Directory - Jane Coffin Childs Memorial Fund

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Allen Su, Ph.D. Jane Coffin Childs Fellow

Massachusetts Institute of Technology

Project Title: Molecular basis of karyotype evolution in Ewing's sarcoma

My postdoctoral research focuses on how specific aneuploidies benefit tumorigenesis and cancer progression. Over 90% of human solid tumors exhibit aneuploidy, which is characterized by whole chromosome gains and losses. Paradoxically, in normal and untransformed cells aneuploidy impairs cell proliferation, causes many cellular stresses, and is an infrequent occurrence in healthy somatic tissues. I propose to test the hypothesis that aneuploidy promotes tumorigenesis by suppressing oncogenic fitness penalties caused by oncogenic stress. _x000D_
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Since joining the Amon lab in Sept 2016, I have been using Ewing sarcoma (ES) as my research model. Most ES tumors harbor a clear cancer driver mutation, the EWS-FLI1 fusion gene, due to a reciprocal chromosomal translocation between Chromosome 11 and 22. In ES, Chromosome 8 and 12 gains are extremely common and this cancer displays one of the lowest mutational landscapes amongst all cancers. This distinct driver and recurrent aneuploidy makes ES a good model for studying the significance of specific aneuploidies in tumorigenesis. I utilize a tissue culture system and ES patient data (in collaboration with the Stegmaier lab at DFCI) as my research models in this project. With this work in ES, I hope to provide a basis for studies in other cancers that are similarly characterized by specific aneuploidies, such as glioblastomas and B-cell lymphomas.

Suresh Subramani, Ph.D. Jane Coffin Childs Fellow

Stanford University

Project Title: SV40 in non-permissive cells

Woong-Kyung Suh, Ph.D. Jane Coffin Childs Fellow

Harvard School of Public Health

Project Title: Regulation of the c-Maf protooncogene, a Th2-specific transcription factor

Shivang Sullere, Ph.D. HHMI-Jane Coffin Childs Fellow

Harvard University

Project Title: Understanding energetic and vascular constraints on neurophysiology, encoding and behavior.

The brain is a remarkable organ; it shapes our perceptions, memories, and cognitive functions, yet these functions come at a high energetic cost. During Dr. Shivang Sullere’s graduate research he discovered a novel mechanism for pain relief that provides significant insight into the role of endogenous cholinergic circuit, while serving as a potential alternative to opioids. During his fellowship, he will investigate the metabolic, neurophysiological and behavioral consequences of deficient energy supply to active brain regions.

During his Ph.D. research in Dr. Daniel McGehee’s lab at the University of Chicago, Sullere used neurophysiological approaches to explore cholinergic circuits involved in central pain signaling. He identified that activating certain cholinergic centers in the brain helped reduce pain, even in conditions in which opioids no longer worked. He then identified the receptor mechanisms mediating the analgesic effects of this cholinergic circuit.

As he transitions to Dr. Chengua Gu’slab at Harvard University, Sullere will adjust his focus to neurovascular coupling (NVC): a dynamic process that matches local blood flow to areas with high neural activity. He will use genetic mouse models and optical methods to disrupt NVC and evaluate how NVC impacts brain function at metabolic, neurophysiological and behavioral levels. Sullere’s studies will provide foundational insights into NVC and may reveal strategies for correcting metabolic deficits in diseases like Alzheimer’s, dementia, diabetes, and atherosclerosis.

Xiaochen Sun, Ph.D. Jane Coffin Childs Fellow

Stanford University

Project Title: Examining the neural mechanisms for generalization

The ability to learn and memorize is essential for all living organisms to adapt to the ever-changing environment, and it serves as the foundation for higher-order cognitive processes such as reasoning, planning, and decision-making. However, the neuronal basis of memory remains unclear — it is largely unknown how memory-related information is represented by populations of neurons in the brain, and how that representation is formed as a result of learning-induced plasticity. By studying the activity of neurons underlying long-term memory using in vivo imaging and opto/chemogenetics, I hope to understand the neural mechanisms by which new information is learned and processed in neuronal populations. This work will provide insights into the computational principles that govern learning in biological and artificial neural networks.

Xulu Sun, Ph.D. HHMI-Jane Coffin Childs Fellow

University of California, San Francisco

Project Title: Cortical-hippocampal Neural Dynamics Underlying Modelbased Planning

When planning or troubleshooting, we often contemplate possible actions and imagine their outcomes based on prior knowledge. The hippocampus has been implicated in our ability to imagine possible futures, yet it is unclear how future representations are regulated and what functions they subserve. Dr. Xulu Sun will explore the anatomical underpinnings, mechanistic control, and functional significance of hippocampal future representations in Dr. Loren Frank’s lab at the University of California, San Francisco. Dr. Sun will use behavioral tasks and multiregional electrophysiology to explore how the hippocampus interacts with other brain regions to enable future representations and how these representations may support flexible planning. This process is impaired in many neuropsychiatric disorders such as schizophrenia. Thus, Dr. Sun’s research of the underlying neuroscience may reveal new strategies for treating such disorders.

As a PhD student in Dr. Krishna Shenoy‘s lab at Stanford University, Sun investigated dexterous movement control. There she used behavioral tasks and large-scale neural recordings to show how the cortical motor system implements a behavior-organizing map in rhesus monkeys. Dr. Sun will now use her strong foundation in neural computations to explore the neural basis of future representations.

Hong Sun Jane Coffin Childs Fellow

Cold Spring Harbor Laboratory

Project Title: Protein tyrosine phosphatases in PC12 differentiation

Olof H. Sundin, Ph.D. Jane Coffin Childs Fellow

Cold Spring Harbor Laboratory /
MRC Center, University Medical School, England

Project Title: Vertebrate embryology

Melvin G. Sunshine, Ph.D. Jane Coffin Childs Fellow

Karolinska Institutet

Project Title: Interactions between the temperate phage P2 and its host cell, E coli

Zakai Suo, Ph.D. Jane Coffin Childs Fellow

Harvard Medical School

Project Title: Biosynthetic mechanism of yersiniabactin from Yersinia pestis

J. Gregor Sutcliffe, Ph.D. Jane Coffin Childs Fellow

Scripps Research Institute

Project Title: Moloney murine leukemia virus

Hiromi Suzuki, Ph.D. Jane Coffin Childs Fellow

Salk Institute for Biological Studies

Project Title: Mechanisms of biological regulation

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

Cornell University /
University of Utah

Project Title: Classification of exotic ATPase functions using large language models

Can we using large language models to talk to our favorite protein sequence and ask it questions? Dr. Jeff Swan thinks we can! He is developing approaches and tools that leverage foundational protein language models to study mechanisms within the AAA+ (ATPases Associated with diverse cellular Activities) protein superfamily in Dr. Chris Hill’s lab at the University of Utah. Combining this with his experience with hardcore wet lab biochemistry, he aims to help bridge the gap between sequence data and protein function.

As a Ph.D. student in Dr. Carrie Partch‘s lab at the University of California at Santa Cruz, Swan investigated the role of the KaiC, an AAA+ protein that effectuates circadian timing. Dr. Swan demonstrated that the ATPase activity in KaiC imparts cooperativity to the transition between autophosphorylation and autodephosphorylation, which is an important feature of the circadian clock. With his expertise in AAA+ proteins, Dr. Swan is primed to uncover the functional hints interwoven in their protein sequence space.

Jean-Marie Swiecicki, Ph.D. Jane Coffin Childs Fellow

Massachusetts Institute of Technology

Project Title: Interrogating macromolecular interactions at biological membranes

I am passionate about biological processes that occur at cellular membranes. Membranes not only define the borders of cells but also create a fascinating physicochemical environment for a wide diversity of functions. The broad questions that I have been addressing focus on understanding the role of membrane lipids in the function of membrane peptides and membrane protein complexes and developing innovative methods for modulating lipid-peptide or lipid-protein interactions in order to control biological responses._x000D_
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During my graduate research in France under the supervision of Prof. Solange Lavielle and Dr. Fabienne Burlina (at the École Normale Supérieure and the Pierre and Marie Curie University), I studied the spontaneous translocation of peptides through cell membranes that can be used as drug delivery agents. I characterized the translocation event at the molecular level, which provided pertinent clues to the design of drug delivery vectors with enhanced translocation abilities._x000D_
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As a post-doctoral fellow in the laboratory of Prof. Barbara Imperiali (at Massachusetts Institute of Technology), my overarching goal is to decipher the organization and dynamics of supramolecular membrane protein complexes that are part of the N-linked protein glycosylation pathway of pathogenic bacteria. I propose to complement the current methods with an integrated strategy that will merge cell-free membrane protein expression, bioorthogonal labeling and membrane bilayer Nanodiscs. When combined, these technologies will give access to site-specifically labeled membrane-resident protein samples for detailed single-molecule biophysical analysis.

Image of Stuart J. Swiedler , M.D., Ph.D.

Stuart J. Swiedler , M.D., Ph.D. Jane Coffin Childs Fellow

Duke University

Project Title: Structural characterization of mammalian alpha 1, 3-fucosyl-tranferases

Mary H. Sym, Ph.D. Jane Coffin Childs Fellow

University of California, San Francisco

Project Title: Mi9-13 and cell migration

Alexander Symeonidis, M.D. Jane Coffin Childs Fellow

National Institutes of Health

Project Title: Progesterone in mammary carcinogenesis

Supplement to NIH grant

Wlodzimierz Szer, Ph.D. Jane Coffin Childs Fellow

New York University

Project Title: Secondary structure on the messenger function of synthetic polyribonucleotides in protein synthesis

Alexander A. Szewczak, Ph.D. Jane Coffin Childs Fellow

University of Colorado, Boulder

Project Title: RNA folding in the tetrahymena group 1 intron

Clifford J. Tabin, Ph.D. Jane Coffin Childs Fellow

Harvard University

Project Title: Control of early development in Xenopus laevis

Michael R. Tadross, Ph.D. Jane Coffin Childs & Janelia-Jane Coffin Childs Fellow

Stanford University

Project Title: Optogenetic deconstruction of local calcium signaling domains

Calcium signaling is ubiquitous within cells, with numerous implications for cancer biology. I am developing new molecular tools to study spatiotemporal calcium signaling in neurons and other cell types._x000D_
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My interest in biology originally stemmed from a love for math, engineering, and technology. High-school experiences on the computer team, and during a summer internship where I worked with circuits and radar, hooked me on engineering, and led to an undergraduate major in electrical engineering. However, I had a lingering penchant for biology and, during college, when I was exposed to the field of bioengineering, I realized how engineering and biology were truly compatible with one another. Since then, Ive had the privilege of full-immersion into both biology and technology. I received my MD/PhD at Johns Hopkins where my incredible mentor, David Yue, helped me realize how beautiful complexity can arise from simple interactions present within cells, and how calcium, in particular, acts as a universal currency of information transfer within cells. With JCC fellowship support, I plan to develop tools not only to study, but also manipulate calcium signaling in cells tools that will likely be useful in many branches of biological science.

Michiko E. Taga, Ph.D. Jane Coffin Childs Fellow

Massachusetts Institute of Technology

Project Title: Vitamin B12 in rhizobium-legume symbiosis

Yasuyuki Takagi, M.D. Jane Coffin Childs Fellow

National Institutes of Health

Project Title: Nucleic acid synthesis

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

University of California, San Francisco

Project Title: ASH1 mRNA localization in S. cerevisiae

William S. Talbot, Ph.D. Jane Coffin Childs Fellow

University of Oregon

Project Title: Molecular analysis of the zebrafish axial patterning gene floating head

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

University of Colorado, Boulder

Project Title: Trans-acting regulators of homeotic gene function

Frederick J. Tan, Ph.D. HHMI-Jane Coffin Childs Fellow

University of California, Berkeley

Project Title: A genomic study of homologous recombination between repetitive elements

I am interested in understanding how genome structure affects genome function and evolution. ¬†I am studying how chromosome organization limits homologous recombination between dispersed repetitive DNA elements.

I owe my scientific curiosity to two people: my father, who always took the time to answer my questions when I was young, and my high school biology teacher, Dr. Daniel Walsh, who had an endless supply of knowledge and enthusiasm about science. I’m pursuing an academic research career because I believe that one-on-one mentoring between a principal investigator and a graduate students is an ideal training forum.

Previously, I was a lot more active in sports, mostly cycling and running. ¬†These days, however, when I’m not working, my life centers around my wife and our two dogs. ¬†I am still trying to fit in that occasional run!

Yunhao Tan, Ph.D. Merck-Jane Coffin Childs Fellow

Boston Children's Hospital /
Harvard University Medical School

Project Title: Dissecting early host endotoxin sensing mechanisms

My first contact with the field of host and pathogen interaction dated back to the time when I was working at Dr. Feng Shao’s Lab at the National Institute of Biological Sciences, Beijing (NIBS), one of the most prestigious research institute in China.¬†¬† My intern project was to clone and characterize the host substrates of an E3 ubiquitin ligase domain containing effector protein from the vacuolar pathogen Legionella pneumophila. From this experience, I was deeply impressed by the broad array of biochemical mechanisms employed by the bacterial effector proteins to manipulate host functions in order to survive and proliferate inside the host.¬† Furthermore, this experience built up my passion and determination to launch my research journey in host and pathogen interaction.

A year later after my internship, I went on to pursuit my graduate study in Dr. Zhao-Qing Luo¬ís Lab at Purdue University.¬† My research projects have been focused on the manipulation of host membrane trafficking pathways by Legionella effectors. ¬†Specifically, I have discovered that Legionella effector proteins exploited distinct post-translational modification mechanisms, i.e. reversible AMPylation and Phosphorylcholination, to regulate the activities of the host small GTPase Rab1. In summary, these findings highlight the sophisticated nature of host-pathogen interactions and reveals that bacterium has the ability to rewire host signaling events for its own benefit.

Living in the ocean of microorganisms, the innate immune system is the first line of defense to protect host from invading pathogens and to maintain tissue homeostasis.¬† Thus, for my postdoctoral training, I would like to branch out my research focus from microbial pathogenesis into studying the cell biological and biochemical regulatory mechanisms of the host innate immune response.¬† Particularly, I will decipher the spatial-temporal relationships among the earliest cell biological events triggered by endotoxin, such as receptor endocytosis, reactive oxygen production, LC3 associated phagocytosis and SMOC formation.¬† I believe that my proposed research will provide new insights into the previously unexplored area of TLR signaling.

Peilin Tan-Aquino, Ph.D. Jane Coffin Childs Fellow

Dana-Farber Cancer Institute

Project Title: Novel genetic approaches in the study of tumor suppressor VHL

Shiho Tanaka, Ph.D. Jane Coffin Childs Fellow

California Institute of Technology

Project Title: A key to the discovery of new antibacterials: structure determination of an essential bacterial membrane protein, MraY

I grew up in Tokyo, Japan, and came to Los Angeles in 2000 to obtain an undergraduate degree in biochemistry. In my junior year at the ¬†University of California, Los Angeles, I joined the protein expression laboratory under Professor Jeanne Perry’s supervision; there, I was fascinated by x-ray crystallography and decided to go to graduate school to learn more about protein structures and functions. During my¬†graduate study at UCLA, I joined Professor Todd Yeates’ laboratory and determined various structures of shell proteins from bacterial¬†microcompartments. I love southern California and am very happy that I get to stay here to do my post-doctoral work at Caltech.

Weixin Tang, Ph.D. HHMI-Jane Coffin Childs Fellow

Harvard University

Project Title: Development of smart genome-editing agents for targeted therapy

Genetic abnormality is the root cause of many diseases. Canonical therapeutics primarily function by binding to the disease-associated proteins and modulating their activity. The recent advent of programmable sequence-specific endonucleases, however, has raised the possibility of direct manipulation of the corresponding genes and could eventually lead to effective cures of many diseases. The therapeutic potential of genome-editing agents is currently limited due to undesired DNA modifications including activity at off-target DNA sites and activity (on-target or off-target) in cells that are not the target population. My research focuses on developing genome-editing agents responsive to various endogenous and exogenous signals with improved specificity

Mi-Hua Tao, Ph.D. Jane Coffin Childs Fellow

Stanford University

Project Title: A novel vaccine for B-cell lymphoma

Donald F. Tapley, M.D. Jane Coffin Childs Fellow

University of Oxford

Project Title: Factors controlling metabolism at the cellular and sub-cellular level

Justin W. Taraska, Ph.D. Jane Coffin Childs Fellow

University of Washington

Project Title: Imaging dynamics in CNG ion channels

Andrew Taussig, Ph.D. Jane Coffin Childs Fellow

McGill-Montreal General Hospital Research Institute

Project Title: Tumor viruses

C.P.S. Taylor, Ph.D. Jane Coffin Childs Fellow

University of Cambridge, England

Project Title: Mechanism of action of the hemoprotein enzymes

John M. Taylor, Ph.D. Jane Coffin Childs Fellow

Stanford University

Project Title: Characterization of polyribosome-membrane interaction

Kenneth A. Taylor, Ph.D. Jane Coffin Childs Fellow

Medical Research Council (MRC),UKRI

Project Title: Structure of vertebrate striated muscle

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

Whitehead Institute

Project Title: Transport of ribosomal proteins to the yeast nucleus

Gary F. Temple, M.D. Jane Coffin Childs Fellow

Massachusetts Institute of Technology

Project Title: Control of differentiation and development in eukaryotes

Image of Francisco J. Tenjo Castano, Ph.D.

Francisco J. Tenjo Castano, Ph.D. Merck - Jane Coffin Childs Fellow

Columbia University

Project Title: Retro but never outdated: Biology and applications of the human LINE-1 retrotransposon

Francisco Tenjo Castaño, Ph.D. studies how DNA changes over time. In graduate school, he solved new protein structures showing how CRISPR-associated transposons (CAST) insert new DNA into the genomes of their bacterial hosts. As a Jane Coffin Childs-Merck Fellow, he will now study LINE-1, a major human DNA “jumping gene” that can reshape our genome and contribute to disease.

In Guillermo Montoya, Ph.D.’s lab at the University of Copenhagen, Tenjo Castaño used biochemistry and structural biology to reveal the molecular mechanism of CAST DNA insertions. First, he solved the structure of the CAST catalytic protein TnsB bound to the transposon ends and the target DNA, and found that the enzyme only becomes conformationally active when it is properly attached to the target DNA. Tenjo Castaño proposed that this coupling serves as a safety feature to ensure that CAST only starts integrating new DNA into the genome once the complex is in the proper location. Then, he reconstituted the complete ~1 MDa CAST system with target DNA and solved several structures of the entire complex and assembly intermediates at different stages. These results explained the fine details of DNA target detection and insertion site regulation. This work could help advance future gene-editing technologies.

During his thesis research, Tenjo Castaño increasingly appreciated the potential of transposons in gene therapy but also as drug targets. In Akanksha Thawani’s lab at Columbia University, he will focus on LINE-1, the only active autonomous human retrotransposon, which has made up almost one-third of the human genome over evolutionary time. He will identify human proteins that help LINE-1 function, study how LINE-1 works using structural and biochemical methods and look for small-molecule drugs that inhibit it. Because LINE-1 activity is linked to cancer, neurodegeneration, and inflammation during aging, this research could point toward new treatments.

Mabel D. Tettey, Ph.D. Jane Coffin Childs Fellow

National Institute of Allergy and Infectious Diseases

Project Title: Sexual recombination and virulence in the success of African trypanosomes

In disease-causing organisms, hybridization allows for the transfer of traits such as virulence and drug resistance. Dr. Mabel Tettey will investigate how hybridization impacts African trypanosomiasis outbreaks caused by the parasite Trypanosoma brucei. Dr. Tettey will assess the degree of hybridization occurring in African trypanosome endemic areas, explore the impact of hybridization on virulence, and identify the key molecules involved in this process. She will conduct these experiments in Dr. Michael Grigg’s lab at the National Institute of Allergy and Infectious Diseases. These studies may enable the development of effective disease control strategies against African trypanosomes.

As a graduate student in Dr. Keith Matthews’ lab at the University of Edinburgh, Tettey examined the function of released peptidases in the transmission of African trypanosomes. Specifically, Dr. Tettey identified the genes that dominate quorum sensing signal in African trypanosomes. With her extensive background in trypanosome biology, Dr. Tettey will now examine the role of hybridization in trypanosome virulence.

Sheila Teves, Ph.D. Jane Coffin Childs Fellow

University of California, Berkeley

Project Title: Bookmarking the chromosomes and its role in cellular memory

Cellular memory can be defined as the ability of a cell to transmit all its identifying functions to daughter cells during cell division. This ability to ¬ëremember¬í identity is crucial to the development of multicellular organisms, as evidenced when cells lose their identity and degenerate or become cancerous. Conversely, our ability to alter cell state, such as the generation of induced pluripotent stem (iPS) cells from differentiated cells, has become a promising therapeutic tool. Therefore, understanding how cells establish, maintain, and change identity will further our understanding of processes central to cellular development, disease progression, and therapy production. One mechanism for cellular memory is the ability to re-establish the transcriptional program following mitosis, which may function through bookmarking, the process of DNA-binding factors marking genes on condensed mitotic chromosomes to facilitate gene expression following mitosis. The main objective of this proposal is to analyze the mechanisms of bookmarking. I outline three independent approaches to characterize quantitatively the mechanisms of bookmarking. Using these approaches, I will test the hypothesis that histone variants and pluripotency factors function as bookmarkers to maintain the stem cell state. Lastly, I will perform an unbiased screen to identify putative bookmarking factors specific to embryonic stem cells.

Marla Tharp, Ph.D. HHMI-Jane Coffin Childs Fellow

Whitehead Institute

Project Title: Sex diﬀerences in glioblastoma: a microglia perspective

Cancer affects men and women differently. For example, glioblastoma, the most aggressive form of brain cancer, has a male-biased incidence rate and poorer response to standard treatments in men versus women. My research investigates the genetic and molecular basis of sex differences in glioblastoma from the perspective of microglia, the resident immune cells of the brain. Microglia are a major player in the brain tumor microenvironment and promote tumor growth and metastasis. Using XX and XY human microglia isolated from healthy brain regions and brain tumors, I am identifying sex-biased genes and biological pathways that are responsible for establishing sexually dimorphic brain tumor microenvironments. Further, I am testing how possessing an XX or XY sex chromosome complement drives the observed genome-wide sex-biased gene expression patterns in microglia, in particular, through X-linked genes that aberrantly escape X chromosome inactivation or homologous X-Y gene pairs with imbalanced expression or function. I anticipate that my research will lay the groundwork for more effective and sex-specific treatments for glioblastoma.