Directory - Jane Coffin Childs Memorial Fund

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David P. Toczyski, Ph.D. Jane Coffin Childs Fellow

University of Washington

Project Title: Mating partner selection in yeast

Joanne Topol, Ph.D. Jane Coffin Childs Fellow

California Institute of Technology

Project Title: RNA and protein localization in the Drosophila egg

Margaret E. Torrence, Ph.D. Jane Coffin Childs Fellow

Massachusetts Institute of Technology

Project Title: Defining the role of tertiary lymphoid structures in pancreatic cancer

Pancreatic cancer represents 3% of all new cancer cases in the United States, yet it has the worst 5-year survival rate of all cancer types. While many cancer types display durable responses to cancer immunotherapy, which harnesses the cytotoxic activity of the immune system to treat malignancies, immunotherapy has largely failed to treat pancreatic ductal adenocarcinoma (PDAC). The complex tumor microenvironment of PDAC likely underlies the refractory response of PDAC to immunotherapy, including immune checkpoint blockade (ICB). One example of a known mechanism that aids immune evasion by PDAC is the presence of desmoplastic stroma that hinders the infiltration of cytotoxic T cells. In addition to exclusion of immune infiltrate, the cytotoxic T cells that are present within the microenvironment are dysfunctional. Nutrient availability within the tumor environment likely impacts the function of cytotoxic T cells and research in immunometabolism is of growing interest. Understanding cell-specific metabolic changes within GEMMs has been hindered by a lack of mouse models that properly recapitulate the tumor microenvironment and lack of tools able to properly isolate cells in a way that preserves the integrity of the metabolites. My project will use a GEMM of PDAC, congenic markers, and cancer cell-specific surface tags in order to rapidly purify and perform metabolomics of both cancer cells and T-cells. Using this technique, I hope to identify metabolic pathways that are hindering immune cell proliferation and cytotoxic capabilities to reinvigorate the immune microenvironment for tumor control and in response to ICB.

Daniel E. Tracey, Ph.D. Jane Coffin Childs Fellow

Karolinska Institutet

Project Title: Role of antigen binding receptor on lymphocytes in intolerance and immunity

Robert R. Traut, Ph.D. Jane Coffin Childs Fellow

University of Cambridge, England

Project Title: Biochemistry of cells as controlled by genetic units

Tatjana Trcek Pulisic, Ph.D. Jane Coffin Childs - HHMI Fellow

New York University

Project Title: mRNA stability during Drosophila germline

Jessica E. Treisman, Ph.D. Jane Coffin Childs Fellow

University of California, Berkeley

Project Title: Targets of glass in the Drosophila eye disc

John J. Trentin, Ph.D. Jane Coffin Childs Fellow

Yale University

Project Title: Endocrine aspects of mammary gland growth and function

E. Sergio Trombetta, Ph.D. Jane Coffin Childs Fellow

Yale University

Project Title: Role of lectins in glycoprotein folding

Eirini D. Trompouki, Ph.D. Jane Coffin Childs Fellow

Children's Hospital of Boston

Project Title: The role of prostaglandins and Wnt signaling on hemopoietic stem cell renewal

Ian S. Trowbridge, Ph.D. Jane Coffin Childs Fellow

Salk Institute for Biological Studies

Project Title: Cell differentiation

Heather L. True-Krob, Ph.D. Jane Coffin Childs Fellow

University of Chicago

Project Title: Effect of [PSI+] on gene expression

Patricia A. Trumper, Ph.D. Jane Coffin Childs Fellow

Dana-Farber Cancer Institute

Project Title: Early antigen complex of EB virus

Nancy J. Trun, Ph.D. Jane Coffin Childs Fellow

National Cancer Institute

Project Title: Bacterial cell cycle

Benes L. Trus, Ph.D. Jane Coffin Childs Fellow

California Institute of Technology

Project Title: Protein structure

Kaloyan M. Tsanov, Ph.D. Jane Coffin Childs Fellow

Memorial Sloan Kettering Cancer Center

Project Title: The role of ribosomal protein gene deletions in liver cancer

Hemizygous deletions of ribosomal protein genes (RPGs) are recurrently found across human cancers, yet their role in tumorigenesis is poorly understood. Here, I propose to systematically investigate the function of RPG hemizygosity in cancer, using hepatocellular carcinoma (HCC) as a model, by exploring two specific hypotheses. First, based on genomic data from HCC and other tumors, and emerging biochemical evidence for mRNA-specific translational control by individual RPs, I hypothesize that RPGs act as haploinsufficient tumor suppressor genes by selectively altering the translation of oncogenic and/or tumor-suppressive mRNAs. I will assess the contribution of RPG hemizygosity to tumor initiation, progression and maintenance, and analyze its impact on mRNA translation. Second, given that RPG deletions are almost invariably hemizygous and strongly associate with loss of the p53 tumor suppressor gene, I hypothesize that RPG hemizygosity renders cancer cells more vulnerable to perturbations of ribosome homeostasis. I will examine the effects of p53 restoration and further RPG depletion in RPG hemizygous cells, and perform a ribosome homeostasis-focused screen for RPG hemizygosity-specific tumor dependencies. Together, the proposed studies may provide an explanation for the striking patterns of RPG loss in human cancer, with potential broad implications for both fundamental biology and cancer treatment.

Claire C. Tseng, Ph.D. Jane Coffin Childs Fellow

Whitehead Institute

Project Title: Quorum sensing in fungi

Shih-Yi Tseng, M.D., Ph.D. HHMI - Jane Coffin Childs Fellow

University of California, San Francisco

Project Title: Dynamic interactions of hippocampal-prefrontal circuits for flexible behavior

Dr. Shih-Yi Tseng is interested in how the brain coordinates the many functions we use to navigate our way through the world. During her Ph.D. research she studied a large population of neurons to illustrate that neural coding enables these functions and is distributed throughout the cortex. In her fellowship, Tseng will now decipher how two areas of the brain work together to enable the flexible behavior required for navigation.

Tseng’s thesis research in Dr. Christopher Harvey’s lab at Harvard University examined the functional organization of the cortex in supporting sensing, planning, and action to navigate towards a goal location in dynamically changing environments. By tracking the activity of 90,000 brain cells in mice, Tseng found that information about tasks and behavior is spread out across the cortex. Her work suggests that this part of the brain possesses a vast capacity to integrate complex features of behavior and surroundings to guide decisions.

In Dr. Loren Frank’s lab at UC San Francisco, Tseng will now investigate the dynamic interactions between the hippocampus (HPC) and prefrontal cortex (PFC) to enable flexible behavior. The HPC is important for learning and memory, whereas the PFC is crucial for decision-making. These regions need to coordinate during tasks such as navigation, yet how such coordination occurs is not known. Tseng will use multi-area electrophysiology, optogenetic manipulations, and computational methods to determine the HPC-PFC interactions needed for flexible behavior, and to evaluate how their coupling enables these regions to perform their individual functions. This research will provide fundamental insights into HPC-PFC coupling and may reveal ways in which this process goes awry in neuropsychiatric disorders.

Christopher A. Tsu, Ph.D. Jane Coffin Childs Fellow

University of Colorado, Boulder

Project Title: Enzymology of the DEAD family of RNA dependent ATPases

Rocky S. Tuan, Ph.D. Jane Coffin Childs Fellow

Massachusetts General Hospital

Project Title: Vitamin K in normal and neoplastic bone formation

Gregory E. Tullis, Ph.D. Jane Coffin Childs Fellow

Princeton University

Project Title: Molecular interactions of YY1

Jonathan E. Tullis, Ph.D. Jane Coffin Childs Fellow

Oregon Health and Science University

Project Title: Mechanisms of Type I PARP1 Inhibitors in Regulating Cell Fate Decisions in Cancer

Poly ADP-ribose polymerase 1 (PARP1) is a protein involved in the DNA damage response and an important drug target against many cancers. There are a number of PARP1 inhibitors, but current drugs targeting PARP1 can have limited therapeutic potential due to cancer cells frequently acquiring resistance to these drugs.

Dr. Jonathan Tullis aims to understand the mechanistic details of a class of PARP1 inhibitors in Dr. Michael Cohen’s lab at Oregon Health and Science University. PARP1 inhibitors are thought to function by inhibiting the enzymatic activity of this protein. However, “type I” inhibitors exhibit an additional feature – they lock PARP1 onto sites of DNA damage. Dr. Tullis will use mechanistic studies to tease apart the relative importance of these two features – enzymatic inhibition vs locking PARP1 onto DNA – for therapeutic efficacy. These detailed studies promise to reveal novel information about PARP1 biology and may pave the path for more effective PARP1 drugs in the future.

Tullis’ passion for mechanistic studies dissecting protein function stem from his graduate research in Dr. Ulli Bayer’s lab at the University of Colorado. His Ph.D. focused on a protein kinase, CaMKII, that is crucial for long-term potentiation, a fundamental process in learning and memory. It was thought that CaMKII’s kinase activity was required for long-term potentiation. Using careful biochemical and chemical biological approaches, Tullis convincingly demonstrated that it is actually a structural role of CaMKII that is required for inducing long-term potentiation and its enzymatic activity was only required to enable that role. Next, Tullis will leverage his expertise in mechanistic studies to tease apart the important functions of PARP1 inhibitors during his postdoctoral research so that more efficacious targets against cancer cells can be developed.

Glenn C. Turner, Ph.D. Jane Coffin Childs Fellow

California Institute of Technology

Project Title: cAMP and sensory representations in the mushroom body

Gregory E. Turnick Jane Coffin Childs Fellow

Cornell University

Project Title: Ribosome synthesis

Geoffrey Turnock, Ph.D. Jane Coffin Childs Fellow

Cornell University

Project Title: Work on ribosome synthesis

Claudia Turro, Ph.D. Jane Coffin Childs Fellow

Columbia University

Project Title: Time-resolved binding studies of Ru complexes to DNA

Jonathan M. Tyler, Ph.D. Jane Coffin Childs Fellow

University of Alberta

Project Title: Molecular basis of DNA repair

Jayant B. Udgaonkar, Ph.D. Jane Coffin Childs Fellow

Stanford University

Project Title: Mechanism of folding of RNase studies by 2-D NMR

Jay N. Umbreit, M.D., Ph.D. Jane Coffin Childs Fellow

Johns Hopkins University

Project Title: Intercellular adhesion

Elçin Unal, Ph.D. Jane Coffin Childs - HHMI Fellow

Massachusetts Institute of Technology

Project Title: Deciphering the age effects on meiosis and vice versa

Jay C. Unkeless, Ph.D. Jane Coffin Childs Fellow

Massachusetts Institute of Technology

Project Title: Role of proteases of macrophages and lymphocytes in immunological reaction

Wilfred A. Van der Donk, Ph.D. Jane Coffin Childs Fellow

Massachusetts Institute of Technology

Project Title: Mechanistic investigation of ribonucleotide reductases

Susan S. Van Rheenen, Ph.D. Jane Coffin Childs Fellow

Tufts University School of Medicine

Project Title: Intracellular multiplication of legionella

Petra Vande Zande, Ph.D. Jane Coffin Childs Fellow

University of Minnesota

Project Title: Effects of regulatory network divergence on drug resistance in Candida

The human pathogen Candida albicans’ genome varies substantially between clinical isolates, yet it is currently unknown how this variation affects infection. Since many genetic variants are located in gene regulatory sequences, Dr. Petra Vande Zande predicts that there is substantial divergence in gene-regulatory networks between different C. albicans isolates that modifies their fitness. Dr. Vande Zande will use gene expression data from different isolates to model gene regulatory networks and identify key differences that impact fitness. Vande Zande will conduct these experiments in Dr. Anna Selmecki’s lab at the University of Minnesota. This research will provide direct insight into genetic differences that impact C. albicans infections. It may also provide clues into other genetically diverse systems with differences in gene-regulatory networks, including human cancers.

As a graduate student in Dr. Patricia Wittkopp’s lab at the University of Michigan, Vande Zande studied gene expression in the context of adaptive evolution. In particular, Dr. Vande Zande discovered that mutations affecting a gene’s expression from a distance are more pleiotropic and more detrimental to fitness than mutations occurring proximally to the gene of interest. With her experience in the evolution of gene expression, Dr. Vande Zande is now interested in understanding divergence in gene-regulatory networks between different clinical isolates of yeast infections.

Image of Christopher D. Vanderwal, Ph.D.

Christopher D. Vanderwal, Ph.D. Jane Coffin Childs Fellow

Harvard University

Project Title: Large-scale enantioselective synthesis of the microtubule stabilizer FR182877 based on a postulated biogenesis, and studies of its mode action

Frederick S. Varn, Ph.D. Jane Coffin Childs - Merck Fellow

Jackson Laboratory

Project Title: Glioma evolution in the presence of local immune activity

Diffuse glioma is the most common primary brain tumor in adults and is characterized by a poor prognosis and near universal recurrence following therapy. Given the poor response rate to the current standard-of-care, there is an active interest in applying immunotherapy to treat this disease. However, progress on this front has been limited, due in part to limited knowledge of how the immune system interacts with glioma to influence the tumor‚Äôs evolution. My work focuses on how cells of the immune system and accompanying microenvironment interact with malignant cells to influence the developmental trajectory of diffuse glioma. By integrating multi-omic bulk and single-cell datasets from pre- and post-treatment tumors, I aim to develop a better understanding of how gliomas evade the immune response and how the standard-of-care alters these processes. Results from this work can provide insights into how to shape disease progression and enable the sensitization of the gliomas to subsequent treatment approaches.

Inder M. Verma, Ph.D. Jane Coffin Childs Fellow

Massachusetts Institute of Technology

Project Title: Ribonucleic acid synthesis of vesicular stomatitis virus

Kenneth D. Vernick, Ph.D. Jane Coffin Childs Fellow

Carnegie Institution for Science

Project Title: Thyroid hormone receptors in Xenopus metamorphosis

Pablo S. Villar, Ph.D. Jane Coffin Childs Fellow

Harvard University

Project Title: Molecular Basis of Sensory Integration in Octopus

Cells detect and transform specific external stimuli into precise biochemical functions in a process termed signal transduction. Sensory systems are one example of signal transduction. Dr. Pablo Villar will investigate a unique sensory system: octopus chemotactile receptors that mediate contact-dependent aquatic chemosensation. Dr. Villar will use single-cell sequencing, cryo-EM, and physiology to investigate the molecular logic of receptor expression, complex formation, and physiological function in cephalopods. These experiments will be conducted in Dr. Nicholas Bellono’s lab at Harvard University. Villar’s studies will reveal general principles for the evolutionary fine tuning of signal transduction and help connect adaptations in protein structure with octopus behavior.

As a graduate student in Dr. Ricardo Araneda’s lab at the University of Maryland, Villar examined how neuromodulatory brain regions regulate circuits that process sensory information. Specifically, Dr. Villar showed that the basal forebrain activates shortly after the onset of a sensory stimuli, and in a stimulus-specific manner. With this experience in neuroscience and sensory stimuli, Villar will now examine the signal transduction of stimuli at a molecular level in cephalopods.

Luis P. Villarreal, Ph.D. Jane Coffin Childs Fellow

Stanford University

Project Title: Transformation by altered SV40 genomes

Jane E. Visvader, Ph.D. Jane Coffin Childs Fellow

Salk Institute for Biological Studies

Project Title: Function and regulation of the proto-oncogene fos

Mohan Viswanathan, Ph.D. Jane Coffin Childs Fellow

Massachusetts Institute of Technology

Project Title: Calorie restriction and aging in C elegans

Peter D. Vize, Ph.D. Jane Coffin Childs Fellow

Harvard University

Project Title: Molecular response to inductive interactions in vertebrate embryos

Gia K. Voeltz, Ph.D. Jane Coffin Childs Fellow

Harvard Medical School

Project Title: Elucidation of factors involved in ER network formation

Hannah E. Volkman, Ph.D. Jane Coffin Childs - HHMI Fellow

University of Washington

Project Title: Exploring the connections between antiviral responses and autoimmunity

I am interested in how cells recognize and respond to viral pathogens through detection of viral nucleic acids. My research focuses on understanding innate immune pathways involved in cell intrinsic cytosolic DNA detection and coordination of an inducible antiviral response, and how dysregulation of these pathways leads to autoimmune disease.

I grew up on a California farm, surrounded by the natural world, with parents who continually nurtured my interest in it. This experience, coupled with having mentors who allowed me the freedom to follow my interests in their laboratories, have guided my development as a scientist. Freedom to direct my own research has been a tremendous gift, and I am fortunate to be in a truly collaborative research environment. By moving to Seattle I¬† became part of an outstanding research institute, and have also been able to pursue nonacademic interests. I have been on nationally-ranked college and club ultimate frisbee teams,¬† currently help coach the women¬ís ultimate frisbee team at the University of Washington, and compete as a competitive curler. My experiences have created many awesome friendships and helped me develop discipline, determination and leadership skills, while balancing my life as a research scientist.

David A. Vosberg, Ph.D. Jane Coffin Childs Fellow

Harvard Medical School

Project Title: Mechanistic studies of epothilone biosynthesis

Alina M. Vrabioiu, Ph.D. Jane Coffin Childs Fellow

Columbia University

Project Title: Planar cell polarity protein activity and function in developing Drosophila epithelia

Sarah Wacker, Ph.D. Jane Coffin Childs Fellow

Harvard University

Project Title: Dissecting the molecular basis of mutually beneficial interactions between plants and bacteria

Many bacteria form complex multicellular communities known as biofilms. In these communities, cells are encased in a self-produced matrix that shield bacteria from¬†diverse environmental stresses, antimicrobial agents, and host immune systems.¬†Biofilms impact many arenas,¬†including¬†human health, ecology, and agriculture. Due to the importance and ubiquity of biofilms,¬†there is increased interest in investigating the molecular mechanisms underlying the formation and maintenance of these communities.¬†The soil bacterium¬†Bacillus subtilis¬†forms multicellular communities on the roots of some plants, including tomatoes, resulting in increased plant growth.¬†My research examines how environmental signals are sensed by¬†B. subtilis, initiating the biofilm program.

Albert J. J. Wahba, Ph.D. Jane Coffin Childs Fund

New York University

Project Title: Enzyme systems that synthesize nucleic acids

Richard A. Walker, Ph.D. Jane Coffin Childs Fellow

Duke University

Project Title: Cell cycle regulation of cytoplasmic dynein

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.