Directory - Jane Coffin Childs Memorial Fund

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Jenelle Wallace, Ph.D. Jane Coffin Childs Fellow

University of California, San Francisco

Project Title: Evolution of human-speciﬁc neuronal activity-dependent gene regulation

New experiences elicit novel patterns of neural activity, prompting changes in gene expression that underlie learning. However, most studies of human brain evolution focus on species differences in baseline gene expression. Activity-dependent enhancers that control neuronal gene expression could represent an unexplored substrate for the evolution of human cognitive specializations. To examine the evolution of the activity-regulated genome in the human lineage, I will utilize primary neurons from human and macaque as well as induced pluripotent stem cell-derived neurons from human and chimpanzee to create cortical circuits in vitro and stimulate activity with physiological paradigms. I will measure coordinated changes in chromatin accessibility and gene expression in single cells to discover human-divergent neuronal activity-regulated elements (hDAREs). A CRISPRi screen will allow me to test hDARES to determine which are human-specific activity-dependent enhancers. To begin to investigate the consequences of evolutionary alterations for brain plasticity, I will model a human-specific deletion of a candidate activity-dependent enhancer regulating a gene with known roles in restricting spine growth in mice. Utilizing in vivo imaging to measure synapse formation during motor learning, I will test the hypothesis that activity-dependent expression of this gene, conserved between mice and chimpanzee, may inhibit learning-induced synapse formation and that the human-specific deletion may relieve this plasticity brake. Combining evolutionary genetics and systems neuroscience approaches will lay the groundwork for exploring this new dimension of human brain evolution.

Alexander C. Wallace, M.D. Jane Coffin Childs Fellow

Yale University

Project Title: Comparing the growth of tumors in such media to those transplanted in the anterior chamber

Michael Wallis, Ph.D. Jane Coffin Childs Fellow

Johns Hopkins University

Project Title: Protein biochemistry and structure

Liling Wan, Ph.D. Jane Coffin Childs Fellow

Rockefeller University

Project Title: Functional and mechanistic study of histone crotonylation in leukemias

My research interest is to understand the epigenetic mechanisms that drive cancer development. With a focus on a few newly discovered histone posttranslational modifications, I am currently studying their functional roles and mechanisms in cellular differentiation and oncogenesis._x000D_
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I spent my first 18 years in Hainan, a beautiful island located in the South China Sea before I moved to Beijing where I received B.S. degree in Biology from Tsinghua University. Initial exposure to scientific research at Tsinghua got me fascinated about science and promoted me to pursue graduate studies at Princeton University, where, in Dr. Yibin Kangs laboratory, I investigated the genetic causes underlying cancer initiation and metastasis. Appreciating that the interplay between genetic and epigenetic regulations is important in cancer development, I joined the laboratory of Dr. David Allis as a postdoc fellow where I continue studies in cancer research with a different focus on epigenetic causes of cancer. Outside of the lab, I enjoy the outdoors, spending time with family and friends, and trying delicious food.

Zhiping Wang, Ph.D. Jane Coffin Childs Fellow

University of California, San Diego

Project Title: Characterization of new axon regeneration regulation pathways

Current research: ¬†I am interested in dissecting the genetic basis of adult axon regeneration in the model organism C. elegans.

My first sixteen years were spent happily in a small town in southeastern China. I didn¬ít have much experience in biological sciences until I became an biology major at Tsinghua University. In a neuroscience course, a professor introduced to us the fantastic structure of neurons and the intriguing molecular mechanisms underlying how neurons encode external information and learn. From that moment, I was entranced by this field, and chose it as my career path. I came to Michael Ehlers¬ís lab at Duke University to study the molecular mechanisms of long term plasticity in hippocampal neurons. There, I discovered that an unconventional actin motor is a critical LTP-mediating player. Subsequently, I joined Yishi Jin¬ís lab as a postdoctoral researcher to explore the genetic mechanisms of adult axon regeneration in C. elegans. Outside the lab, I am a super soccer fan and love fresh-water fishing. My dreams are to watch a Derby game between FC Barcelona and Real Madrid at Camp Nou and to catch a 20-pound large-mouth bass.

Siyuan Wang, Ph.D. Jane Coffin Childs Fellow

Harvard University

Project Title: Chromatin imaging with STORM-FRET labels

My current research in Professor Xiaowei Zhuang‚Äôs lab at Harvard University focuses on the development and application of super-resolution light microscopy techniques to the study of chromatin organization. In particular, I am interested in the spatial organization of DNA in compact chromatin domains during the interphase.

My graduate research, co-advised by Professor Ned Wingreen and Professor Joshua Shaevitz at Princeton University, presented a series of discoveries regarding the physical properties, dynamics, and organization of the bacterial cytoskeleton and cell wall, including: 1) the mechanical contribution of bacterial cytoskeleton to cellular integrity; 2) the motion of bacterial cytoskeleton driven by cell wall synthesis; 3) the chiral organization and growth dynamics of cell wall in rod-shaped bacteria, derived from the spatial pattern of cytoskeleton; and 4) a possible mechanism for different cytoskeleton components to self-organize into distinct spatial patterns. My dissertation won the 2011 Award for Outstanding Doctoral Thesis Research in Biological Physics from American Physical Society.

Yuxiao Wang, Ph.D. HHMI-Jane Coffin Childs Fellow

University of California, San Francisco

Project Title: Mechanisms of mitotic spindle positioning by cortical dynein

During mitosis, the position of the spindle determines the size, the relative orientation and the developmental fate of daughter cells. The spindle is positioned by a pulling force generated by cortically localized dynein and exerted on astral microtubules that are connected to the spindle poles. Dynein is anchored to the cell cortex by the protein NuMA and activated to pull on the end of microtubule, the mechanism of which remains unknown. To investigate this, we will first systematically define and characterize the interaction between NuMA and dynein using purified components. Next we will reconstitute the microtubule end capturing and pulling force generation activities of dynein using a microfabricated barrier based system, in which the regulation of dynein by NuMA will be investigated. In addition, we will determine the crystal structure of the complex of NuMA-dynein binding regions to reveal the structural basis for their interactions. Finally, the overall structure of full-length NuMA will be examined using electron microscope and the functional significance of NuMA oligomerization will be determined. Together our proposed study will provide a mechanistic understanding of how dynein is recruited and activated by NuMA to generate cortical pulling force for mitotic spindle positioning.

Chong Wang, Ph.D. Jane Coffin Childs Fellow

Harvard University

Project Title: Imaging protein translation at the single-molecule level in living cells

Translation mediates the flow of genetic information encoded in mRNAs to proteins and can be regulated by many factors, contributing an essential part to the cellular gene expression regulation program. To understand how translation are influenced by various factors such as extracellular stimuli, cell metabolic states, subcellular localizations and so on, a method that could reveal the timing, location and level of translation activity on a defined single mRNA transcript in living cells would be invaluable. My research focuses on the development of a fluorescence imaging based method to study translation on a single mRNA transcript in living cells. I am going to use this method to study translation initiation and elongation under different conditions and at different subcellular compartments, such as neuronal dendrites and axons, to obtain previously unavailable information of translation dynamics.

Boyuan Wang, Ph.D. Jane Coffin Childs Fellow

Massachusetts Institute of Technology

Project Title: Probing the role of peptidoglycan in establishing bacterial cell polarity

Yu Wang, Ph.D. HHMI-Jane Coffin Childs Fellow

Stanford University

Project Title: Neural mechanism of behavioral exhaustion

Focusing on a task can often leave us exhausted despite low physical exertion. Dr. Yu Wang is investigating the source of this type of behavioral exhaustion. Building off her thesis research on neural sensing of peripheral metabolic states, she’s primed to make key insights into the brain’s metabolic deficiencies that may lead to our fatigue.

Wang developed her expertise in the neural integration of metabolic states during her Ph.D. research in Dr. Ardem Patapoutian’s and Dr. Li Ye’s labs at The Scripps Research Institute. Specifically, she was interested in how sensory neurons regulate peripheral metabolism, metabolic processes that occur in tissues and organs outside of the central nervous system, and how these neurons coordinate intracellular energy use to sustain activity. Wang demonstrated that somatosensory neurons enervate adipose tissue and modulate adipocyte function by acting as a break on the sympathetic system. Interestingly, she found that the mechanoreceptor PIEZO2 is highly expressed in these neurons, and is required for their brake-like function. Collectively, her research has provided keen insight into the interplay between neural function and peripheral metabolic states.

As a postdoc in Dr. Karl Deisseroth’s lab at Stanford University, Wang will examine the neural mechanisms of behavioral exhaustion. She hypothesizes that repetitive behaviors deplete local energy resources in specific brain regions, ultimately leading to behavioral exhaustion. Wang will combine different mouse models with repetitive behaviors, and assess metabolic and energetic states using metabolomics and imaging. Wang’s studies will provide novel insight into behavioral fatigue, and may inform on better intervention strategies.

Jean Y-J. Wang, Ph.D. Jane Coffin Childs Fellow

Massachusetts Institute of Technology

Project Title: Characterization of the A-MuLV transforming genotype

Gary E. Ward, Ph.D. Jane Coffin Childs Fellow

University of California, San Francisco

Project Title: Mechanism of action of maturation promoting factor

Richard L. Ward, Ph.D. Jane Coffin Childs Fellow

Max-Planck Institute

Project Title: Gene order and translational regulation of the phage M12

Pamela J. Ward, Ph.D. Jane Coffin Childs Fellow

University of Glasgow

Project Title: Biosynthesis of adrenocortical steroids

Joshua J. Warren, Ph.D. Jane Coffin Childs Fellow

Duke University

Project Title: Structural Biology of human mismatch repair

Richard AJ. Warren, Ph.D. Jane Coffin Childs Fellow

Massachusetts Institute of Technology

Project Title: The mechanism of catabolite repression with specific reference to histidine degradation in Salmonella Typhimurium

Clare M. Waterman, Ph.D. Jane Coffin Childs Fellow

University of North Carolina, Chapel Hill

Project Title: Cytoplasmic transport in Drosophila egg chambers

Image of Hannah K. Wayment-Steele, Ph.D.

Hannah K. Wayment-Steele, Ph.D. Jane Coffin Childs Fellow

Brandeis University

Project Title: Timing molecular interactions in high throughput via a polymerase stopwatch

Deep learning methods have revolutionized structural biology by accurately predicting single structures of proteins and protein-protein complexes. However, biological function is rooted in a protein’s ability to sample different conformational substates, and disease-causing point mutations are often due to population changes of these substates. This has sparked immense interest in expanding the capability of algorithms such as AlphaFold2 (AF2) to predict conformational substates. We demonstrate that clustering an input multiple sequence alignment (MSA) by sequence similarity enables AF2 to sample alternate states of known metamorphic proteins, including the circadian rhythm protein KaiB, the transcription factor RfaH, and the spindle checkpoint protein Mad2, and score these states with high confidence. Moreover, we use AF2 to identify a minimal set of two point mutations predicted to switch KaiB between its two states. Finally, we used our clustering method, AF-cluster, to screen for alternate states in protein families without known fold-switching, and identified a putative alternate state for the oxidoreductase DsbE. Similarly to KaiB, DsbE is predicted to switch between a thioredoxin-like fold and a novel fold. This prediction is the subject of ongoing experimental testing. Further development of such bioinformatic methods in tandem with experiments will likely have profound impact on predicting protein energy landscapes, essential for shedding light into biological function.

Bailey A.T. Weatherbee, Ph.D. Jane Coffin Childs Fellow

Cincinnati Children's Hospital

Project Title: Multifunctional RNA-binding transcription factors coordinate cell states in development

Human development at the earliest stages is a complicated process with many intrinsic and extrinsic cell signals. For her fellowship, Dr. Bailey Weatherbee will investigate the molecular mechanisms of lineage-defining transcription factors that enable early embryonic development.

During her Ph.D. research in Dr. Magdalena Zernicka-Goetz’s lab at the University of Cambridge, Weatherbee developed a cellular model of the human post-implantation embryo. By combining various types of stem cells made by turning on certain genes, she created cell clusters that mimic important stages of early embryo development. Furthermore, Weatherbee used cell models and embryos to investigate the requirement of specific signaling pathways for different cell types in early development. These studies are a major step forward in modeling the earliest steps in embryonic development and will enable numerous follow-up studies by the broader scientific community.

Now, in Dr. Aaron Zorn’s lab at Cincinnati Children’s Hospital, Weatherbee will investigate the molecular mechanisms of two critical lineage-defining transcription factors (TFs). She hypothesizes that in addition to their canonical DNA-binding activities, binding to RNA is also crucial for their function. Weatherbee will use cell and animal models to evaluate the developmental significance of TF-RNA interactions and identify partner proteins that mediate their function. Since mutations that impact RNA regulation occur in several congenital diseases and cancers, Weatherbee anticipates that her findings will inform on novel therapeutic strategies to treat these conditions.

Stephanie J. Webb, Ph.D. Jane Coffin Childs Fellow

University of Edinburgh

Project Title: Analysis of apoptosis using a cell-free assay

Michel J. Weber, Ph.D. Jane Coffin Childs Fellow

Harvard Medical School

Project Title: Glial factor controlling neuroblasts differentiation

Lawrence D. Weber, Ph.D. Jane Coffin Childs Fellow

Massachusetts Institute of Technology

Project Title: DNA Replication

Liang Meng Wee, Ph.D. Frederick M. Richards-Jane Coffin Childs Fellow

University of California, Berkeley

Project Title: RNA, ribosome and RNA polymerase: three molecules at a time

Transcription by RNA Polymerase and translation by the Ribosome are two fundamental and important processes that shape cellular identity. Mutations that disrupt these processes can result in disease such as cancer. We strive to understand the underlying mechanisms of transcription and translation using optical tweezer. This single molecule technique allows us to monitor the actions of individual RNA Polymerase and the ribosome in real time that are often scored as averages in bulk measurements. We currently aim to scrutinize the activities of these molecular motors when coupled in the same reaction. The coupling between RNAP polymerase and the ribosome, which occurs in vivo in E. coli., constitutes an additional layer to control gene expression. A deeper understanding of both transcription and translation either alone or coupled will open up new ideas to curb or to cure diseases that stem from a malfunction in these process.

Kevin M. Weeks, Ph.D. Jane Coffin Childs Fellow

University of Colorado, Boulder

Project Title: Mechanisms of protein facilitated RNA catalysis

Andrew D. Weems, Ph.D. Jane Coffin Childs Fellow

University of Texas Southwestern

Project Title: Bleb-nucleated signaling scaffolds in metastasis-prone melanoma cells

C. Timothy Wehr, Ph.D. Jane Coffin Childs Fellow

University of California, Davis

Project Title: Structure and assembly of bacterial ribosomes

Hilla Weidberg, Ph.D. HHMI-Jane Coffin Childs Fellow

Massachusetts Institute of Technology

Project Title: Aneuploidy effect on protein homeostasis

Martin Weigert, Ph.D. Jane Coffin Childs Fellow

Salk Institute for Biological Studies

Project Title: Genetic mechanisms that control the production and specificity of antibodies

Ted A. Weinert, Ph.D. Jane Coffin Childs Fellow

University of Washington

Project Title: Molecular analysis of cdc15 in chromosome segregation

Caleb Weinreb, Ph.D. Jane Coffin Childs Fellow

Harvard Medical School

Project Title: Unified model of social processing in prefrontal cortex

I study the deep statistical structure of behavior to learn how it is shaped by ongoing brain activity. The purpose of the central nervous system is to coordinate an animal’s actions in space and time. The power of mammalian brains is evident in the variety and expressiveness of their behavior, yet it is precisely these qualities that make the behavior difficult to annotate and record – steps that are prerequisite for modern data analysis. As a consequence, neuroscience has mostly been limited to a narrow set of behaviors and well-defined tasks. This limitation is especially severe for the study of social behavior, in which the spontaneous actions and reactions of two interacting animals created an added level of complexity.

Recently, the advent of new tools in machine learning have made it possible to quantify behavior with much greater precision and richness. My research focuses on creating new tools for behavior measurement and applying them to rodent social behavior, with the specific goal of understanding how social interaction is shaped by the prefrontal cortex.

George M. Weinstock, Ph.D. Jane Coffin Childs Fellow

Stanford University

Project Title: In vitro replication of col E1 DNA

Michael P. Weir, Ph.D. Jane Coffin Childs Fellow

University of California, San Francisco

Project Title: Effect of protein synthesis inhibition on transcript localization

Robert M. Weis, Ph.D. Jane Coffin Childs Fellow

University of California, Berkeley

Project Title: Adaptation of E. Coli and S. typhimurium to chemostatic stimuli

John W. Weisel, Ph.D. Jane Coffin Childs Fellow

Brandeis University

Project Title: Structure of fibrinogen

Herbert L. Weith, Ph.D. Jane Coffin Childs Fellow

Medical Research Council (MRC),UKRI

Project Title: Sequence analysis of high molecular weight RNA from oncogenic viruses

Sandra E. Wells, Ph.D., J.D. Jane Coffin Childs Fellow

University of California, Berkeley

Project Title: Poly(A)-dependent control of translation initiation

Janet M. Wenzlau, Ph.D. Jane Coffin Childs Fellow

University of Texas Southwestern Medical Center

Project Title: Sterol repressor: genetic and biochemical analysis

Paul D. Wes, Ph.D. Jane Coffin Childs Fellow

University of California, San Francisco

Project Title: Specificity in G protein signal transduction

Ann H. West, Ph.D. Jane Coffin Childs Fellow

University of Medicine and Dentistry of New Jersey

Project Title: Activation of a bacterial signal transduction protein

Barbara C. Westmoreland, Ph.D. Jane Coffin Childs Fellow

Harvard Medical School /
Colorado State University

Project Title: DNA transmethylation

Kenneth P. Wheeler, Ph.D. Jane Coffin Childs Fellow

University of Michigan

Project Title: Transport systems and amino acid transport

Kalpana P. White, Ph.D. Jane Coffin Childs Fellow

Yale University

Project Title: Embryonic determination and differentiation in Drosophila

Raymond L. White, Ph.D. Jane Coffin Childs Fellow

Stanford University

Project Title: DNA structure of Drosophila

Sidney W. Whiteheart, Ph.D. Jane Coffin Childs Fellow

Princeton University

Project Title: Role of NSF attachment protein in Golgi transport

Aaron T. Whiteley, Ph.D. Jane Coffin Childs Fellow

Harvard Medical School

Project Title: Identifying novel nucleotide second messengers from mammals using bacteria

Nucleotide second messengers are crucial for development and signaling in both humans and bacteria. Nucleotide-centric pathways in human cells are targets of therapeutic interventions for cancer and diabetes, but signal regulation is complex and remains poorly understood. My work reconstructs mammalian nucleotide signaling in bacterial systems, creating the transformative opportunity to leverage bacterial genetics to uncover how these pathways are mechanistically regulated. Future findings from this work will enhance our understanding of known and previously uncharacterized cell signals in eukaryotes and prokaryotes._x000D_
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Prior to my postdoctoral work, I earned my Ph.D. in Daniel A. Portnoy’s Lab, at the University of California, Berkeley. There, I worked on essential genes and virulence regulation in the bacterial pathogen Listeria monocytogenes.

James B. Whitley, Ph.D. Jane Coffin Childs Fellow

Rutgers University

Project Title: Population Codes and Communication Subspaces in Motor Control

James Whitley, Ph.D. has always been a fan of the underdog, and he notes that in neuroscience this tag applies broadly to any structure outside of the cortex. In his Ph.D., he showed that these regions do more than pass information along. As a Jane Coffin Childs Fellow, he will now study the brainstem, asking whether it plays a sophisticated role in filtering motor commands.

Historically the thalamus has been seen as a passive relay conveying sensory information to the cortex. Whitley’s graduate research in Martha Bickford’s lab at the University of Louisville challenged this passive view and established a more active, regulatory role for two visual thalamic nuclei. First, he demonstrated that the dorsal lateral geniculate nucleus enhances the flow of visual information following gaze shifts. Then, Whitley revealed an integrative role for the pulvinar nucleus whereby top-down and bottom-up signals are processed in the same neuron.

As Whitley has learned and discovered more about how information is transferred between different regions of the brain, he’s come to the realization that traditional models fail to account for the diversity of behaviors and limit functional flexibility. In Ian Oldenburg’s lab at Rutgers University, Dr. Whitley will examine information transfer between the cortex and the brain stem. He thinks motor commands may be represented as patterns of activity across groups of neurons, and he will test this idea using multiple methods. His goal is a better overall understanding of motor control and movement disorders.