Directory - Jane Coffin Childs Memorial Fund

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Loren R. Snyder, Ph.D. Jane Coffin Childs Fellow

International Laboratory of Genetics and Biophysics (IGB-CNR) /
Institut de Biologie Physico-Chimique, France

Project Title: Mechanism of RNA synthesis by RNA polymerase

Adam Wei Jian Soh, Ph.D. Jane Coffin Childs Fellow

Duke University

Project Title: Determining how basement membranes stretch and recover to support tissues

Dr. Adam Wei Jian Soh will investigate how the basement membrane (BM), a sheet-like extracellular matrix that encloses tissues, stretches in mechanically-active tissues in Dr. David Sherwood’s lab at Duke University. Dr. Soh will use C elegans ovulation as a novel model system for examining BM stretching and recovery. Soh has performed a localization screen and identified candidate proteins that are likely important for BM dynamics. He will follow up on these findings by determining which proteins are functionally important for the stretching and recovery of BMs. Soh hypothesizes that type IV collagen is critical for stretching tissues as genetic defects in this gene lead to vasculature hemorrhaging and muscle dysfunction. This research may also identify novel genes that are critical for tissue support and are mutated in human disease.

Previously, Dr. Soh investigated the mechanics of motile cilia beating as a PhD student in Dr. Chad Pearson‘s lab at the University of Colorado Anschutz Medical Campus. Specifically, he discovered a novel intracellular mechanism involving the cortical cytoskeleton network that regulates cilia beating synchronization. Through this research Soh developed expertise in imaging techniques and cellular biophysics. This experience has prepared Dr. Soh for his current project dissecting basement membrane dynamics.

Joseph E. Sokal, M.D. Jane Coffin Childs Fellow

Yale University

Project Title: Liver fractions with glycogenolytic properties

Olga Sokolova, Ph.D. Jane Coffin Childs Fellow

Brandeis University

Project Title: Electron microscopy of a voltage-gated ion channel

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

Yale University

Project Title: Signals for RNA splicing

Rachel S. Soloff, Ph.D. Jane Coffin Childs Fellow

University of California, San Francisco

Project Title: Protein kinase C in thymocyte selection

Ellen Solomon, Ph.D. Jane Coffin Childs Fellow

Institut Pasteur /
University of California, San Francisco

Project Title: Cell division in E. coli

Ronald L. Somerville, Ph.D. Jane Coffin Childs Fellow

Stanford University

Project Title: Nucleic acids in protein synthesis

Jiarui Song, Ph.D. HHMI-Jane Coffin Childs Fellow

University of Colorado, Boulder

Project Title: G-quadruplex RNA-mediated PRC2 dimerization

Histone methyltransferase PRC2 (Polycomb Repressive Complex 2) silences genes via successively attaching three methyl groups to lysine 27 of histone H3 (H3K27me3). Several research groups including ours demonstrated that PRC2 associates with numerous pre-mRNA and lncRNA transcripts with a strong binding preference for G-quadruplex forming RNA. However, the structural details of their interactions have so far been unclear. My research provides a 3.3Å-resolution cryo-EM structure of a PRC2-RNA ribonucleoprotein complex. Notably, G-quadruplex RNA bridges the dimerization of PRC2 with a symmetric interface comprised of two copies of the PRC2 catalytic subunit EZH2. Especially, EZH2 SET domain is indicated to directly facilitate the RNA-mediated dimerization of PRC2. Interestingly, those residues were previously characterized in the PRC2-nucleosome cryo-EM structure to physically interact with the histone H3 tail and nucleosome DNA. Therefore, I hypothesize that in the dimerized PRC2-RNA complex, RNA inhibits PRC2 activity by limiting H3 tail accessibility to the active site. Overall, my study provides a new perspective of RNA regulation of chromatin modifiers.

Ji-Joon Song, Ph.D. Jane Coffin Childs Fellow

Massachusetts General Hospital

Project Title: Structural studies of chromatin modifier-PRC1

John C. Sonne, M.D. Jane Coffin Childs Fellow

University of Pennsylvania

Project Title: Purine metabolism

Erik J. Sontheimer, Ph.D. Jane Coffin Childs Fellow

University of Chicago

Project Title: TGF-B signaling in C elegans development, RNA biochemistry

Peter Sorger, Ph.D. Jane Coffin Childs Fellow

University of California, San Francisco

Project Title: Regulation of the yeast heat shock transcription factor

Trevor R. Sorrells, Ph.D. Jane Coffin Childs - Merck Fellow

Rockefeller University

Project Title: Motivation in the female mosquito

Female mosquitos seek out hosts for blood meals, a behavior that is required for reproduction and that evolved several times in insect evolution. Host seeking is a persistent behavioral state composed of sequential behaviors such as taking flight, searching, landing, and feeding. It is not known how these behaviors are coordinated nor how this persistent motivational state is signaled in the brain._x000D_
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I propose to study sequential host-seeking behaviors by applying an automated behavior classification system to track multiple mosquitoes in three dimensions as they seek out and feed on a human host. Because of the important role of dopamine in insect decision making, I will use genetic approaches to manipulate dopamine signaling circuits in the mosquito Aedes aegypti. I will assess the effect of these perturbations during host seeking and during an assay simulating host defensive behavior. These experiments will give a description of the role of dopamine signaling in a sustained complex behavior that evolved in the common ancestor of mosquitoes._x000D_
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Robert A. Spangler, M.D. Jane Coffin Childs Fellow

University of Buffalo

Project Title: Membrane permeability

Brian B. Spear, Ph.D. Jane Coffin Childs Fellow

University of Colorado, Boulder

Project Title: Genetic organization of DNA

Thomas Spector, Ph.D. Jane Coffin Childs Fellow

University of Michigan

Project Title: Enzymatic mechanism of molecular oxygen activation

Abraham Spector, Ph.D. Jane Coffin Childs Fellow

Carlsberg Research Laboratory

Project Title: Investigations toward elucidating the structure of the enzymatically active core of ribonuclease

Paul C. Spiegel, Ph.D. Jane Coffin Childs Fellow - Agouron

University of California, Santa Cruz

Project Title: Structural studies of ribosomal translocation

Elias T. Spiliotis, Ph.D. Jane Coffin Childs Fellow

Stanford University

Project Title: Biogenesis of epithelial cell polarity: the SEC 6/8 complex

John L. Spudich, Ph.D. Jane Coffin Childs Fellow

Consiglio Nazionale delle Richerche, CNR /
Harvard University Medical School

Project Title: Purification of an SV40 DNA replicating system

Demetri D. Spyropoulos, Ph.D. Jane Coffin Childs Fellow

University of Utah

Project Title: Generation of mice null for development control genes

Paul A. Srere, Ph.D. Jane Coffin Childs Fellow

Yale University

Project Title: Metabolism of glucose

Mansi Srivastava, Ph.D. Jane Coffin Childs - HHMI Fellow

Whitehead Institute

Project Title: Identification of wound-induced signals by comparing regeneration across diverse animal phyla

Many animal species are able to regenerate missing body parts or even entire body plans. I am using molecular and genomic tools to study regeneration and learn whether regeneration mechanisms in various species were inherited from their common ancestor or if they have evolved independently. Discovering conserved mechanisms might reveal previously unknown but potentially critical aspects of regeneration in animals.

During college, I studied development, regeneration, and asexual reproduction in segmented worms. My graduate work focused on the genomes of early animal lineages such as sea anemones and sponges to learn about early animal evolution. Such comparative genomic analyses have allowed us to infer changes in gene content, gene structure, and genomic organization that accompanied the appearance of animals and their subsequent radiation into phyletic lineages. However, we don¬ít yet understand the functions of the genomic innovations unique to animals.¬† I am now studying the evolution of a particular biological process, focusing on how the functions of a few genes have evolved. For this research, I have returned to my interest in regeneration which, with the help of modern genetic tools, can be studied at molecular and cell biological levels in many species.

Swathi Srivatsa, Ph.D. Jane Coffin Childs Fellow

Harvard Medical School

Project Title: Understanding gut-to-brain signaling through the vagus nerve

The vagus nerve is a key part of the neuroendocrine axis that controls feeding behavior and metabolism. Within the gastrointestinal tract, vagal sensory neurons detect ingested nutrients and mechanical stretch of the stomach, although underlying sensory transduction mechanisms are not understood. Basic questions remain about how ingested food is sensed, and how inputs are relayed centrally to coordinate systemic responses. Unraveling the functions of different vagal sensory neuron types in feeding behavior and metabolism control would provide a basic understanding of gut-to-brain communication mechanisms, and perhaps provide new therapeutic targets to control appetite and help treat metabolic disorders like diabetes, obesity and anorexia._x000D_
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I am working towards characterizing a subpopulation of vagal sensory neurons that express cholecystokinin receptor type- A (CCKAR), a receptor for the gut satiety hormone cholecystokinin (CCK). Using transgenic mice, anatomical tract tracing, calcium imaging and optogenetics I want to understand the structure and function of the neural circuits formed by these sensory neurons. These studies will enable long-term efforts to shed light on the sensory biology of the vagus nerve- from understanding signal transduction mechanisms in the periphery to determining the organization of central inputs that orchestrate behavioral and endocrine responses._x000D_
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Julie St.-Pierre, Ph.D. Jane Coffin Childs Fellow

Dana-Farber Cancer Institute

Project Title: Control of mitochondrial function by PGC-1

Mark A. Stamnes, Ph.D. Jane Coffin Childs Fellow

Memorial Sloan Kettering Cancer Center

Project Title: Isolation and characterization of the SNAP receptor

Martha P. Stark, Ph.D. Jane Coffin Childs Fellow

University of California, San Francisco

Project Title: Activation signals of the unfolded protein response

Louis M. Staudt, M.D., Ph.D. Jane Coffin Childs Fellow

Whitehead Institute

Project Title: Molecular basis of antibody complementarity

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

Johns Hopkins University /
University of California, San Francisco

Project Title: Genetic regulation of RNA tumor virus

Image of Patrick E. Steadman, M.D., Ph.D.

Patrick E. Steadman, M.D., Ph.D. HHMI - Jane Coffin Childs Fellow

Stanford University

Project Title: Cytoplasmic export mechanisms for pathological R-loops

Dr. Patrick Steadman is passionate about neuroscience and the interplay between neurons and glial cells (support cells in the brain) in physiology and disease. During his graduate research, he examined the interaction between these cell types in normal memory consolidation. In his fellowship, Steadman will now investigate how this interplay impacts pediatric low-grade gliomas.

Steadman’s thesis research in Dr. Paul Frankland’s lab at the University of Toronto, focused on the importance of a specialized glial cell, myelin-forming oligodendrocytes, in memory consolidation. He showed that oligodendrogenesis and de novo myelination in the cortex are promoted by learning. Importantly, when he prevented learning-induced increases in oligodendrogenesis, this impaired memory consolidation. Steadman’s results emphasize the role of glial cells in fine-tuning neural circuits for memory consolidation and retrieval.

Now in Dr. Michelle Monje’s lab at Stanford University, Dr. Steadman will continue to examine glial-neuronal interactions, but in the pathological context of pediatric low-grade gliomas. Recent work from the Monje lab demonstrated that gliomas increase neuronal excitability which promotes tumor growth and disrupts normal brain function. Steadman will investigate the molecular mechanisms mediating glioma progression, and test targeted therapies’ impacts on glioma progression and brain function. This research will provide new insight into pediatric gliomas while taking into account the cognitive impact of potential treatments on patients – an important consideration since children with this disease are typically quite young.

Patricia S. Steeg, Ph.D. Jane Coffin Childs Fellow

National Institute of Dental Research and National Cancer Institute

Project Title: Reversal of phenotype of transformed fibroblasts

Kristan Steffen, Ph.D. Jane Coffin Childs Fellow

Salk Institute

Project Title: Cell non-autonomous modulation of electron transport chain-mediated lifespan extension

Eric J. Steinmetz, Ph.D. Jane Coffin Childs Fellow

University of Wisconsin, Madison

Project Title: RNA dynamics in the spliceosome assembly cycle

Thomas A. Steitz, Ph.D. Jane Coffin Childs Fellow

Medical Research Council (MRC),UKRI

Project Title: X-ray diffraction

Joan A. Steitz, Ph.D. Jane Coffin Childs Fellow

Medical Research Council (MRC),UKRI

Project Title: Sequencing of tRNA

Paul W. Sternberg, Ph.D. Jane Coffin Childs Fellow

University of California, San Francisco

Project Title: Regulation of HO gene of S. cerevisiae

Donté A. Stevens, Ph.D. Jane Coffin Childs Fellow

The Scripps Research Institute

Project Title: Towards a novel tauopathy therapeutic: harnessing biomolecular condensates for targeted protein degradation.

Tauopathies are diseases such as Alzheimer’s that are characterized by the aggregation of tau protein. Unfortunately, no disease-modifying therapies currently exist for tauopathies, and the impact of these diseases will increase as the global population trends towards an aging demographic.

Dr. Alex Stevens will investigate a novel mode for treating tauopathies in Dr. Keren Lasker’s lab at the Scripps Research Institute. Autophagy-based degradation methods are making progress, yet a hallmark of tauopathies is that these solid tau aggregates resist degradation. To circumvent this issue, Dr. Stevens will engineer biomolecular condensates to clear tau aggregates. Stevens’ research will set the foundation for next generation tauopathy therapies and provide a general framework using biomolecular condensates to modulate pathological events.

Stevens investigated how viruses hijack cellular transport mechanisms during his Ph.D. research in Dr. Samara Reck-Peterson’s lab at the University of California, San Diego. By exploring the conflicts between viruses and the host intracellular transport machinery, Stevens discovered a previously unknown transport mechanism that potentiates the innate immune response. His research provides insight into how cells mount a defense against infecting viruses and highlights the important role of cellular transport in this process. Now, Stevens will attempt to rationally hijack autophagy to enable degradation of aggregated tau.

Emerson Stewart, Ph.D. Jane Coffin Childs Fellow

Stanford University

Project Title: Molecular mechanisms of presynaptic assembly and maintenance in C. elegans neurons

The human brain is a highly ordered structure, consisting of billions of neurons linked through trillions of intercellular connections. Among the most powerful computational machines known to man, the human brain controls everything from our ability to perceive the world around us to higher order functions involved in learning and memory. At the heart of the brain’s processing power lies the synapse.

Synapses are specialized subcellular structures that mediate communication between neurons, thereby dictating information flow within the nervous system. Numerous proteins involved in synapse formation have been identified, yet how active zone and synaptic vesicle proteins coalesce into highly ordered macromolecular complexes remains a fundamental question in neurobiology. I am interested in elucidating the molecular underpinnings that support synapse formation and maintenance.

To this end I will use the Hermaphrodite Specific Neuron in C. elegans to examine how synapses are formed during development and maintained throughout the lifespan of the organism. Through a combinatorial approach employing RNAi and forward genetic screens as well as fluorescent microscopy I will take advantage of the inherent benefits of the C. elegans system to study conserved processes of synapse formation in the context of an intact organism.

David J. Stillman, Ph.D. Jane Coffin Childs Fellow

Medical Research Council (MRC),UKRI

Project Title: Transcriptional regulation of yeast HO Gene

Dan T. Stinchcomb, Ph.D. Jane Coffin Childs Fellow

University of Colorado, Boulder

Project Title: DNA replication and transformation in C elegans

Anne Stockell Hartree, Ph.D. Jane Coffin Childs Fellow

University of Cambridge, England

Project Title: Relation of protein structure to function

Elizabeth A. Stone, Ph.D. Jane Coffin Childs Fellow

University of California, Berkeley

Project Title: Discovery and Synthesis of novel anticancer drugs via enzyme engineering

The discovery of novel antitumor drugs requires the development of new methods to synthesize molecules of increasing diversity and complexity to meet the challenges of drug efficacy and safety. Biocatalysis provides an attractive strategy to perform chemical reactions under mild and sustainable conditions. The Chang Lab has recently discovered a family of radical halogenases that perform the regio- and stereoselective chlorination of unactivated, aliphatic C–H bonds within several amino acid substrates. Despite the synthetic utility of organohalides, there are limited biosynthetic and chemical methods for the selective chlorination of unfunctionalized alkanes beyond this example.

Using mechanistically-guided protein engineering, my research aims to expand the substrate and reaction scope of these enzymes to produce noncanonical amino acids bearing versatile functional group handles, including halogens or azide. These synthetic residues will then be incorporate into biological molecules of interest, such as known anticancer peptides, and can be further functionalized to access diverse, cyclic structures. Overall, this strategy provides a fully biosynthetic method for producing novel analogs of anticancer peptides with the goal of discovering improved drugs.

John E. Stouffer, Ph.D. Jane Coffin Childs Fellow

University of Glasgow

Project Title: Biogenic aspects of phenol oxidation

David C. Straney, Ph.D. Jane Coffin Childs Fellow

Cornell University

Project Title: Gene control elements in P450 pisatin detoxification

Margaret M. Stratton, Ph.D. Jane Coffin Childs - HHMI Fellow

University of California, Berkeley

Project Title: The molecular mechanism of CaMKII activation by specific calcium-spike frequencies

Sidney Strickland, Ph.D. Jane Coffin Childs Fellow

Rockefeller University

Project Title: Membrane proteins

Michael Strong, Ph.D. Jane Coffin Childs Fellow - Fidelity Foundation

Harvard Medical School

Project Title: Development of integrated genomic maps

Image of Shannon L. Stroschein Stevenson, Ph.D.

Shannon L. Stroschein Stevenson, Ph.D. Jane Coffin Childs Fellow

University of California, San Francisco

Project Title: Host-pathogen interactions of Candida and Drosophila

Kevin Struhl, Ph.D. Jane Coffin Childs Fellow

Medical Research Council (MRC),UKRI

Project Title: Expression of yeast and nematode genes in yeast cells

Bethany S . Strunk, Ph.D. Jane Coffin Childs Fellow

University of Michigan

Project Title: Elucidating mechanistic defects associated with dysregulation of a phosphatidylinositol signaling lipid

Mutations in Fig4 cause the incurable neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and CharcotMarie-Tooth Syndrome (CMT) through dysregulation of phosphatidylinositol (3,5)-bisphosphate (PI3,5P2). A molecular understanding of the mechanisms by which Fig4 regulates both the transient production and rapid turnover of this signaling lipid will be essential for devising therapies. Fig4 is the lipid phosphatase responsible for dephosphorylating PI3,5P2 at the 5 position to produce phosphatidylinositol 3-phosphate (PI3P). Paradoxically, conserved residues in the yeast Fig4 phosphatase active site are required to activate the lipid kinase catalyzing the addition of the very phosphate it hydrolyses. This suggests an internal mechanism for preventing uncontrolled elevation of PI3,5P2 in the absence of the activity required to restore it to basal levels. The research proposed here will use a yeast model to elucidate the conserved mechanisms by which Fig4 controls both the synthesis and turnover of PI3,5P2 and uncover which of these mechanisms are disrupted by disease related mutations.