality of this modality for cancer therapies.

Now in Pranam Chatterjee’s and Katalin Susztak’s labs at the University of Pennsylvania, Chow is taking a different approach: designing brand-new peptides to target cancer-driving transcription factors. These proteins are important targets but have been hard to drug with traditional medicines because they are flexible and located in the cell nucleus. Chow plans to use deep learning to design peptides that bind these transcription factors and test whether they can rewrite cancer gene programs and eliminate tumors.

Sandipan Chowdhury, Ph.D. Jane Coffin Childs - Merck Fellow

Oregon Health and Science University

Project Title: Structure of the NR1-NR2A subtype of the NMDA receptor in the open state

Michel Chretien, M.D. Jane Coffin Childs Fellow

University of California, Berkeley

Project Title: Polypeptide and protein chemistry

Michael F. Christman, Ph.D. Jane Coffin Childs Fellow

Whitehead Institute

Project Title: Molecular-genetic study of enhancers in yeast

Gilbert Chu, M.D., Ph.D. Jane Coffin Childs Fellow

Stanford University

Project Title: Can yeast genes rescue Xeroderma pigmentosum cells

Katrin F . Chua, Ph.D. Jane Coffin Childs Fellow

Children's Hospital of Boston

Project Title: Mechanism and machinery of class switch recombination

Edward B. Chuong, Ph.D. Jane Coffin Childs - HHMI Fellow

University of Utah School of Medicine

Project Title: Co-option of endogenous retroviruses for host immune responses

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.

Diane L. Church, Ph.D. Jane Coffin Childs Fellow

University of Wisconsin, Madison

Project Title: Trans-splicing in C. elegans

Thomas R. Clandinin, Ph.D. Jane Coffin Childs Fellow

University of California, Los Angeles

Project Title: Analysis of connectivity in the Drosophila eye

Damon A. Clark, Ph.D. Jane Coffin Childs Fellow

Stanford University

Project Title: Visual feedback modulation in behaving Drosophila

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¬ím not in the lab, I like to get out hiking or biking, and in general enjoying the California sun.

Anne-Kathrin Classen, Ph.D. Jane Coffin Childs Fellow

University of California, Berkeley

Project Title: The polycomb family of epigenetic transcriptional repressors and their role in Drosophila growth control

Michael L. Cleary, M.D. Jane Coffin Childs Fellow

Stanford University

Project Title: Diagnosis of lymphoma based on lg gene rearrangements

Dennis O. Clegg, Ph.D. Jane Coffin Childs Fellow

University of California, San Francisco

Project Title: Neuronal development

John M. Coffin, Ph.D. Jane Coffin Childs Fellow

University of Switzerland

Project Title: RNA tumor-virus infection

Thomas Cohen, Ph.D. Jane Coffin Childs Fellow

Washington University in St. Louis

Project Title: Protein sequencing through single molecule detection

Antonio Colavita, Ph.D. Jane Coffin Childs Fellow

University of California, San Francisco

Project Title: Analysis of semaphoring in C. elegans and vertebrates

David W. Colby, Ph.D. Jane Coffin Childs Fellow

University of California, San Francisco

Project Title: Structural basis of synthetic prion infectivity

Hilary Coller, Ph.D. Jane Coffin Childs Fellow

Fred Hutchinson Cancer Center

Project Title: Cell cycle with the use of transcriptional arrays

Robert E. Collins, Ph.D. Jane Coffin Childs Fellow

University of Massachusetts Chan Medical School and Yale /
Yale University

Project Title: RabGDI displacement factors: mechanism and function in membrane traffic

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.

Kim D. Collins, Ph.D. Jane Coffin Childs Fellow

Harvard University

Project Title: Enzymatic catalysis

John Collins, Ph.D. Jane Coffin Childs Fellow

University of California, San Diego

Project Title: Bacterial episomal DNA

David Colognori, Ph.D. Jane Coffin Childs Fellow

University of California, Berkeley

Project Title: Developing new CRISPR-Cas system for eukaryotic RNA knockdown and detection

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‚Äôs 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.

Giovanna Colombo, Ph.D. Jane Coffin Childs Fellow

Pennsylvania State University

Project Title: Inactivation of dopamine - beta hydroxylase

Sally J. Compere, Ph.D. Jane Coffin Childs Fellow

Massachusetts Institute of Technology /
Whitehead Institute

Project Title: Molecular characterization of oncogenes

Barbara Conradt, Ph.D. Jane Coffin Childs Fellow

Massachusetts Institute of Technology

Project Title: Cell death of the linker cell in C. elegans