Yale University
Appointed in 2004
Predicting membrane Helix interactome
California Institute of Technology
Appointed in 2022
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California Institute of Technology
Appointed in 2022
Synthetic protein circuits a conditional triggers of anti-tumor immunity
By detecting molecular signatures of cancer cells, synthetic protein circuits delivered as mRNA could specifically kill cancer cells. However, a major hurdle is the inability to deliver circuits to all cancer cells in a tumor. An ideal therapy would both selectively eliminate cancer cells to which circuits are successfully delivered and trigger a broader killing effect on the surrounding tumor. Inflammatory cell death that releases immunostimulatory signals provides an ideal mechanism to achieve these two goals by directly killing on-target cancer cells, as well as indirectly killing off-target cancer cells by activating lymphocyte-mediated anti-tumor immunity. Our goal is to design protein-level circuits capable of identifying cancer cells, executing cell death, and eliciting anti-tumor immunity. We will engineer an input module that senses and amplifies oncogenic signals, design an output module that thresholds these signals and actuates inflammatory cell death, and validate the full input-output circuit using cellular and mouse cancer models. Our research will offer a novel immunotherapy concept that combines synthetic biology approaches with the immunotherapy.
Dana-Farber Cancer Institute
Appointed in 2000
Biological analysis of intrinsic CBP HAT function
Stanford University
Appointed in 2020
Adaptation and dispersal in the evolution of microbial communities
The trillions of microbes that live in and on the human body play key roles in health and disease. However, little is known about how microbes evolve in complex communities, even though this evolution can have important consequences for human health. I will study how adaptation and dispersal drive the evolution of antibiotic resistance in microbial communities, both in the human gut microbiome (in vivo) and in experimental, gut-derived microbial communities (ex vivo). First, I will track evolution in the human gut microbiome in a cohort of healthy individuals treated with ciprofloxacin. Using strain-resolved metagenomic sequencing, I will identify selective sweeps and strain replacements to determine how natural microbial communities evolve in response to a disturbance. Next, I will examine how adaptation and dispersal shape the evolution of gut-derived microbial metacommunities. These experimental metacommunities allow me to test how dispersal shapes the rates and mechanisms of adaptation in more controlled, laboratory contexts. Finally, I will study adaptation and transmission in the human gut microbiome by tracking strain transmission in cohabiting individuals before and after antibiotic treatment. This work will combine new computational and experimental approaches to shed light on how microbial communities evolve in the context of human health.
University of California, San Diego
Appointed in 2010
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University of California, San Diego
Appointed in 2010
Circuit analysis of sensory activated neuronal ensembles in mammalian cortex
My current research is focused on understanding the neural circuit mechanism underlying the specific activation of neuronal ensembles by sensory stimuli in the mammalian cortex.
I grew up in a small town in Hunan Province, China. Both my parents are physicians.  In high school, I chanced upon the book, What Mad Pursue by Francis Crick; I was attracted to Dr. Crick’s passion for the “study of life,” and intrigued by the complexity and sophistication of biological systems. I went on to major in biology at Fudan University.
During my senior year, I became interested in neuroscience, and decided to pursuit my graduate study in the US. My graduate research at Baylor College of Medicine focused on the molecular mechanism of synaptic transmission, the process by which neurons communicate with each other.
Now I am extending my scientific interest into the synaptic mechanisms of neural circuit operation in health and disease. In my free time, I like to watch sports, play with our cats and, occasionally, help my wife in her garden.
National Institutes of Health
Appointed in 1958
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National Institutes of Health
Appointed in 1958
Metabolism of compounds with the acetylene bond
University of California, Berkeley
Appointed in 2010
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University of California, Berkeley
Appointed in 2010
Changes in the core transcriptional machinery during cellular reprogramming
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.
Stanford University
Appointed in 1982
Signal transduction in vision
University of California, San Francisco
Appointed in 2005
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University of California, San Francisco
Appointed in 2005
Synthetic feedback shapes MAPK cascade signaling
Carnegie Institution of Washington
Appointed in 2022
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Carnegie Institution of Washington
Appointed in 2022
Determine how ribosome heterogeneity regulates early embyrogenesis
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.
University of California, San Francisco
Appointed in 2003
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University of California, San Francisco
Appointed in 2003
Identification of neuroprotective genes in Drosophila
Harvard University Medical School
Appointed in 2018
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Harvard University Medical School
Appointed in 2018
Investigating the role of descending neurons in flexible motor control
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.
Stanford University
Appointed in 1969
Enzyme-tRNA interactions
University of California, Berkeley
Appointed in 2017
Sensory integration of taste and smell in drosophila
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.
Massachusetts Institute of Technology
Appointed in 1976
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Massachusetts Institute of Technology
Appointed in 1976
Role of elongation factors in DNA synthesis
Harvard University Medical School
Appointed in 2001
Functional assays and crystallization of TAP
Harvard University Medical School
Appointed in 2004
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Harvard University Medical School
Appointed in 2004
Functional genomic approach for protein turnover regulation
Harvard University Medical School
Appointed in 1994
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Harvard University Medical School
Appointed in 1994
Cell cycle regulators of cyclin degradation
University of California, San Francisco
Appointed in 2006
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University of California, San Francisco
Appointed in 2006
Molecular engineering of kinesin motors
Harvard University Medical School
Appointed in 2006
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Harvard University Medical School
Appointed in 2006
Structural characterization of gene silencing complexes
University of California, San Francisco
Appointed in 2020
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University of California, San Francisco
Appointed in 2020
Elucidating thermal gating mechanisms of an ion channel involved in pain
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.
University of California, Berkeley
Appointed in 2018
Mechanism of mTORC1 lysosomal recruitment via Rag:Ragulator
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
University of California, Berkeley
Appointed in 1998
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University of California, Berkeley
Appointed in 1998
California Institute of Technology
Appointed in 1999
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California Institute of Technology
Appointed in 1999
Identifying regulators of cell death in Drosophila
University of California, Berkeley
Appointed in 2009
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University of California, Berkeley
Appointed in 2009
Genome-wide identification of regulatory non-coding RNAs in S. cerevisiae
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.
University of Washington
Appointed in 2007
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University of Washington
Appointed in 2007
Computational redesign of cytochrome P450 function and applications to synthetic biology
Rockefeller University
Appointed in 1983
Purification of cytotoxic proteins from lymphocytes
Salk Institute for Biological Studies
Appointed in 1973
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Salk Institute for Biological Studies
Appointed in 1973
Isolation of SV3Ts growth factors
Rockefeller University
Appointed in 2015
Processing human cues in the mosquito brain
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.
Harvard University
Appointed in 1979
The cloning of B subtilis sporulation genes
University of California, San Francisco
Appointed in 2011
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University of California, San Francisco
Appointed in 2011
Investigating the mechanism of memory recall
University of California, San Francisco
Appointed in 2007
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University of California, San Francisco
Appointed in 2007
Imaging molecular interactions upon ephrin-Eph receptor-mediated adhesion/repulsion responses in live cells
Oxford University, England
Appointed in 1960
Isotopic labelling of various organic substances
Stanford University
Appointed in 1993
Structure/function relationships in anticancer activity
University of California, San Francisco
Appointed in 1982
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University of California, San Francisco
Appointed in 1982
Glucocorticoid-inducible DNase sensitivity
Duke University
Appointed in 1996
In vivo specificity of ribozyme-mediated mRNA repair
University of California, Los Angeles
Appointed in 1993
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University of California, Los Angeles
Appointed in 1993
Role of MAP kinase (ERK) in signal transduction
University of Illinois at Urbana-Champaign
Appointed in 2004
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University of Illinois at Urbana-Champaign
Appointed in 2004
The molecular basis of neurogenesis in planarians
Brigham and Women's Hospital
Appointed in 2014
Analysis of dosage compensation in Drosophila
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.
University of California, Berkeley
Appointed in 2008
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University of California, Berkeley
Appointed in 2008
Comparative genomic analysis of DNA methylation in animals
University of California, Los Angeles
Appointed in 2001
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University of California, Los Angeles
Appointed in 2001
Down syndrome cell adhesion molecule and repulsive axon guidance in Drosophila
Lawrence Berkeley National Laboratory
Appointed in 2004
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Lawrence Berkeley National Laboratory
Appointed in 2004
Single-molecule study of chromatin remodeling
Stanford University School of Medicine
Appointed in 2005
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Stanford University School of Medicine
Appointed in 2005
Vesicle trafficking in neural development
University of Illinois at Urbana-Champaign
Appointed in 2013
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University of Illinois at Urbana-Champaign
Appointed in 2013
Determining the transition of genomic softness in the cancer progression
Resigned due to health reasons
Columbia University
Appointed in 2014
Functional segregation of taste-responsive neurons
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.
New York Genome Center
Appointed in 2020
Functional interactions bewtween the neuronal and immune cells
Massachusetts Institute of Technology
Appointed in 1990
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Massachusetts Institute of Technology
Appointed in 1990
Factors that regulate the activity of the transcriptional activator HAPI
Rockefeller University
Appointed in 2018
Mechanisms of ATP-sensitive potassium, (KATP) channel gating
ATP-sensitive potassium channel (KATP) 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, KATP is endowed with sensitivity to ATP and ADP through direct interactions with multiple binding sites. These binding sites are scattered across the entire KATP 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 KATP 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 KATP 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 KATP 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.
Gladstone Institute
Appointed in 2024
Awarded Sponsor: Dr. Britt Koskella
The molecular biology of Obelisk RNAs
The first century of molecular biology discoveries was enabled by the study of Nature’s original molecular biologists: viruses. Viruses and their simpler cousins, sub-viral RNAs are extremely well adapted to manipulate their host cell. By studying how these agents alter their host, scientists have been able to both understand the mechanisms of diseases as well as derive tools to fight them. Yet there is still much we don’t know about viruses, but even less-so about sub-viral RNAs. Obelisk RNAs are a recently discovered class of widespread sub-viral RNAs with small, structured genomes that seem to bear no resemblance to any known biological entity. The study of Obelisk biology then might reveal molecular mechanisms that have yet to be seen.
Dr. Ivan Zheludev will characterize a novel class of sub-viral RNAs, termed Obelisk RNAs, in Dr. Melanie Ott’s lab at the Gladstone Institute of Virology using a model Obelisk-host system based on a human oral bacterium. Using this system, Zheludev will probe how Obelisk RNA replicates and spreads between cells, the function of the Obelisk-encoded protein Oblin-1, and how Obelisk RNA impacts the host bacterium within complex microbial communities such as the human oral microbiome. Zheludev’s studies will provide foundational knowledge for understanding Obelisk RNAs and provide a general framework for investigating sub-viral RNAs.
Zheludev’s interest in sub-viral RNAs stems from his Ph.D. research in Dr. Andrew Fire’s lab at Stanford University. There, Zheludev created a bioinformatic discovery tool and used it to discover a new class of sub-viral RNAs that he named “Obelisk” RNAs. He demonstrated that Obelisk RNAs are widespread, with examples found on every continent, and that they are diverse, having identified roughly 30,000 distinct Obelisks. Further, they are also found in the microbiomes of between five to fifty percent of assayed human donors. Now in his postdoctoral research, Zheludev will investigate Obelisk molecular biology and their host interactions.
Stanford University School of Medicine
Appointed in 1998
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Stanford University School of Medicine
Appointed in 1998
The roles of Costal2 in hedgehog signaling
Boston Children's Hospital
Appointed in 2022
Deciphering and manipulating death receptor signaling for cancer therapy