Directory - Jane Coffin Childs Memorial Fund

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Pascal M. Devant, Ph.D. Jane Coffin Childs Fellow

Gladstone Institutes

Project Title: Engineering CAR T cells for Enhanced Cancer Immunotherapy via Protein Interaction Network Analysis

Cancer immunotherapies, such as chimeric antigen receptor (CAR) T cell therapies, have shown great promise against malignancies of the blood but have struggled to effectively treat solid tumors. During his fellowship, Dr. Pascal Devant will focus on understanding how T cells work in an effort to engineer CAR T cell therapies that can better attack solid cancers.

Devant developed his expertise in immunology during his graduate research in Dr. Jonathan Kagan’s lab at Harvard Medical School. There, he focused on caspases, key enzymes that work as the body’s early warning system of invaders. Devant discovered that inflammatory caspases are key enzymes in mammalian innate immunity, providing an alternative activation route to what was previously described. He structurally characterized a caspase complex, providing novel insights into substrate capture and processing.

Now, in Dr. Alex Marson’s lab at Gladstone Institutes, Dr. Devant will generate quantitative protein-protein interaction networks to identify key interactions that regulate T cell function. Devant will leverage this information, using gene editing and preclinical CAR T cell models, to engineer the next generation of CAR T cell therapies for the treatment of solid tumors. In addition to providing fundamental insight into how T cells work, Devant’s work holds great promise in clinical translation for cancer patients.

Daniel L. Dexter, Ph.D. Jane Coffin Childs Fellow

Institut Pasteur

Project Title: Differentiation in mammalian cell lines

Bryan C. Dickinson, Ph.D. Jane Coffin Childs Fellow

Harvard University

Project Title: Continuous directed evolution of proteases for cancer therapy

Dion K. Dickman, Ph.D. Jane Coffin Childs Fellow

University of California, San Francisco

Project Title: Genetic dissection of synaptic homeostasis

Rocky Diegmiller, Ph.D. Jane Coffin Childs Fellow

Duke University

Project Title: Dissecting the Dynamics of Tissue Patterning During Regeneration

Many animals, including zebrafish, have the ability to regenerate limbs, tails, or fins following amputation. The regeneration process is thought to faithfully reconstruct the appendage, yet it is unknown how spatial and temporal dynamics in gene expression and cell-signaling pathways control regrowth. Dr. Rocky Diegmiller will use quantitative imaging approaches to investigate morphological and patterning dynamics in regrowth of the paired zebrafish pectoral fin. Diegmiller will conduct these studies in Dr. Stefano Di Talia’s and Dr. Kenneth Poss’ labs at Duke University. Diegmiller will explore how gene expression patterns are re-formed following amputation, and throughout regeneration. These studies will reveal insights into the dynamics and robustness of regeneration, and will dissect how multiple signaling pathways are integrated to ensure faithful regeneration. Furthermore, these studies will generate quantitative tools for studying regeneration that can be applied to other systems.

As a graduate student, Diegmiller used mathematical models and imaging to investigate developmental biology in Dr. Stanislav Shvartsman’s lab at Princeton University. Specifically, Dr. Diegmiller used the Drosophila germline cyst as a model system to investigate cell polarity and the emergence of symmetry breaking mechanisms in cell clusters. With his multidisciplinary background in developmental biology, Dr. Diegmiller hopes his research will also yield important connections and distinctions between developmental and regenerative pathways.

Frances F. Diehl, Ph.D. HHMI-Jane Coffin Childs Fellow

Johns Hopkins University

Project Title: Deﬁning regulatory principles of translation during nutrient shifts

Protein synthesis is metabolically costly; it is therefore critical that cells regulate translation based on nutrient availability. Translation regulation must be flexible to enable cells to adapt to persistent nutrient deprivation, but still recover when nutrients are replenished. Signaling through the kinases GCN2 and mTORC1 can suppress both translation initiation and elongation in response to nutrient depletion, but how each mechanism contributes to global translational control is unclear. Here we investigate translation dynamics upon acute and long-term nutrient depletion, as well as during recovery from nutrient stress. In the immediate response to starvation, GCN2 robustly inhibits initiation to prevent ribosome loading onto transcripts. However, over longer periods of starvation, increased initiation causes translating ribosomes to collide with ribosomes stalled on transcripts. To explore these different temporal regimes, we employ a mass spectrometry-based approach to identify factors that modulate ribosome activity in response to nutrient stress through differential ribosome binding. This work will provide a more integrated understanding of how cells regulate translation and ribosome homeostasis across nutrient environments.

Daniel C. DiMaio, M.D., Ph.D. Jane Coffin Childs Fellow

Harvard University

Project Title: In vitro mutagenesis of cloned globin genes

Randall L. Dimond, Ph.D. Jane Coffin Childs Fellow

Massachusetts Institute of Technology

Project Title: Gene Expression

Lori A. Dodson, Ph.D. Jane Coffin Childs Fellow

Massachusetts Institute of Technology

Project Title: DNA damage into mutations

John G. Doench, Ph.D. Merck-Jane Coffin Childs Fellow

Harvard Medical School

Project Title: Synthetic lethal interactions in cancer

Caroline A. Doherty, Ph.D. Jane Coffin Childs Fellow

University of California, San Francisco

Project Title: Ovulation of the ﬁttest

Mammals with ovaries are born with a non-renewing supply of differentiated oocytes ranging from the thousands in mice to the millions in humans. While these high numbers imply a large stockpile, only a comparatively small number of the oocytes present at birth will ever be successfully ovulated and fertilized. To achieve this maturation, an oocyte must first be activated from its quiescent state and then undergo a period of extensive growth in order to accumulate large quantities of biosynthetic materials that are necessary to support the embryo prior to zygotic genome activation. We are currently limited in our understanding of factors that determine whether an oocyte will complete this growth or be fated for elimination/atresia. My research focuses on how both the intrinsic characteristics of oocytes and the extrinsic support provided by the surrounding somatic tissue determine whether an oocyte present at birth will ever be successfully ovulated. My goal is to apply this knowledge to future therapeutics for infertility.

Henrik G. Dohlman, Ph.D. Jane Coffin Childs Fellow

University of California, Berkeley

Project Title: Mechanisms of desensitization to the pheromone response in yeast

Thomas F. Donahue, Ph.D. Jane Coffin Childs Fellow

Cornell University

Project Title: Transposition of genetic elements in eukaryotes

Rui Dong, Ph.D. Jane Coffin Childs Fellow

University of California, San Francisco

Project Title: Probe the interplay between actin cytoskeleton and immunoreceptor signaling

Immune responses rely on T cell receptors (TCRs) activating robustly upon binding foreign-antigens, but staying quiescent with abundant self-antigens. How TCRs convert small differences of extracellular interactions into binary intracellular signals remains elusive. Actin is a key regulator in controlling receptor dynamics, transport and clustering. However, little is known about how actin is coupled to TCRs and influences T cell signaling. I propose to dissect the cellular mechanisms that regulate receptor dynamics, particularly focusing on the crosstalk between receptors and actin. I hypothesize that receptor clustering is required for actin coupling, and that actin coupling exerts forces on receptors that facilitate ligand proofreading. This hypothesis will be tested by: (1) Determine how the spatial organization of the TCR affects its coupling to actin, by manipulating nanoscale receptor organization using DNA origami. (2) Define the contribution of force-generating actin network in ligand discrimination by single-molecule measurements of receptor-ligand kinetics. (3) Identify the molecular linkage between actin and TCRs, by proteomic profiling of TCR proximity interactome dependent of intact actin network. The proposal constitutes the first mechanistic study of how actin interacts with TCRs and impacts signaling and ligand discrimination. The results could provide new insights into new strategies for cell immunotherapy.

Tabitha Doniach, M.D., Ph.D. Jane Coffin Childs Fellow

University of California, Berkeley

Project Title: Dorsal axis formation in Xenopus laevis

Seth Donoughe, Ph.D. Jane Coffin Childs Fellow

University of Chicago

Project Title: Dissecting mechanical feedback in the Drosophila egg chamber

Gian Dotto, M.D., Ph.D. Jane Coffin Childs Fellow

Whitehead Institute

Project Title: Initiation-promotion in carcinogenesis

Martin Douglass, Ph.D. Jane Coffin Childs Fellow

Vanderbilt University

Project Title: Defining how Clostridioides difficile engages in microbial warfare

Clostridioides difficile infection (CDI) is the leading cause of hospital-acquired and antibiotic-associated intestinal infections. However, we do not currently have a clear understanding of CDI pathogenesis, which impedes the development of additional therapeutic strategies. Dr. Martin Douglass will investigate how CDI overcomes the human microbiota and immune system in Dr. Eric Skaar’s lab at Vanderbilt University Medical Center. Dr. Douglass will examine how CDI competes for nutrients with the microbiota and immune system. Furthermore, Dr. Douglass will identify which CD genes are required for host colonization and persistence. These studies may provide insight into novel therapeutic targets for treating CDI.

As a graduate student in Dr. M. Stephen Trent’s lab at the University of Georgia, Douglass examined the outer membrane of Gram-negative bacteria. Dr. Douglass discovered novel proteins that are required for the transport of lipids to the outer membrane. These studies provide potential therapeutic targets for novel antibiotics and provide Douglass with a solid foundation for interrogating new targets in CDI.

Jeffrey B. Doyon, M.D., Ph.D. Jane Coffin Childs Fellow

University of California, Berkeley

Project Title: Investigation of dynamin's role in the temporal regulation of actin remodeling during endocytic vesicle formation

Gabriel R. Drapeau, Ph.D. Jane Coffin Childs Fellow

Stanford University

Project Title: Protein structure and function

Ines A . Drinnenberg, Ph.D. Jane Coffin Childs Fellow

Fred Hutchinson Cancer Center

Project Title: Causes and consequences of a non-canonical H2A variant in flies

My research focuses on the evolutionary diversity of centromeric architectures. Faithful chromosome segregation in all eukaryotes relies on centromeres, the chromosomal sites that recruit the kinetochore protein complex to mediate spindle attachment during cell division. Yet, despite this essential function centromeres are remarkably diverse. Most chromosomes are monocentric i.e., kinetochore assembly is restricted to a defined chromosomal region. In contrast, holocentromeres have kinetochores attached along the entire length of chromosomes. Holocentric chromosomes have evolved multiple times independently from monocentric ancestors. Yet, despite their dramatically different centromeric architectures, the transition to holocentric chromosomes has remained enigmatic.

I performed a computational survey for centromere and kinetochore components in mono- and holocentric insect orders. This study revealed the unexpected finding that the centromere specific histone variant, CenH3 ¬ñ known to be essential for centromere function in most eukaryotes ¬ñ was lost on all four lineages that are associated with independent transitions from mono- to holocentric chromosomes. Expanding my analyses to other kinetochore components I found that homologs of many inner kinetochore proteins are still present, suggesting that holocentric insects utilize alternative ways of initiating kinetochore assembly on chromatin. Currently I am in the process of determining the CenH3-independent kinetochore assembly pathway as well as the molecular architecture of the insect holocentromere.

Robert Driscoll, Ph.D. Jane Coffin Childs Fellow

Stanford University

Project Title: Molecular dissection of the replication checkpoint

My current research involves analysis of the cellular response to replication fork stress.

After finishing my undergraduate degree at the University of Leeds in the UK, still pretty clueless as to what I wanted to study, I worked in the lab of E. Peter Geiduschek at the University of California, San Diego, as a research technician. There, I developed a fascination with DNA metabolism. I continued pursing this interest ¬†by studying DNA repair in the lab of Steve Jackson at Cambridge University for my doctoral studies, and am now studying DNA replication. I greatly enjoy the challenge of independent academic research but also the fact that it is a very social endeavor. When I’m not in the lab, I’m usually hiking and camping in California or enjoying its excellent food and beverages.

Michelle L. DuBois, Ph.D. Jane Coffin Childs Fellow

Fred Hutchinson Cancer Center

Project Title: In vivo analysis of silent chromatin domains

Mark E. Dudley, Ph.D. Jane Coffin Childs Fellow

University of Pennsylvania

Project Title: Expression of the heterochronic Tp2 locus of maize

Erastus C. Dudley, Ph.D. Jane Coffin Childs Fellow

National Institutes of Health

Project Title: Transcriptional control of helper T-cell development

Elizabeth S. Dugan, Ph.D. Jane Coffin Childs Fellow

Johns Hopkins University /
University of Michigan

Project Title: Hapten specific tolerance

Leonard R. Duncan, Ph.D. Jane Coffin Childs Fellow

Washington University in St. Louis

Project Title: Control of reproductive cell fate in Volvox carteri

Rebecca K. Dunn, Ph.D. Jane Coffin Childs Fellow

Massachusetts General Hospital

Project Title: Function of histone ubiquitination in chromatin regulation

Alex R. Dunn, Ph.D. Jane Coffin Childs Fellow

Stanford University

Project Title: Determining the mechanism of myosin V processivity

Wesley A. Dunnick, Ph.D. Jane Coffin Childs Fellow

Medical Research Council (MRC),UKRI

Project Title: Immunoglobulin mRNA

Michael L. Dustin, Ph.D. Jane Coffin Childs Fellow

Washington University in St. Louis

Project Title: Expression cloning of I-cell disease enzyme

Vinay Eapen, Ph.D. Jane Coffin Childs Fellow

Harvard Medical School

Project Title: Systemic analysis of the mammalian selective autophagy cargo network

The 2016 Nobel laureate Dr. Yoshinori Ohsumi remarked, “ Life is an equilibrium state between the synthesis and degradation of proteins”. My research focuses on Autophagy, a process whereby proteins are marked for destruction in cells by the lysosome. I became interested in autophagy during my PhD in Dr. Jim Haber’s lab at Brandeis University, and have been hooked on it ever since!_x000D_
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The autophagy-lysosome system targets the degradation of a specific cohort of proteins via “selective autophagy”. The dysfunction of this phenomenon has been linked to a myriad of human disorders. We have only scratched the surface of the known targets of this fascinating biological process. Under the guidance of my mentors, the aim of my research will be to comprehensively catalog the list of selective autophagy substrates by employing quantitative mass spectrometry of the autophagy-lysosome system. An overarching goal of my research is to obtain knowledge of the selective autophagic targets in cancer, which may present opportunities for the specific targeting of this process_x000D_
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I grew up in New Delhi, India. After completing my undergrad program in Biotechnology at the Vellore Institute of Technology in South India, I moved to the U.S. (Brandeis university, MA) for graduate studies. In my spare time, I am whittling down all of the 48 four thousand feet peaks in the White Mountain range while assiduously taking guitar lessons in the hope of one day playing lead guitar for a major rock band.

Suzanne Eaton, Ph.D. Jane Coffin Childs Fellow

University of California, San Francisco

Project Title: Study a screen for genes regulating developmental compartments

Aline Eden, Ph.D. Jane Coffin Childs Fellow

Rockefeller University

Project Title: Isolation of complement receptors from lymphoid cells

Arthur S. Edison, Ph.D. Jane Coffin Childs Fellow

University of Wisconsin, Madison

Project Title: NMR studies of the neurobiology of Ascaris suum

John Barry Egan, Ph.D. Jane Coffin Childs Fellow

Stanford University

Project Title: Basic genetic control mechanisms

Thomas T. Egelhoff, Ph.D. Jane Coffin Childs Fellow

Massachusetts Institute of Technology

Project Title: Biochemical and genetic investigation of yeast myosin

Edward H. Egelman, Ph.D. Jane Coffin Childs Fellow

Medical Research Council (MRC),UKRI

Project Title: Higher resolution structure of F-actin

Gudmundur Eggertsson, Ph.D. Jane Coffin Childs Fellow

International Laboratory of Genetics and Biophysics (IGB-CNR)

Project Title: Mechanisms of suppressor mutations (suppressors) in E. coli, employing both biochemical and genetic methods of analysis

Melanie Ehrlich, Ph.D. Jane Coffin Childs Fellow

Albert Einstein College of Medicine

Project Title: Physical properties of yeast mitochondrial DNA

Duane C. Eichler, Ph.D. Jane Coffin Childs Fellow

Stanford University

Project Title: E coli restriction enzyme

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

Massachusetts Institute of Technology

Project Title: Regulatory elements of yeast CYC1 transcription

Robert T. Elder, Ph.D. Jane Coffin Childs Fellow

Stanford University

Project Title: Structure of Tyl RNA

Sarah CR. Elgin, Ph.D. Jane Coffin Childs Fellow

California Institute of Technology

Project Title: Non-histone chromosomal proteins

Andrew EH. Elia, M.D., Ph.D. HHMI-Jane Coffin Childs Fellow

Brigham and Women's Hospital

Project Title: Harnessing lysine acetylation and methylation in the DNA damage response

Leah J. Elias, Ph.D. Jane Coffin Childs Fellow

Johns Hopkins University School of Medicine

Project Title: Using single cell transcriptomics to understand homeostatic sleep pressure

Sleep disorders are common and negatively impact our quality of life and biological health. Yet, how the brain encodes the need for restorative sleep is poorly understood. Dr. Leah Elias will investigate the cellular circuits and molecular signals that encode sleep pressure in Dr. Seth Blackshaw’s lab at Johns Hopkins University School of Medicine. Using single nucleus RNA sequencing, Dr. Elias has identified a cluster of neurons that are activated by sleep deprivation. Furthermore, she has identified candidate genes that are differentially regulated in response to sleep deprivation. She will leverage these findings to mechanistically dissect sleep signals in the brain at the cellular and molecular levels. Dr. Elias’ research has important implications for the basic biology of sleep and may reveal novel therapeutic targets for sleep and metabolic disorders.

As a PhD student in Dr. Ishmail Abdus-Saboor‘s lab at the University of Pennsylvania, Dr. Elias studied the neural circuitry controlling social touch. Specifically, she identified a new pathway that connects social touch in the skin to reward circuits in the brain. With this background in neural circuitry, Dr. Elias will now investigate how the need for sleep is encoded in the brain.

Laura AB. Elias Barker, Ph.D. Jane Coffin Childs Fellow

Stanford University

Project Title: ATP-dependent chromatin remodeling in dendritic morphogenesis and targeting

My work in Gerald Crabtree¬ís laboratory focuses on elucidating how structural changes in the packaging of DNA, otherwise known as chromatin, contributes to the acquisition of cellular identity. Specifically, I am investigating the mechanism by which subunit switches in an ATP-dependent chromatin remodeling complex promote the development and maturation of neural progenitor cells into fully functional neurons.

I have been driven throughout my training by a passion for discovery and appreciation for a scientific, analytical approach to problem-solving. I majored in biology at Swarthmore College and earned my PhD in the Neuroscience Program at the University of California, San Francisco (UCSF). My thesis in Arnold Kriegstein¬ís laboratory at the UCSF Institute for Regeneration Medicine focused on elucidating the mechanism by which newborn neurons migrate from their places of origin to specific cortical regions, where they integrate into the brain¬ís circuitry. ¬†During my postdoctoral fellowship, I have expanded my studies to include genomics, proteomics and biochemistry to probe the role chromatin structure plays during neural development. ¬†¬†I aspire to use my training to have a broad impact on the global scientific community, and influence the incorporation of scientific innovation into society.

Ronald E. Ellis, Ph.D. Jane Coffin Childs Fellow

University of Wisconsin, Madison

Project Title: Analysis of the gene fog-1 of C. elegans

Joanne Engebrecht, Ph.D. Jane Coffin Childs Fellow

Yale University

Project Title: Role of RED1 in meiotic chromosome segregation

Suzanne L. Epstein, Ph.D. Jane Coffin Childs Fellow

National Cancer Institute

Project Title: Characterization of Ia antigens

Priscilla A. Erickson, Ph.D. Jane Coffin Childs Fellow

University of Virginia

Project Title: Genetics and evolution of photoperiodism in Drosophila melanogaster

Organisms exhibit diverse strategies to survive environments that vary in space and time. In temperate climates, environmental cues are used to anticipate the onset of unfavorable seasons. One of the most reliable indicators of season is photoperiod: the length of light and dark periods within a 24-hour day. Insects exhibit a spectacular array of responses to changes in season. For example, aphids develop sexually reproducing morphs in the fall, moths and lacewings develop unique seasonal patterns and colors, monarch butterflies undergo seasonal migrations, and hundreds of species, including the fruit fly Drosophila melanogaster, are able to suspend development or reproduction until more favorable conditions return. Despite nearly a century of research on insect seasonality and photoperiodism, the genetic pathways used to make these ecologically crucial transitions remain unknown. The abundance of genetic and genomic resources for Drosophila makes it an ideal study system for this question._x000D_
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My research uses custom-built environmental chambers, field studies in an experimental orchard, and novel genetic mapping techniques to dissect the genetic basis of photoperiodism and seasonal responses in Drosophila. Understanding how insects detect photoperiod will inform our understanding of economically and biomedically important insects and offer predictions about how insects may adapt to ongoing anthropogenic climate warming in which temperature, but not photoperiod, is changing.