Directory - Jane Coffin Childs Memorial Fund

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Caroline E. Shamu, Ph.D. Jane Coffin Childs Fellow

Harvard University

Project Title: Re-export of proteins of the endoplasmic reticulum membrane into the cytosol

Lucille Shapiro, Ph.D. Jane Coffin Childs Fellow

Albert Einstein College of Medicine

Project Title: Mechanisms of mitochondrial replication

James A. Shapiro, Ph.D. Jane Coffin Childs Fellow

Institut Pasteur /
Harvard University

Project Title: Regulation of growth; regulation of DNA synthesis in E. coli

David M. Shechner, Ph.D. Jane Coffin Childs - HHMI Fellow

Harvard University /
Broad Institute

Project Title: Structure and function of large non-coding RNAs regulated by p53

Efrat Shema-Yaacoby, Ph.D. Jane Coffin Childs Fellow

Massachusetts General Hospital

Project Title: Epigenetic events in cancer

Koning Shen, Ph.D. Jane Coffin Childs Fellow

University of California, Berkeley

Project Title: Defining the protective role of the mitochondrial stress response in aging

Aging is a risk factor for nearly every chronic disease, and organismal health in aging and age-related disorders is increasingly linked to mitochondrial health. A key contributor to age-related mitochondrial dysfunction is the accumulation of misfolded proteins (or proteotoxic stress). Recent evidence has shown how proteotoxic stress can activate the unfolded protein response in mitochondria (UPRmt), a conserved stress response pathway critical for regulating longevity. However, the molecular mechanisms underlying UPRmt activation and lifespan extension during aging remain unknown. The objective of this proposal is to_x000D_
identify a framework for how mitochondria recognize and respond to proteotoxic stress, which will inform how stress response mechanisms become compromised during aging. First, we will investigate how age associated proteotoxic stress activates the UPRmt and how this mechanism becomes compromised during aging. Secondly, we will conduct a focused RNAi screen to discover novel downstream effectors of the UPRmt that are essential for protecting lifespan upon proteotoxic stress. By establishing the relationship between the UPRmt and proteotoxic stress in aging, we will gain a fundamental understanding of the molecular basis of mitochondrial aging. This will establish new realms of therapeutic intervention that directly target the underlying cause of nearly every chronic disease – getting older.

Zhongzhou Shen, Ph.D. Jane Coffin Childs Fellow

Cleveland Clinic Foundation

Project Title: Eosinophils, DNA damage and breast cancer

Jingshi Shen, Ph.D. Jane Coffin Childs Fellow

Columbia University Medical Center

Project Title: Regulation of exocytosis

Michael M. Shen, Ph.D. Jane Coffin Childs Fellow

Harvard Medical School

Project Title: Molecular analysis of chromosomal imprinting in mice

Thomas E. Shenk, Ph.D. Jane Coffin Childs Fellow

Stanford University

Project Title: Nature of SV40-induced T antigen

Kelly A. Shepard, Ph.D. Jane Coffin Childs Fellow

University of California, San Francisco

Project Title: Biochemical analysis of mRNA localization in yeast

Madeline E . Sherlock, Ph.D. Jane Coffin Childs Fellow

University of Colorado, Anschutz Medical Campus

Project Title: Structural basis for noncanonical translation initiation in viruses

My postdoctoral research is focused on structured viral RNAs involved in enhancing translation of viral proteins. Some of the RNAs I‚Äôm studying are able to induce a reinitiation event within the viral RNA genome through specific interactions with the ribosome. My research focuses on the determining the molecular interactions that enable this RNA structure to promote translation activity at downstream open reading frames following a translation termination event. Another set of RNAs I‚Äôm studying are found primarily in plant viruses and mimic cellular tRNAs. Previous and ongoing studies in the Kieft lab aim to determine how different examples of these tRNA-like structures fold, the structural and functional differences between different classes and subtypes, and how these RNAs enhance viral translation.

Lisa M. Shewchuk, Ph.D. Jane Coffin Childs Fellow

University of Oregon

Project Title: Crystallographic studies of the BirA protein

Christine K. Shewmaker, Ph.D. Jane Coffin Childs Fellow

National Institute for Medical Research

Project Title: Molecular mechanisms in the B-thalassemias

Honglue Shi, Ph.D. HHMI - Jane Coffin Childs Fellow

University of California, Berkeley

Project Title: Predicting the speed and accuracy of CRISPR-Cas genome editing

CRISPR-Cas enzymes are versatile tools for gene editing and research applications such as transcriptional regulation and imaging. The speed and accuracy of CRISPR-Cas enzymes are crucial, yet how they identify a unique ~ 20-base-pair target within billions of base pairs in the genome is still unclear. Dr. Honglue Shi aims to obtain a more quantitative and predictive understanding of how natural and engineered CRISPR-Cas enzymes rapidly and accurately target specific DNA sequences in Dr. Jennifer Doudna’s lab at the University of California, Berkeley. Shi will use structure-guided biochemistry to develop a kinetic model for CRISPR-Cas9 search speed and accuracy. He will then test the generality of the model on additional CRISPR enzymes and ancestral RNA-guided TnpB enzymes. This research is fundamental to understanding both the evolutionary history of RNA-guided enzymes and the utility of these systems for genome editing. In the future, these results will enable predictions and design of genome editing functions that are not possible or practical today and will greatly accelerate the field as well as the precision and outcomes of next-generation genome editing tools.

As a Ph.D. student in Dr. Hashim Al-Hashimi’s lab at Duke University, Shi focused on the development of biophysical approaches such as NMR spectroscopy to extend the description of nucleic acids from static structures to dynamic ensembles, which results in a deeper and more predictive understanding of how nucleic acids are being recognized by other biomolecules. Having developed this expertise in nucleic acid biophysics and perspectives in dynamic ensembles, Dr. Shi is ready to elucidate the properties that define the best genome editors in Dr. Doudna’s lab.

Ellen K. Shibuya, Ph.D. Jane Coffin Childs Fellow

Harvard Medical School

Project Title: Activation of cdc 2/cyclin kinase during meiosis in the surf clam

Ali Shilatifard, Ph.D. Jane Coffin Childs Fellow

Oklahoma Medical Research Foundation

Project Title: Role of phosphorylation in eukaryotic mRNA synthesis

Jeoung-Sook Shin, Ph.D. Jane Coffin Childs Fellow

Yale University

Project Title: Multivesicular bodies in dendritic cell function

Myung K. Shin, Ph.D. Jane Coffin Childs Fellow

Princeton University

Project Title: Melanocyte development in mice

David M. Shore, Ph.D. Jane Coffin Childs Fellow

Medical Research Council (MRC),UKRI

Project Title: Structure and regulation of yeast mating-type genes

Ellen L. Shrock, Ph.D. Jane Coffin Childs Fellow

University of Washington

Project Title: Decoding the Structural Basis of Immunogenicity

Dr. Ellen Shrock envisions a future where novel therapeutics are not seen as dangerous by the immune system. While studying the immune response to SARS -CoV2 in her graduate work, she recognized that even different individuals responded in the same way to the virus. In her fellowship, Shrock is systematically characterizing immunogenicity, the ability of a substance to provoke an immune response, and training models to predict antibody recognition, with the long-term goal of avoiding such features in protein therapeutics.

During her thesis research in Dr. Stephen Elledge’s lab at Harvard Medical School, Shrock studied antibodies from people who had COVID-19 and found they targeted over 800 parts of the virus. She also showed that some parts of these antibodies are built into our genes and help the immune system recognize viruses quickly. Shrock’s research is a giant step forward in understanding immune recognition, with important implications for viral immunoevasion and the design of immunosilent protein therapeutics.

As a postdoc in Dr. David Baker’s lab at the University of Washington, Shrock is taking a systematic approach to more broadly understand antibody recognition. She will execute a large-scale screen to characterize the antibody response against a diverse array of proteins. Shrock will then characterize the epitopes within these proteins and use her results to train an AI model to predict immunogenicity. In addition to providing fundamental learnings on immune recognition, Shrock’s findings will empower the design of future protein therapeutics that are invisible to our immune systems.

Bing Shui, Ph.D. Jane Coffin Childs Fellow

Massachusetts Institute of Technology

Project Title: Understanding tissue damage in the pre-neoplasia to neoplasia transition of colorectal cancer

Tissue regeneration, in a normal developmental context, and cancer are both forms of cellular proliferation. However, tissue regeneration is regulated and responsive to the surrounding environment, whereas cancer sheds these restraints. Understanding the commonalities and the differences between tissue regeneration and cancer may provide insight into novel avenues for cancer therapeutics.

Dr. Bing Shui will investigate the role of tissue damage in facilitating the early pre-neoplastic to neoplastic transition in colorectal cancer in Dr. Tyler Jacks’ lab at the Massachusetts Institute of Technology. Dr. Shui will examine how tissue damage cooperates with oncogenic mutations to initiate cancer. He will also compare damaged mutant and wildtype cells to identify vulnerabilities that can be leveraged to selectively destroy precancerous cells. Ultimately, a better understanding of the role of tissue damage in this early precancerous transition may reveal novel prophylactic cancer treatments.

Shui’s interest in the relationship between tissue regeneration and cancer burgeoned in Dr. Kevin Haigis’ lab at Harvard University. During his Ph.D. studies, he examined the role of microRNAs (miRNAs) in colon regeneration and colon cancer. First, Shui demonstrated that miRNAs are required for tissue regeneration and miRNA suppression exacerbated colon damage due to failed regeneration. Next, he examined the role of miRNAs in colon cancer and discovered a novel form of posttranslational regulation mediated by oncogenic K-Ras that governs global miRNA function. Now Shui will use his expertise in tissue damage and regeneration to identify vulnerabilities in colorectal cancer during his postdoctoral research.

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

National Institute of Health

Project Title: Phage and bacterial regulatory mechanisms

Howard A. Shuman, Ph.D. Jane Coffin Childs Fellow

Harvard University

Project Title: Maltose and maltodextrin transport in E. coli

Richard Shutt, Ph.D. Jane Coffin Childs Fellow

Stanford University

Project Title: Purification and characterization of mRNA coding for myeloma protein

Kausik Si, Ph.D. Jane Coffin Childs Fellow

Columbia University

Project Title: Molecular mechanism of synapse specific targeting of EF1-a and its role in synaptic growth

Matthew Sieber, Ph.D. Jane Coffin Childs Fellow

Carnegie Institution for Science

Project Title: Metabolic transitions during Drosophila oogenesis

Ruth B. Siegel, Ph.D. Jane Coffin Childs Fellow

University of Wisconsin, Madison

Project Title: The interaction of promoters and transcription factors

Vivian Siegel, Ph.D. Jane Coffin Childs Fellow

Max-Planck Institute /
University of California

Project Title: RNA localization in Drosophila development

Image of Miriam L. Siekevitz, Ph.D., J.D.

Miriam L. Siekevitz, Ph.D., J.D. Jane Coffin Childs Fellow

University of Cologne

Project Title: Idiotype regulation of the immune response

Ethan R. Signer, Ph.D. Jane Coffin Childs Fellow

Institut Pasteur

Project Title: Operon expression and lysogeny

Thomas J. Silhavy, Ph.D. Jane Coffin Childs Fellow

Harvard Medical School

Project Title: Periplasmic protein secretion in E. coli

Marion Silies, Ph.D. Jane Coffin Childs Fellow

Stanford University

Project Title: Neural integration of visual information in the Drosophila brain

My current research interest is visual system function in fruit flies. I want to understand how different behaviorally relevant visual cues, such as motion or polarized light information, are processed in the Drosophila brain.

I am from Germany. I studied biology and chemistry at the University of M√ºnster, where I worked in a plant pathology lab as an undergraduate; I also did internships at Washington State University and Edinburgh University. ¬†During that time I became interested in neuroscience and subsequently studied the development of the nervous system for my diploma thesis and PhD at the Department of Neurobiology in M√ºnster. I used the fly embryonic peripheral nervous system to study how neurons and glial cells communicate in order to coordinate axonal outgrowth with glial cell migration. For my postdoc I switched from developmental to functional aspects of neuroscience. Outside the lab, I enjoy exploring the Bay area on my road bike or hiking, and meeting friends.

Antonio Sillero, M.D., Ph.D. Jane Coffin Childs Fellow

New York University

Project Title: Protein synthesis in Artemia salina

Justin Silpe, Ph.D. HHMI-Jane Coffin Childs Fellow

Harvard University

Project Title: Dynamics and manipulation of the vaginal microbiome by bacteriophages

DNA-damaging agents are the pervasive inducers of temperate phages in model bacteria. Most bacteria in the biosphere are polylysogens, harboring multiple prophages. Thus, how co-residing prophages compete for cell resources if they all respond to an identical trigger is unknown. My project in the Bassler Lab is focused on the discovery of regulatory modules that control prophage induction independently of the DNA damage cue. The modules I uncovered lack sequence similarity but share regulatory logic by having a transcription factor that activates the expression of a neighboring gene encoding a small protein. The small protein inactivates the master repressor of lysis, leading to induction. Polylysogens harboring two prophages exposed to DNA damage release mixed populations of phages. Single-cell analyses reveal that this blend is a consequence of discrete subsets of cells producing one, the other, or both phages. By contrast, induction via the DNA-damage-independent module results in cells producing only the phage sensitive to that specific cue. Thus, in the polylysogens tested, the cue used to induce lysis determines phage productivity. Considering the lack of potent DNA-damaging agents in natural habitats, additional phage-encoded sensory pathways to lysis could play fundamental roles in phage-host biology and inter-prophage competition.

Allen E. Silverstone, Ph.D. Jane Coffin Childs Fellow

University of Edinburgh

Project Title: Biochemistry and genetic characterization of certain E. coli mutants

Daniel T. Simmons, Ph.D. Jane Coffin Childs Fellow

National Institutes of Health

Project Title: Translation of SV40 messenger RNA

Jeffrey A. Simon, Ph.D. Jane Coffin Childs Fellow

Harvard Medical School

Project Title: Trans-regulation by the Drosophila bithorax complex

Miljan Simonovic, Ph.D. Jane Coffin Childs Fellow

Yale University

Project Title: Structural study of co-translational translocation

Ila Singh, Ph.D. Jane Coffin Childs Fellow

University of California, San Francisco /
Stanford University

Project Title: A novel method for mutagenesis of a cloned gene

Harinder Singh, Ph.D. Jane Coffin Childs Fellow

Massachusetts Institute of Technology

Project Title: Mammalian transcriptional regulatory proteins and their genes

Niladri K. Sinha, Ph.D. Jane Coffin Childs - HHMI Fellow

Johns Hopkins University School of Medicine

Project Title: Defining mechanisms for selective translation in ribosomopathies

Translational elongation is a tightly regulated process, whose dysfunction triggers cellular quality control (QC) processes that minimize production of defective protein molecules. Aberrantly stalled ribosomes on messenger RNAs (mRNAs) disrupt translational homeostasis and arise as a consequence of inefficient decoding, defective mRNAs, and cellular insults, such as stress and starvation. As such, the primary role of co-translational QC is to initiate ribosomal rescue by splitting the ribosomal subunits, triggering mRNA decay, and enabling recycling of the subunits for new rounds of translation. _x000D_
The molecular cues required to initiate ribosomal QC (RQC) are poorly characterized, as are the fate of ribosomes affected by RQC. Using a combination of biochemical, mass-spectrometric and ribosome profiling approaches, I am studying how QC factors spatiotemporally recognize and resolve stalled ribosomes and how such factors discriminate terminally (or “dead end”) stalled ribosomes on defective mRNAs, from transiently paused ribosomes on elongation-limited transcripts. _x000D_

Ayesha Sitlani, Ph.D. Jane Coffin Childs Fellow

Yale University

Project Title: DNA bending by leucine-zipper proteins

Rufus E. Skillern, Ph.D. Jane Coffin Childs Fellow

University of California, Berkeley

Project Title: Factor controlling RNA chain initiation in lambda

Gary M. Skinner, Ph.D. Jane Coffin Childs Fellow

University of Arizona

Project Title: A single-molecule study of co-translational protein folding

Arthur I. Skoultchi, Ph.D. Jane Coffin Childs Fellow

Massachusetts Institute of Technology

Project Title: Mechanism of messenger RNA transport from the nucleus to the cytoplasm of the cleaving sea urchin embryo

Elenoe C. Smith, Ph.D. Jane Coffin Childs Fellow

Boston Children's Hospital

Project Title: DNA elements within BCL11A and its target sequences in globin switching

This project aims to identify cellular mechanisms contributing to elevation of fetal hemoglobin (HbF, ?2?2) levels, the most promising therapy for patients with sickle cell disease. The characterization of BCL11A, a repressor of HbF production, and potential BCL11A targets within the ?-globin locus, will impact therapy design and treatment of the major hemoglobin disorders whose global health burden is rising. Although BCL11A is dispensable for normal red cell function, studies in mice have determined that it is required for development, presenting a potential obstacle for therapies designed to inhibit BCL11A function by small molecule. Aim1 will determine the dependence of BCL11A erythroid expression on a single nucleotide polymorphism dense region, identified by genome wide association studies. Aim2 will identify a region required for ?-globin gene repression within the A?-? intergenic region of the ?-globin locus. Both aims will utilize DNA targeting of mouse embryonic stem cells and analysis of BCL11A expression and/or globin gene expression in fetal and adult mice. These studies will contribute to a fuller understanding of ?-globin gene regulation, provide in vivo models for molecular characterization of hemoglobin switching, and identify erythroid specific targets for therapeutic intervention.