Directory

Tepei Y. Yamaguchi Jane Coffin Childs Fellow

University of California, Berkeley
Appointed in 2010

Sponsor: Robert Tjian

Current research: I am studying changes in the core transcriptional machinery during cellular reprogramming

My interest in studying biology was sparked by my growing up in the countryside of Japan, where I always loved to play in nature. After doing undergraduate work at Kyoto University , I received a master’s degree from Kyoto University in Japan, and a PhD from University of Basel, Switzerland. There, I studied the transcriptional regulation of immune cell differentiation, using mouse genetics with Patrick Matthias at the Friedrich Miescher Institute for Biomedical Research. While completing my PhD study, I developed a strong interest in exploring more mechanistic aspects of the transcriptional regulation dictating cellular identity. To pursue this interest, I joined the lab of Robert Tjian at UC Berkeley. Here, I¬ím enjoying not only the great scientific environment, but also outdoor activities and the unique Bay Area culture.

Liewei Yan, Ph.D. Jane Coffin Childs Fellow

Carnegie Institution of Washington
Appointed in 2022

Sponsor: Kamena Kostova

Ribosomes are complex molecular machines that translate mRNAs into proteins and are essential for sustaining life. While the ribosome functions in cellular environments that are markedly diverse, its composition has traditionally been seen as static after assembly. Exciting new studies challenge this concept and provide evidence that organisms assemble different types of ribosomes during development, stress response, or disease. For example, during embryogenesis, zebrafish assemble two types of ribosomes with distinct structures: maternal and somatic. Although this ribosome heterogeneity is predicted to alter protein synthesis, no experimental evidence yet exists to demonstrate this. I will use a multidisciplinary approach to test how changes in ribosome composition affect translation during zebrafish development.

Helen H Yang Jane Coffin Childs - HHMI Fellow

Harvard University Medical School
Appointed in 2018

Sponsor: Rachel Wilson

A long-standing question is how circuits in the brain control motor output, especially given the flexibility that is a hallmark of motor control. Even a seemingly simple action—such as turning the body—can be executed in different ways. For example, a walking fruit fly performs repeated tight turns while foraging locally but more gradual turns while navigating over long distances. Descending neurons (DNs), serving as the bottleneck connecting the brain to the nerve cord, are well-positioned to implement this type of action selection. Here, I propose to characterize the DNs involved in turning behavior in walking Drosophila. I hypothesize that different DN ensembles control distinct turning modes and are differentially recruited during local search and long-range navigation. To test this hypothesis, I will first identify and characterize DNs that are necessary and/or sufficient to evoke different turning modes. Next, I will use optical recording and electrophysiology to investigate how DN activity correlates with turning mode. Finally, I will examine inputs and outputs of these DNs to gain insight into how they are recruited and how they differentially control the legs. Together, these experiments will establish how an ensemble of parallel neural pathways can precisely shape a complex, adaptable behavior.

Zepeng Yao Jane Coffin Childs Fellow

University of California, Berkeley
Appointed in 2017

Sponsor: Kristin Scott

The senses of taste and smell are intimately related, providing an attractive model to study how sensory inputs are integrated. Using the fruit fly Drosophila melanogaster as a model organism, I have found that a fruit-related odorant promotes ingestion of a moderately palatable compound, indicating that taste smell_x000D_
integration occurs in flies and influences feeding decisions. Furthermore, I have identified a subset of olfactory projections neurons that are taste-responsive, suggesting a possible neural mechanism for taste-smell integration. Here, I propose three specific aims to further investigate how sensory detection of_x000D_
taste and smell is integrated in flies. I will examine how tastes and odors interact at the behavioral level (Aim 1), characterize the neural mechanisms that support taste-smell integration (Aim 2), and investigate the behavioral relevance of such mechanisms (Aim 3). The work proposed here will lead to a better understanding of how sensory information is integrated and leads to decisions and actions, and help inform how such processes may be compromised in patients with cancer and brain disorders.

Nathan Yoder Jane Coffin Childs - Merck Fellow

University of California, San Francisco
Appointed in 2020

Sponsor: David Julius

The ability to sense and respond to our external environment is a trait fundamental to the survival of all organisms. One such sense modality, the detection of noxious heat, is accomplished by way of transient receptor potential V1 (TRPV1) ion channels, integral membrane proteins that are also activated by capsaicin and other pungent vanilloid compounds from chili peppers. TRPV1 channels are expressed by afferent neurons of the sensory ganglia and, when exposed to noxious heat, undergo a conformational rearrangement that opens a non-selective pathway for cations across the cell membrane, triggering downstream signaling pathways. By employing a combination of cryo-electron microscopy and electrophysiological techniques, the long-term goal of my research is to define the molecular mechanisms that govern heat detection by TRPV1 and other related ion channels.

Adam Yokom Jane Coffin Childs Fellow

University of California, Berkeley
Appointed in 2018

Sponsor: James Hurley and Roberto Zoncu

My current work focuses on understanding the molecular mechanism of mTORC1 activation and recruitment to the lysosome. Substrate phosphorylation by activated mTORC1 promotes cellular growth and inhibits catabolic pathways such as autophagy. The heptameric Rag:Ragulator complex in response to amino acids and growth factors binds and recruits mTORC1 to the lysosomal surface. Despite recent advancements in our understanding of the mTORC1 pathway, how this fundamental mTORC1:Rag:Ragulator complex forms is still poorly understood. Furthermore, a number of mutations have been identified within RagC for patients with follicular lymphoma which are thought to perturb this interaction hijacking the mTORC1 growth pathway. As a postdoctoral fellow in Hurley lab, my goal is to dissect the conformational states of mTORC1 throughout the activation pathway and capture the interaction with Rag:Ragulator

Oh Kyu Yoon Jane Coffin Childs - HHMI Fellow

University of California, Berkeley
Appointed in 2009

Sponsor: Rachel Brem

The goal of my project is to perform a genome-wide identification of regulatory non-canonical transcripts in budding yeast, using natural genetic variation between outbred individuals. I received my BS and MS in chemistry from Seoul National University, Korea, and an MS in electrical engineering and PhD in chemistry from Stanford University.

My graduate research was on developing a novel mass spectrometer, called Hadamard Transform Time-of-Flight, which has higher spectral scan rate with applications in real-time solution kinetics.

For postdoctoral research, I have made a big switch to genetics and genomics, where I use next-generation sequencing to profile the 3’ UTRs of RNA. In the future, I hope to combine my interdisciplinary expertise to study the regulation of mRNA and protein post-processing, and the effects of their misregulation on human disease.  Outside of the lab, I like to play tennis and drink coffee.

Meg Younger Jane Coffin Childs Fellow

Rockefeller University
Appointed in 2015

Sponsor: Leslie Vosshall

Female mosquitoes require a blood-meal for reproduction, and show intense attraction to human hosts. They rely on host sensory cues, including carbon dioxide (CO2), and components of human body odor, such as lactic acid. These stimuli alone elicit little or no attraction, but in combination they synergize to trigger host-seeking behavior. After obtaining a blood-meal, female host-seeking behavior is switched off for several days. It is unknown where and how any human host cues such as, CO2 in breath, body odor, or body heat, are represented in the mosquito brain. It is also unknown how human host cues synergize to drive host attraction and ultimately trigger biting behavior, or how attraction is suppressed after a blood-meal. I will use two-photon excitation microscopy to measure activity in neural circuits in the mosquito brain to address these questions. This work will provide the first insights into how human cues are processed in the brain of the mosquito Aedes aegypti, which transmits Dengue Fever, Yellow Fever, and Chikungunya. The long-term aim of this research is to find novel approaches to intervene in mosquito biting behavior.

Barry Zee Jane Coffin Childs Fellow

Brigham and Women's Hospital
Appointed in 2014

Sponsor: Mitzi Kuroda

I am interested in how binding of protein modifications contributes to the functions of chromatin complexes. Currently I am developing biochemical and proteomic methods to identify the histone modifications associated with malignant brain tumor (MBT) domain-containing proteins in human tissue culture cells and in fruit flies. The human and fly MBT-containing homologues participate in various aspects of Polycomb group silencing and tumor suppression. Since the MBT domain acts as a methyl lysine-binding module, it is likely that specific modification interactions together with protein interactions enable the localization of otherwise broadly pervasive MBT complexes to specific genomic regions. My graduate training in mass spectrometry complements my postdoctoral training in affinity pulldown of labile interactions with regard to uncovering these potential modification targets.

Quicen Zhang Jane Coffin Childs Fellow

University of Illinois at Urbana-Champaign
Appointed in 2013

Sponsor: Taekjip Ha

Resigned due to health reasons

Jin Zhang Jane Coffin Childs Fellow

Columbia University
Appointed in 2014

Sponsor: Charles Zuker & Tom Maniatis

I am studying the function of the mammalian taste system, in particular the molecular identity and diversity of taste-responsive neurons.  The five basic taste qualities -sweet, sour, salty, bitter and umami, are detected on the tongue and palate epithelium by distinct classes of taste receptor cells (TRCs).  The geniculate ganglion is the first neural station between the tongue and the brain; our lab recently showed that ganglion neurons are also tuned to specific taste qualities.  My studies are aimed at understanding how TRC maintain the highly specific transfer of taste information between taste cells and the central nervous system, particularly given that TRCs turn over every few days.  I have optimized a number of approaches to perform single-cell RNA sequencing both in TRCs and ganglion neurons, and am characterizing and classifying taste neurons into distinct classes.  We hope to define molecular markers that will allow us to manipulate the connectivity, function and behavior of TRCs, and the taste system.

Chen Zhao Jane Coffin Childs - HHMI Fellow

Rockefeller University
Appointed in 2018

Sponsor: Roderick MacKinnon

ATP-sensitive potassium channel (K_ATP) is an ion channel gated by ATP and ADP, and by doing so, it translates the metabolic state of a cell into electric signals. At molecular level, K_ATP is endowed with sensitivity to ATP and ADP through direct interactions with multiple binding sites. These binding sites are scattered across the entire K_ATP molecule, which is a tetramer of hetero-dimers that are composed of a type of inward rectifier potassium ion channel (Kir) and an ABC transporter (SUR).Previous studies have identified an inhibitory site on Kir that results in channel closure upon binding to ATP, and stimulatory sites on SUR that favor channel opening when occupied by either MgADP or MgATP. These observations pose a puzzle because in healthy cells ATP exists at millimolar concentrations whereas ADP is present only in the ten micromolar range. How then does K_ATP detect changes in ADP concentration when the background ATP concentration remains so high that ATP inhibition should dominate? To answer this question, we have to determine what the ATP and ADP affinities are at their respective sites and also understand how occupancy of these sites allosterically regulate the pore’s gate. Once this level of understanding is reached we can then try to predict the response of K_ATP to different metabolic states. Finally, we can integrate these responses into the broader signaling network that involves other closely related partners to describe the action of K_ATP at a systems biology level. My project in the MacKinnon lab aims to address this problem using a combination of electrophysiology and structural biology techniques.

Xu Zhou Jane Coffin Childs Fellow

Yale University School of Medicine
Appointed in 2014

Sponsor: Ruslan Medzhitov

Many human diseases are associated with aberrant inflammation. While the inflammatory response functions to protect an organism against harmful pathogens or to restore tissue homeostasis, excessive inflammation is known to alter tissue functions and damage host tissues. This phenomenon is termed immunopathology and is a major contributor to human morbidity. Therefore, limiting immunopathology is critical in many pathological scenarios. There are two potential means to control immunopathology: to act on immune cells to directly suppress the generation of inflammatory response (“anti-inflammatory” mechanisms), or to act on target tissues to reduce or reverse the deleterious effects caused by inflammation (“counter-inflammatory” mechanisms). A body of previous works has contributed to our knowledge of the anti-inflammatory mechanisms, but the counter-inflammatory mechanisms remain largely elusive. Currently, I am using cellular responses to inflammatory cytokines as the experimental system to identify the counter-inflammatory signals. Meanwhile, I am characterizing their potential mechanisms by taking advantage of the computational and systematic approaches.

Coral Zhou Jane Coffin Childs Fellow

University of California, Berkeley
Appointed in 2018

Sponsor: Rebecca Heald

Our genomes are packaged into functional units of DNA called chromosomes, which are constantly being re-organized and re-shaped to match the demands of the cell. The most dramatic form of this reorganization happens as the cell prepares to divide: chromosomes are replicated, highly condensed, and aligned at center of the mitotic spindle, the complex protein-based machinery that physically separates exactly one copy of the genome to each daughter cell. Errors in this complex sequence of events can result in broken or rearranged chromosomes, known to be a significant source of mutations that drive the progression of many cancer types. A key factor in maintaining genome integrity during cell division is careful regulation of the length of the mitotic chromosome. In studies where chromosomes are artificially lengthened, the mitotic spindle fails at pulling the chromosomes apart, especially when certain cell cycle regulators are depleted. These results suggest that there are molecular pathways that can sense the physical dimensions of a chromosome and communicate this property to downstream regulators of the mitotic machinery. Yet, the exact dimensions being sensed and the molecules involved in this relay of information are still a mystery. Our goal is to identify the molecular pathways that sense, shape and re-enforce chromosome size during cell division. To do this, we will use the vertebrate model system Xenopus laevis, a powerful system for studying how physical dimensions of subcellular structures are determined during embryo development. Previous work from our lab has shown that mitotic chromosomes isolated from embryos in later stages of development are shorter compared to those isolated from early development. These results have provided a launching pad for our proposed work to now identify the molecular pathways that govern this change in size. We aim to (1) characterize how chromosomes are re-organized as they shrink, (2) find the molecules that contribute to these observed size changes and (3) implement the latest advances in imaging technology to test how changes in chromosome size affect embryo development. Because large-scale chromosome rearrangements are a driving force for many cancers, our findings will also provide a foundation for further research into how cancer cells hijack normal chromosome-size control pathways to continue growing and dividing. Also, since cellular behaviors during embryo development are very similar to those in a growing tumor, the tools we will develop to image chromosome dimensions in a growing embryo will greatly enhance our ability to visually assess large-scale chromosome rearrangements in cancer cells, both for research and diagnostics purposes.

Christina Zimanyi Jane Coffin Childs Fellow

Harvard University
Appointed in 2014

Sponsor: Rachelle Gaudet

I am using structural techniques to study pain transduction by transient receptor potential (TRP) ion channels. TRPs comprise a large family of pain sensors activated by diverse stimuli from noxious temperatures to small molecules. My work focuses on understanding the regulation of ion channel opening by such stimuli at the atomic level.

My interest in biochemistry was piqued after taking organic chemistry as an undergraduate at UC Berkeley. I followed my interest in molecular detail to graduate school where I discovered my love for protein structure. During my PhD work at MIT, my studies of the enzyme ribonucleotide reductase led to a thesis focused entirely on allosteric regulation. Since then, I have been intrigued by how proteins use allostery to perform remarkable structural transformations that affect function. TRP channels are master integrators of allosteric signals. They are an ideal system for studying complex allostery and an atomic level understanding of TRP channel activation will provide a foundation for understanding pain.

Naomi Ziv Jane Coffin Childs Fellow

University of California, San Francisco
Appointed in 2016

Sponsor: Alexander Johnson

Transcription circuits, defined as transcription regulators and the DNA cis-regulatory sequences they bind, control the expression of genes and define cellular identity. In eukaryotic cells, regulatory networks tend to be large, containing many highly interconnected transcription factors. Many of these complex networks are bistable, meaning they can toggle between two stable steady states. Bistable networks are responsible for such varied processes such as irreversible decisions during cell cycle progression, embryonic stem cell differentiation and oocyte maturation._x000D_
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I study a bistable transcriptional network in the human commensal yeast Candida albicans that controls an epigenetic switch between two distinct cell types. This network shows many features of those in higher eukaryotes including the high degree of stability of each cell type. The goal of my research is to gain a molecular understanding of the functional differences between the multiple feedback loops present in bistable transcriptional circuits. This analysis will serve as a model for the general understanding of complex circuits.

Roberto Zoncu Jane Coffin Childs - HHMI Fellow

Whitehead Institute for Biomedical Research
Appointed in 2009

Sponsor: David Sabatini

I am studying the molecular mechanisms by which nutrients activate the mTOR kinase, a central regulator of the growth of cells and organisms.

I am a native of Italy, where I earned a BSc in biological sciences from the University of Pisa. I entered the PhD program at Yale to study how membranes are trafficked to and from the surface of the cell, and how these mechanisms contribute to the function of synapses and to neuronal transmission. To this end, I applied advanced live microscopy techniques such as total internal reflection (TIR).  During my PhD work, I became interested in the role of cellular membranes in propagating signals that originate at the cell surface, and how these processes become aberrant in cancer.  To pursue this direction I joined the laboratory of David Sabatini at the Whitehead Institute in 2008. Here, I am combining biochemical techniques with advanced microscopy to investigate how the lysosome, an organelle involved in the degradation and recycling of cellular components, participates in the activation of mTOR complex 1 (mTORC1). In my free time I enjoy running, martial arts, sailing on the Charles River and playing bass in a rock band.