Directory - Jane Coffin Childs Memorial Fund

Status

Year Appointed

Institution

Name

Clear Filters

Thomas F. Cooke, Ph.D. Jane Coffin Childs - HHMI Fellow

Whitehead Institute

Project Title: The origin and evolution of cell types

One of the special features of animal and plant cells is their differentiation into hundreds of specialized types. How these diverse cells originated is a fundamental question in evolution. To approach this question, I am using single-cell RNA sequencing to characterize hundreds of cell types across diverse species of planarians and their distant relatives. This will enable a search for key regulatory factors in an unprecedented range of differentiation pathways, guided by the fact that conserved expression is a common feature of such genes. Planarians are particularly well-suited for testing the function of fate-specifying genes because cell differentiation is an ongoing process in all tissues in the adult stage, and during regeneration. Through this approach, I propose to learn general principles concerning the molecular basis of cell type homology across diverse animal taxa._x000D_
_x000D_

Geoffrey M. Cooper, Ph.D. Jane Coffin Childs Fellow

University of Wisconsin, Madison

Project Title: RNA tumor virus DNA

Douglas NW. Cooper, Ph.D. Jane Coffin Childs Fellow

Whitehead Institute

Project Title: Identification and characterization of receptors in the endoplasmic reticulum

Gregory M. Cooper, Ph.D. Jane Coffin Childs - Merck Fellow

University of Washington

Project Title: Stratifying genomic variation to increase power in genetic association studies of common human diseases

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

Stanford University

Project Title: Analysis of centrosome duplication in human cells

Jacob Corn, Ph.D. Jane Coffin Childs Fellow

University of Washington

Project Title: Computational design of eukaryotic signal transduction

David K. Cortez, Ph.D. Jane Coffin Childs Fellow

Baylor College of Medicine

Project Title: Identification and analysis of APC substrates

Maria C. Costanzo, Ph.D. Jane Coffin Childs Fellow

Cornell University

Project Title: Gene expression

Thomas Cotner, M.D., Ph.D. Jane Coffin Childs Fellow

Dana-Farber Cancer Institute

Project Title: Structure of human thymus-leukemia-like antigens

Joseph A . Cotruvo, Ph.D. Jane Coffin Childs Fellow

University of California, Berkeley

Project Title: Intersection of nitric oxide- and copper-mediated signaling pathways in mammalian cells

Nitric oxide (NO) is a ubiquitous gasotransmitter involved in vasorelaxation, neurodegeneration, apoptosis, and other processes, and linked to numerous pathologies, including cancer. A major mechanism of NO signaling is S-nitrosation, the oxidative modification of cysteine residues, but how this occurs in vivo is poorly understood. Copper ions catalyze Snitrosation in vitro, while recent data point to mobile pools of copper playing unknown roles in signaling pathways. This proposal aims to connect copper- and NO-mediated signaling, using the lipolysis pathway of adipocytes as a model system. Our preliminary data suggest copper and NO modulate the activity of phosphodiesterase (PDE) 3B. We propose that copper, bound to a protein or small molecule, catalyzes S-nitrosation of PDE3B, inhibiting the enzyme. We will test this hypothesis by altering cellular copper and NO levels via gene knockdowns, and assaying PDE3B activity in extracts. We will detect differences in PDE3B S-nitrosation under these conditions and determine the cysteine(s) modified. Finally, we will search for endogenous copper ligands and reconstitute the S-nitrosation system in vitro. These studies will yield insights into NO’s physiology, unravel a novel signaling role of copper, and motivate examination of copper signaling in other mammalian cell types.

Ya'el Courtney, Ph.D. Jane Coffin Childs Fellow

Stanford University

Project Title: Deciphering the Role of EBV-Infected B Cells and Autoimmunity in Post-Infectious Syndromes and Developing a Targeted Elimination Strategy

Illness can interfere with the brain’s ability to function properly, affecting much more than just clear thinking. Dr. Ya’el Courtney’s fellowship research is uncovering how immune responses to illness contribute to neurological dysfunction and may even trigger neurodegenerative processes, revealing new connections between the immune system and the brain.

During her thesis research in Dr. Maria Lehtinen’s lab at Harvard University, Courtney revealed how the choroid plexus, a specialized brain structure that produces cerebrospinal fluid is regulated. She found that secreted factors stimulate the development of specialized neural cells and alter their developmental trajectory. Interestingly, environmental factors such as maternal exposure to certain drugs or immune activation in response to illness also trigger secretion of factors and, eventually, can influence offspring behavior.

Dr. Courtney will examine immune-neurological interplay in Dr. William Robinson’s lab at Stanford University in a different context. There, she’ll examine how autoimmune responses in chronic post-infectious syndromes, such as post-treatment Lyme disease or long COVID, drive neurological manifestations. Courtney’s research has the potential to uncover novel immune-neurological connections and may elucidate novel and therapeutically tractable targets for patients with these long-lasting post-infection syndromes.

Peter A. Covitz, Ph.D. Jane Coffin Childs Fellow

Stanford University

Project Title: Cell proliferation in legume nodulation

Jeffery S. Cox, Ph.D. Jane Coffin Childs Fellow

Albert Einstein College of Medicine

Project Title: Identification of genes involved in mycobacterial virulence

Daniel N. Cox, Ph.D. Jane Coffin Childs Fellow

University of California, San Francisco

Project Title: Molecular mechanisms of dendritic morphogenesis

George N. Cox, Ph.D., J.D. Jane Coffin Childs Fellow

University of Colorado, Boulder

Project Title: Molecular genetic studies of nematode collagen genes

Jean Crabbé, M.D. Jane Coffin Childs Fellow

Brigham and Women's Hospital

Project Title: Relationship of adrenal hormones to hypertension and cancer

Susan W. Craig, Ph.D. Jane Coffin Childs Fellow

Johns Hopkins University

Project Title: Cholera toxin receptors on rat lymphocyte membranes

John D. Crispino, Ph.D., MBA Jane Coffin Childs Fellow

Children's Hospital, Boston

Project Title: The role of GATA-1 in hematopoiesis

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

University of California, Los Angeles

Project Title: Mitochondrial oxidative phosphorylation

Andrea Cuentas-Condori, Ph.D. Jane Coffin Childs Fellow

Yale University

Project Title: Synapse organization and circuit function of dual-transmitter neurons

A single neuron can use more than one neurotransmitter to signal with neighboring cells and regulate, for example, movement, reward and vision in mammalian systems. These dual-transmitter neurons can segregate molecularly distinct presynaptic terminals within a single axon and each neurotransmitter can regulate an independent or complementary role within a functional circuit. Although dual-transmitter neurons are conserved in vertebrates and invertebrates, very little is known about what diﬀerentially regulates neurotransmitter-speciﬁc synaptic pools and how this intracellular speciﬁcity shapes circuit function. Here, I propose to establish in vivo models of dual-transmitter neurons and use the well-mapped nervous system of the nematode Caenorhabditis elegans to understand how molecularly distinct synapses organize and segregate within a single neuron to regulate animal behavior. I will focus on the motor neuron SMD, the interneuron RIB and the neurosecretory NSM neuron to establish in vivo paradigms of dual-transmission with trackable behavioral consequences. My goal is to carry out a genetic screen to identify genes that organize neurotransmitter-speciﬁc synapses and track the functional consequences of ablating one subset of synapses. This proposal could reveal conserved cell biological programs of intracellular synapse placement in dual-transmitter neurons and link them with circuit function in a living organism.

Michael R. Culbertson, Ph.D. Jane Coffin Childs Fellow

Cornell University

Project Title: Cell regulation in eucaryotes

Paul M. Cullis, Ph.D. Jane Coffin Childs Fellow

University of North Carolina, Chapel Hill

Project Title: Synthesis of potent enzyme inhibitors

Valerie D. Daggett, Ph.D. Jane Coffin Childs Fellow

Stanford University

Project Title: Molecular modelling of protein folding

Lei Dai, Ph.D. Jane Coffin Childs - HHMI Fellow

University of California, Los Angeles

Project Title: Forecasting evolution of drug resistance in hepatitis C virus

I am broadly interested in the evolution of drug resistance. For example, how does the distribution of fitness effects influence the predictability of evolution? What is the role of epistasis in the adaptation to higher drug resistance? How can we integrate in vitro fitness data with in vivo models to design personalized drug therapy for patients?_x000D_
_x000D_
To address these questions, I combine high-throughput in vitro fitness measurements with mathematical models of viral dynamics to predict the evolution of drug resistance in Hepatitis C Virus and HIV. Using deep sequencing, I perform high-throughput fitness assays for a library of mutant viruses to systematically explore epistasis and evolutionary pathways towards drug resistance. By combining empirical fitness landscapes with mathematical models of within-host viral dynamics and pharmacokinetics/pharmacodynamics, I build a quantitative framework to predict viral evolution and minimize the risk of drug resistance during therapy. The principles for rational design of antiviral therapy will inform patient-specific therapy of targeted cancer drugs.

Eric Dang, Ph.D. Jane Coffin Childs - Merck Fellow

University of California, San Francisco

Project Title: Uncovering the molecular drivers of lethal invasive fungal infection

Hai Dao, Ph.D. Jane Coffin Childs Fellow

Princeton University

Project Title: Defining the interactome of the acidic patch with chromatin effectors

Recent studies have revealed the nucleosome acidic patch as a nexus for chromatin interacting proteins. Understanding the regulation underlying these binding events is critical to understanding of how genetic material is packaged and accessed in eukaryotes and how misregulation can lead to disease. It is well established that post-translational modifications (PTMs) of the histone tails help choreograph biochemical outputs on chromatin. By contrast, much less is known about how PTMs regulate access to the acidic patch, even though several modifications are proximal to this region. My research will combine the specificity of diazirine-based photocrosslinking reaction with high-throughput mass spectrometry-based techniques to accelerate the investigations into these regulations. The applications will be showcased in ascertaining the binding site between chromatin-remodeling proteins and the acidic patch, and a large-scale study to define the interactome of the acidic patch and chromatin effectors as the function of PTMs.

Alicia Darnell, Ph.D. Jane Coffin Childs - Merck Fellow

Massachusetts Institute of Technology

Project Title: Understanding cellular and organismal amino acid homeostasis

Robert A. Darrow, Ph.D. Jane Coffin Childs Fellow

Medical Research Council, MRC

Project Title: Isolation of variant B. subilis

Rhiju Das, Ph.D. Jane Coffin Childs Fellow

University of Washington

Project Title: Prediction of novel protein folds at high resolution

Robert C. Davenport, Ph.D. Jane Coffin Childs Fellow

Massachusetts Institute of Technology

Project Title: X-ray crystallographic studies on protein-DNA interactions

Yunji Wu. Davenport, Ph.D. Jane Coffin Childs - Simons Foundation Fellow

Harvard Medical School

Project Title: Molecular messages in algal-bacterial symbiosis

Ronald G. Davidson , M.D. Jane Coffin Childs Fellow

University of London, Kings College

Project Title: Biochemical Genetics

Bryan W. Davies, Ph.D. Jane Coffin Childs Fellow

Harvard Medical School

Project Title: Mapping virulence regulatory and signaling networks in vibrio cholera

I am mapping regulatory and signaling networks in Vibrio cholerae to identify factors and pathways that are required for virulence.

Improving the health of our world is a complex problem. ¬†The balancing act between providing food and health care for the masses, protecting the environment, ¬†and improving economies in developed and developing nations is often difficult. ¬†I enjoy science because of the unlimited potential it offers to provide solutions to many of the problems inherent in creating this balance. The basic sciences provide answers to the inner workings of life. ¬†These insights offer the possibility of developing new products to improve health care, decrease our environmental impact and improve food production, while simultaneously fostering the growth of new industries to bring products to those who need them. ¬†And it can all start at the laboratory bench just by asking, why?””

Joseph H. Davis, Ph.D. Jane Coffin Childs Fellow

Scripps Research Institute

Project Title: Evolutionary profile of ribosome biogenesis

Barry L. Davison, Ph.D., J.D. Jane Coffin Childs Fellow

Centre national de la recherche scientifique (CNRS)

Project Title: Gene expression in yeast

Theodore K. Dayie, Ph.D. Jane Coffin Childs Fellow

Massachusetts Institute of Technology /
Scripps Research Institute

Project Title: Structure and dynamics of an rRna-protein complex by NMR

Jon K. De Riel, Ph.D. Jane Coffin Childs Fellow

Yale University

Project Title: Molecular genetics of human hemoglobin synthesis

Image of Edward M. De Robertis, M.D., Ph.D.

Edward M. De Robertis, M.D., Ph.D. Jane Coffin Childs Fellow

Medical Research Council (MRC),UKRI

Project Title: Regulation of gene expression

Russell A. DeBose-Boyd, Ph.D. Jane Coffin Childs Fellow

University of Texas Southwestern

Project Title: Site-2 protease for SREBPs: biochemical characterization

Katherine A. Deets, Ph.D. HHMI - Jane Coffin Childs Fellow

University of Utah

Project Title: Evolutionary immunology in Tetrahymena

A wide range of organisms – such as nematodes, sea anemones, and bacteria – possess immune defenses to protect themselves against infectious microbes and viruses. Yet studying the interactions between hosts and infectious microbes remains limited to a handful of species. Dr. Katherine Deets will expand this list by examining the interactions between Tetrahymena thermophila and viruses in Dr. Nels Elde’s lab at the University of Utah. Dr. Deets is currently identifying novel viruses that infect Tetrahymena, and working to understand how Tetrahymena defend themselves against these viruses. This research will unlock a new experimental platform with powerful genetic tools for diversifying studies of the evolution of host-virus interactions.

As a graduate student, Deets investigated host-microbe interactions in the context of the mouse small intestine in Dr. Russell Vance’s lab at the University of California, Berkeley. Dr. Deets discovered a novel mode of antigen presentation that only occurs following inflammasome activation. This finding revealed a new connection between innate and adaptive immunity in the intestine. Dr. Deets will use her experience in host-microbe interactions to expand our understanding of immune defense in diverse.

Richard W. Deibler, Ph.D. Jane Coffin Childs Fellow

Harvard Medical School

Project Title: A systems biology analysis of the DNA damage response

Sebastian Deindl, Ph.D. Jane Coffin Childs Fellow

Harvard University

Project Title: Mechanistic studies of ATP-dependent chromatin remodeling enzymes

Current research: With a combination of novel single-molecule imaging approaches and traditional biochemical techniques I am investigating the mechanisms of ATP-dependent chromatin remodelers, a class of enzymes that dynamically alter chromatin structure.

I am intrigued by the notion that virtually all chemical reactions in our bodies are carried out by microscopic yet intricate molecular machines. For this reason, I decided to study the workings of these machines at a molecular level. John Kuriyan’s laboratory at the University of California, Berkeley was the perfect place for this work. There I studied the allosteric control of protein kinases and developed a passion for correlating protein structure with function. For my postdoctoral research I decided to venture into another important area of biology and study dynamic aspects of chromatin remodeling enzyme mechanisms using single-molecule imaging techniques in Xiaowei Zhuang’s laboratory at Harvard. Next to doing science, I enjoy windsurfing and surfing.

Luigi Del Gatto, M.D. Jane Coffin Childs Fellow

University of California, Berkeley

Project Title: Human serum lipoproteins

Benjamin Delatte , Ph.D. Jane Coffin Childs - HHMI Fellow

La Jolla Institute for Immunology

Project Title: TET loss-of-function and R-loops-mediated genomic instability in cancer

The TETs (TET1, TET2, TET3) are epigenetic enzymes regarded as responsible for active and passive DNA demethylation, and are involved in a wide array of physiological and pathological cellular responses.

I have performed my Ph.D training in Prof. François Fuks’ laboratory in Belgium at the time that TET function was discovered by the team of Prof. Anjana Rao. Applying proteome and genome-wide approaches, we found that the most potent partner of TETs is the glycosyltransferase OGT (Deplus*, Delatte* et al., Embo, 2013), and I recently discovered that Tet is responsible for RNA hydroxymethylation in drosophila (Delatte et al., Science, 2016).

Therefore, I naturally couldn’t resist joining Anjana’s lab where I am now investigating the roles of TETs and hydroxymethylcytosine in genomic instability and cancer. I am also fascinated by the advances in next-generation sequencing, and am developing novel methodologies to map epigenetic modifications, but also identify diverse hallmarks of cancer such as DNA breaks or aberrant DNA:RNA structures.

Outside of the lab, I enjoy surfing, hiking, and particularly love watching movies with friends.

benche65@gmail.com

Kristen E. DeMeester, Ph.D. Jane Coffin Childs Fellow

Scripps Research Institute

Project Title: Chemoproteomic discovery of small-molecule probes for autophagy proteins

Marlis K. Denk-Lobnig, Ph.D. Jane Coffin Childs Fellow

University of Michigan

Project Title: Understanding how bacteria-bacteria interactions influence antibiotic resistance in a microbiome context

Cells and organisms such as bacteria or cancer cells live in communities and have complex population-level dynamics and emergent behaviors. These behaviors can significantly change their collective properties, including resistance to drugs and other environmental selective pressures. Predicting how cellular communities, rather than individuals, respond to drug exposure could help delay or prevent drug resistance during treatment.

Spatial structure and heterogeneity are important features of such communities – from the cell to the ecosystem scale. In my research, I aim to understand the essential, but poorly understood, relationship between spatial structure and population-level dynamics in bacterial biofilm communities responding to antibiotic selection via theoretical and experimental approaches.