Directory - Jane Coffin Childs Memorial Fund

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Debra K. Wiest, Ph.D. Jane Coffin Childs Fellow

California Institute of Technology

Project Title: snRNP interactions of the yeast splicing protein PRP4

Peter Wigley, Ph.D. Jane Coffin Childs Fellow

University of Wisconsin, Madison

Project Title: Post-transcriptional control of gene expression

Russell G. Wilkinson, Ph.D. Jane Coffin Childs Fellow

Johns Hopkins University

Project Title: Structure and composition of core portion of the cell wall lipopolysaccharide of E. coli

James R. Williamson, Ph.D. Jane Coffin Childs Fellow

University of Colorado, Boulder

Project Title: Preparing active subsystems of Tetrahymena ribozyme

David B. Wilson, Ph.D. Jane Coffin Childs Fellow

Johns Hopkins University

Project Title: Protein chemistry

Charles Wilson, Ph.D. Jane Coffin Childs Fellow

Harvard Medical School

Project Title: Characterization of randomly-selected functional RNAs

Joan E. Wilson, Ph.D. Jane Coffin Childs Fellow

Stanford University

Project Title: Identification of picornavirus-susceptibility genes

Jeffrey L. Winkelhake, Ph.D. Jane Coffin Childs Fellow

Salk Institute for Biological Studies

Project Title: Mechanism of tumor metastasis

Mathew M. Winkler, Ph.D. Jane Coffin Childs Fellow

University of Hawaii and University of California, Davis /
University of California, Davis

Project Title: Translational regulation of protein synthesis

Astar Winoto, Ph.D. Jane Coffin Childs Fellow

Whitehead Institute

Project Title: Immunoglobulin DNA rearrangement enzyme(s)

Jay A. Winsten, Ph.D. Jane Coffin Childs Fellow

Harvard Medical School

Project Title: Chain termination in eukaryotes

Charles G. Winter, Ph.D. Jane Coffin Childs Fellow

Johns Hopkins University

Project Title: Properties of mitochondrial membranes

Edward A. Wintner, Ph.D. Jane Coffin Childs Fellow

Harvard University

Project Title: Combinatorial design of a PH-domain binder

Krista L. Witte, Ph.D. Jane Coffin Childs Fellow

University of California, Berkeley

Project Title: The generation of new tRNAs to expand the genetic code

Image of Eilika U. Woehl Weber-Ban, Ph.D.

Eilika U. Woehl Weber-Ban, Ph.D. Jane Coffin Childs Fellow

Yale University

Project Title: Role of the chaperone component of C1pAP protease

Nancy D. Wolfson, Ph.D. Jane Coffin Childs Fellow

University of Brussels

Project Title: Physiology and histochemistry of developing amphibian eggs and embryos

Eve J. Wolinsky, M.D., Ph.D. Jane Coffin Childs Fellow

Massachusetts Institute of Technology /
Columbia University

Project Title: Egg-laying constitutive mutants of the nematode C elegans

Christina M . Woo, Ph.D. Jane Coffin Childs - HHMI Fellow

University of California, Berkeley

Project Title: Development of an isotopic labeling approach for rapid profiling of the O-glycoproteome

My research involves using isotopic labeling strategies and computational methods to enable a novel chemical glycoproteomics platform termed Isotope Targeted Glycoproteomics (IsoTaG). ¬†Given the strong correlation of altered glycosylation patterns with malignancy, glycosylated proteins may be an information-rich subset of the proteome from which cancer biomarkers can be discovered. We employ metabolic labeling as a means to tag specific classes of glycoproteins for enrichment from human tissue samples and subsequent identification by mass spectrometry. A challenge in this endeavor is defining sites of glycosylation on peptide digests derived from such complex samples. To facilitate this effort, we invented a targeted strategy to enable the detection and identification of glycosylated peptides independent of the mass of the pendant glycan. Collectively, these tools allow us to quantitatively profile changes in protein glycosylation associated with human cancer progression and embryonic stem cell differentiation.

Richard P. Woychik, Ph.D. Jane Coffin Childs Fellow

Harvard Medical School

Project Title: An inherited limb deformity created by insertional mutagenesis in tg mouse

Michel R. Wright, Ph.D. Jane Coffin Childs Fellow

Albert Einstein College of Medicine

Project Title: DNA recombination and replication

Barbara Wright, Ph.D. Jane Coffin Childs Fellow

Carlsberg Research Laboratory

Project Title: Effects of glyceric acid and related metabolites on two mutants requiring serine or glycine

Kevin Wu, Ph.D. Jane Coffin Childs Fellow

University of California, Berkeley

Project Title: Structural basis of Doa10-mediated protein quality control at the ER

The endoplasmic reticulum (ER) is a critical organelle for maintaining protein quality control in cells; misfolded proteins are targeted for degradation through the ER-associate degradation (ERAD) pathway. Dr. Kevin Wu will study the ER-membrane bound E3 ubiquitin ligase Doa10 in Dr. Eunyong Park’s lab at the University of California, Berkeley. Doa10 is conserved from yeast to humans and identifies and targets many misfolded proteins for degradation. However, it is unclear how Doa10 recognizes a wide range of client proteins. Dr. Wu will use biochemical and structural approaches to reveal how Doa10 recognizes and processes a range of substrates, and how Doa10 cooperates with other quality control factors to maintain protein homeostasis. Protein misfolding and aggregation are associated with aging and diseases such as neurodegeneration. Thus, Wu’s studies may have implications for developing future therapies to improve protein homeostasis in human disease.

As a graduate student in Dr. James Bardwell’s lab at the University of Michigan, Wu investigated chaperone-mediated protein folding. There, he discovered that weak binding between ATP-independent chaperones enable the refolding of client proteins, whereas stronger binding hinders refolding. Dr. Wu’s background in protein refolding set him up for exploring how Doa10 E3 ubiquitin ligase recognizes unfolded protein targets.

Henry C-P. Wu , M.D., Ph.D. Jane Coffin Childs Fellow

Massachusetts Institute of Technology

Project Title: Lipopolysaccharides in Salmonella

Alan Ming-ta . Wu, Ph.D. Jane Coffin Childs Fellow

University of Wisconsin, Madison

Project Title: Regulation of repression of DNA transcription of early genes

Chung-Hsiun H. Wu, Ph.D. Jane Coffin Childs Fellow

Carnegie Institution for Science

Project Title: Intranuclear organelles that contain snRNPs

Xiaohua Wu, Ph.D. Jane Coffin Childs Fellow

Dana-Farber Cancer Institute

Project Title: Cloning and characterizing the EIA-binding protein p400

Karen Wu, Ph.D. Jane Coffin Childs Fellow

Columbia University

Project Title: The contribution of neuroligin and neurixin diversity to synaptic specificity

Xiaoyang Wu, Ph.D. Jane Coffin Childs Fellow

Rockefeller University

Project Title: Coordinated cytoskeletal dynamics and epidermal polarity: implications in skin cancer

Hao Wu, Ph.D. Jane Coffin Childs - Merck Fellow

Harvard University

Project Title: Dissecting functions of long noncoding RNAs in cardiac progenitors and heart development

Xudong Wu, Ph.D. Jane Coffin Childs Fellow

Harvard Medical School

Project Title: Probing the molecular mechanism of ERAD-L

My research investigates the molecular mechanism of ER-associated degradation (ERAD). Using biochemical and structural tools, my study aims to understand how misfolded proteins in the ER are recognized, retro-translocated out of the ER into the cytosol, and subsequently degraded by proteasome._x000D_
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I was born and grew up in one of the big city in China, Shanghai. After receiving BS in Biology from Fudan University, my strong interest in protein biochemistry brought me overseas to pursue my PhD in molecular biochemistry and biophysics from Yale University. Working in the lab of Karin M. Reinisch, my thesis work focused on solving structures of key regulators of membrane trafficking. Currently, I am doing postdoctoral work supervised by Tom Rapoport, in whose lab I learn new skills in the exciting field of membrane biology. Outside of the lab, I like painting, and enjoy life in Boston with my family and friends.

Wilson C-S. Wu, M.D., Ph.D. Jane Coffin Childs Fellow

Yale University

Project Title: Regulatory roles of synaptic phosphoproteins

Zeba Wunderlich, Ph.D. Jane Coffin Childs Fellow

Harvard Medical School

Project Title: Connecting sequence divergence to quantitative phenotype differences in drosophila

I am currently working on the connection between regulatory region sequence and function by measuring quantitative expression patterns of developmental genes in multiple Drosophila species and creating a biophysical model to interpret these data.

I have always been interested in applying methods from statistics and physics to biological problems. ¬†As an undergraduate at Rutgers University, I majored in molecular biology and statistics and did computational work in a protein NMR lab. ¬†I continued my education in Harvard University’s biophysics program, where I developed mathematical models of a wide variety of biological phenomena, including metabolic networks and protein-DNA interactions. ¬†Following an inspirational summer at the Marine Biological Laboratory¬ís physiology course, I decided to focus my postdoctoral studies on transcriptional regulation, this time combining my computational work with experiments. Outside of my research, I enjoy spending time outside — rowing, running and cross-country skiing.

Gregory A. Wyant, Ph.D. Jane Coffin Childs - HHMI Fellow

Dana-Farber Cancer Institute

Project Title: Unbiased analysis of the mitochondrial permeability transition pore

Heart failure is a common and lethal condition, yet the mechanisms by which the heart fails remains a mystery. Over the past decade, heart failure etiology has shifted from valvular heart disease and hypertension to coronary artery disease. As a result, ischemic cardiomyopathy-symptomatic left ventricular (LV) dysfunction in the setting of coronary artery disease- now accounts for nearly 70% of all heart failure causes in the United States. The exact basis of ischemic cardiomyopathy is unknown; however, identifying molecular changes in the ischemic myocardium and the generation of animal models by which these processes can be studied are an absolute necessity.

Hypoxia-inducible factor (HIF), which consists of a labile ÔÅ° subunit and stable ÔÅ¢ subunit, is master transcription factor that accumulates during hypoxia and activates genes whose products promote cellular survival under ischemic conditions. The HIFÔÅ°ÔÄ†subunit is regulated through prolyl hydroxylation by ÔÅ°-ketoglutarate (ÔÅ°KG) dependent dioxygenases known as EGLNs (also called PHDs). Acute PHD inactivation in the heart has been shown to be protective during acute cardiac ischemia in rodents, and several PHD inhibitory drugs are now in development as tissue protectant molecules. Conversely, chronic PHD inactivation or HIF stabilization itself, both predictable consequences of chronic ischemia, is sufficient to induce the hallmarks of ischemic cardiomyopathy. My work in William Kaelin‚Äôs lab has identified a new mechanism contributing to the pathogenesis of HIF-driven ischemic cardiomyopathy.

Jacqueline R. Wyatt, Ph.D. Jane Coffin Childs Fellow

Yale University

Project Title: snRNA catalyzed splicing in the absence of proteins

James H. Wyche, Ph.D. Jane Coffin Childs Fellow

University of California, Berkeley /
University of California, San Diego

Project Title: Regulation of repression in histidine operon of S. typhimurium

Shiyu Xia, Ph.D. Jane Coffin Childs Fellow

California Institute of Technology

Project Title: Synthetic protein circuits as conditional triggers of anti-tumor immunity

By detecting molecular signatures of cancer cells, synthetic protein circuits delivered as mRNA could specifically kill cancer cells. However, a major hurdle is the inability to deliver circuits to all cancer cells in a tumor. An ideal therapy would both selectively eliminate cancer cells to which circuits are successfully delivered and trigger a broader killing effect on the surrounding tumor. Inflammatory cell death that releases immunostimulatory signals provides an ideal mechanism to achieve these two goals by directly killing on-target cancer cells, as well as indirectly killing off-target cancer cells by activating lymphocyte-mediated anti-tumor immunity. Our goal is to design protein-level circuits capable of identifying cancer cells, executing cell death, and eliciting anti-tumor immunity. We will engineer an input module that senses and amplifies oncogenic signals, design an output module that thresholds these signals and actuates inflammatory cell death, and validate the full input-output circuit using cellular and mouse cancer models. Our research will offer a novel immunotherapy concept that combines synthetic biology approaches with the immunotherapy.

Yu (Brandon) Xia, Ph.D. Jane Coffin Childs Fellow

Yale University

Project Title: Predicting membrane Helix interactome

Mai Xu, Ph.D. Jane Coffin Childs Fellow

Dana-Farber Cancer Institute

Project Title: Biological analysis of intrinsic CBP HAT function

Katherine Xue, Ph.D. Jane Coffin Childs Fellow

Stanford University

Project Title: Adaptation and dispersal in the evolution of microbial communities

The trillions of microbes that live in and on the human body play key roles in health and disease. However, little is known about how microbes evolve in complex communities, even though this evolution can have important consequences for human health. I will study how adaptation and dispersal drive the evolution of antibiotic resistance in microbial communities, both in the human gut microbiome (in vivo) and in experimental, gut-derived microbial communities (ex vivo). First, I will track evolution in the human gut microbiome in a cohort of healthy individuals treated with ciprofloxacin. Using strain-resolved metagenomic sequencing, I will identify selective sweeps and strain replacements to determine how natural microbial communities evolve in response to a disturbance. Next, I will examine how adaptation and dispersal shape the evolution of gut-derived microbial metacommunities. These experimental metacommunities allow me to test how dispersal shapes the rates and mechanisms of adaptation in more controlled, laboratory contexts. Finally, I will study adaptation and transmission in the human gut microbiome by tracking strain transmission in cohabiting individuals before and after antibiotic treatment. This work will combine new computational and experimental approaches to shed light on how microbial communities evolve in the context of human health.

Mingshan Xue, Ph.D. Jane Coffin Childs - HHMI Fellow

University of California, San Diego

Project Title: Circuit analysis of sensory activated neuronal ensembles in mammalian cortex

My current research is focused on understanding the neural circuit mechanism underlying the specific activation of neuronal ensembles by sensory stimuli in the mammalian cortex.

I grew up in a small town in Hunan Province, China. Both my parents are physicians. ¬†In high school, I chanced upon the book, What Mad Pursue by Francis Crick; I was attracted to Dr. Crick¬ís passion for the ¬ìstudy of life,¬î and intrigued by the complexity and sophistication of biological systems. I went on to major in biology at Fudan University.

During my senior year, I became interested in neuroscience, and decided to pursuit my graduate study in the US. My graduate research at Baylor College of Medicine focused on the molecular mechanism of synaptic transmission, the process by which neurons communicate with each other.

Now I am extending my scientific interest into the synaptic mechanisms of neural circuit operation in health and disease. In my free time, I like to watch sports, play with our cats and, occasionally, help my wife in her garden.

Esther VW. Yamada, Ph.D. Jane Coffin Childs Fellow

National Institutes of Health

Project Title: Metabolism of compounds with the acetylene bond

Tepei Y. Yamaguchi, Ph.D. Jane Coffin Childs Fellow

University of California, Berkeley

Project Title: Changes in the core transcriptional machinery during cellular reprogramming

Current research: I am studying changes in the core transcriptional machinery during cellular reprogramming

My interest in studying biology was sparked by my growing up in the countryside of Japan, where I always loved to play in nature. After doing undergraduate work at Kyoto University , I received a master’s degree from Kyoto University in Japan, and a PhD from University of Basel, Switzerland. There, I studied the transcriptional regulation of immune cell differentiation, using mouse genetics with Patrick Matthias at the Friedrich Miescher Institute for Biomedical Research. While completing my PhD study, I developed a strong interest in exploring more mechanistic aspects of the transcriptional regulation dictating cellular identity. To pursue this interest, I joined the lab of Robert Tjian at UC Berkeley. Here, I¬ím enjoying not only the great scientific environment, but also outdoor activities and the unique Bay Area culture.

Gregory A. Yamanaka, Ph.D. Jane Coffin Childs Fellow

Stanford University

Project Title: Signal transduction in vision

Shude Yan, Ph.D. Jane Coffin Childs Fellow

University of California, San Francisco

Project Title: Synthetic feedback shapes MAPK cascade signaling

Liewei Yan, Ph.D. Jane Coffin Childs Fellow

Carnegie Institution for Science

Project Title: Determine how ribosome heterogeneity regulates early embryogenesis

Ribosomes are complex molecular machines that translate mRNAs into proteins and are essential for sustaining life. While the ribosome functions in cellular environments that are markedly diverse, its composition has traditionally been seen as static after assembly. Exciting new studies challenge this concept and provide evidence that organisms assemble different types of ribosomes during development, stress response, or disease. For example, during embryogenesis, zebrafish assemble two types of ribosomes with distinct structures: maternal and somatic. Although this ribosome heterogeneity is predicted to alter protein synthesis, no experimental evidence yet exists to demonstrate this. I will use a multidisciplinary approach to test how changes in ribosome composition affect translation during zebrafish development.

Rebecca Chung-Hui Yang, Ph.D. Jane Coffin Childs Fellow

University of California, San Francisco

Project Title: Identification of neuroprotective genes in Drosophila

Helen H. Yang, Ph.D. Jane Coffin Childs - HHMI Fellow

Harvard Medical School

Project Title: Investigating the role of descending neurons in flexible motor control

A long-standing question is how circuits in the brain control motor output, especially given the flexibility that is a hallmark of motor control. Even a seemingly simple action—such as turning the body—can be executed in different ways. For example, a walking fruit fly performs repeated tight turns while foraging locally but more gradual turns while navigating over long distances. Descending neurons (DNs), serving as the bottleneck connecting the brain to the nerve cord, are well-positioned to implement this type of action selection. Here, I propose to characterize the DNs involved in turning behavior in walking Drosophila. I hypothesize that different DN ensembles control distinct turning modes and are differentially recruited during local search and long-range navigation. To test this hypothesis, I will first identify and characterize DNs that are necessary and/or sufficient to evoke different turning modes. Next, I will use optical recording and electrophysiology to investigate how DN activity correlates with turning mode. Finally, I will examine inputs and outputs of these DNs to gain insight into how they are recruited and how they differentially control the legs. Together, these experiments will establish how an ensemble of parallel neural pathways can precisely shape a complex, adaptable behavior.

Moshe Yaniv, Ph.D. Jane Coffin Childs Fellow

Stanford University

Project Title: Enzyme-tRNA interactions

Zepeng Yao, Ph.D. Jane Coffin Childs Fellow

University of California, Berkeley

Project Title: Sensory integration of taste and smell in drosophila

The senses of taste and smell are intimately related, providing an attractive model to study how sensory inputs are integrated. Using the fruit fly Drosophila melanogaster as a model organism, I have found that a fruit-related odorant promotes ingestion of a moderately palatable compound, indicating that taste smell_x000D_
integration occurs in flies and influences feeding decisions. Furthermore, I have identified a subset of olfactory projections neurons that are taste-responsive, suggesting a possible neural mechanism for taste-smell integration. Here, I propose three specific aims to further investigate how sensory detection of_x000D_
taste and smell is integrated in flies. I will examine how tastes and odors interact at the behavioral level (Aim 1), characterize the neural mechanisms that support taste-smell integration (Aim 2), and investigate the behavioral relevance of such mechanisms (Aim 3). The work proposed here will lead to a better understanding of how sensory information is integrated and leads to decisions and actions, and help inform how such processes may be compromised in patients with cancer and brain disorders.

Geoffrey T. Yarranton, Ph.D. Jane Coffin Childs Fellow

Massachusetts Institute of Technology

Project Title: Role of elongation factors in DNA synthesis

Jiqing Ye, Ph.D., M.D. Jane Coffin Childs Fellow

Harvard Medical School

Project Title: Functional assays and crystallization of TAP