Directory

Christina Woo Jane Coffin Childs - HHMI Fellow

University of California, Berkeley
Appointed in 2013

Sponsor: Carolyn Bertozzi

My research involves using isotopic labeling strategies and computational methods to enable a novel chemical glycoproteomics platform termed Isotope Targeted Glycoproteomics (IsoTaG).  Given the strong correlation of altered glycosylation patterns with malignancy, glycosylated proteins may be an information-rich subset of the proteome from which cancer biomarkers can be discovered. We employ metabolic labeling as a means to tag specific classes of glycoproteins for enrichment from human tissue samples and subsequent identification by mass spectrometry. A challenge in this endeavor is defining sites of glycosylation on peptide digests derived from such complex samples. To facilitate this effort, we invented a targeted strategy to enable the detection and identification of glycosylated peptides independent of the mass of the pendant glycan. Collectively, these tools allow us to quantitatively profile changes in protein glycosylation associated with human cancer progression and embryonic stem cell differentiation.

Xudong Wu Jane Coffin Childs Fellow

Harvard University Medical School
Appointed in 2015

Sponsor: Tom Rapaport

My research investigates the molecular mechanism of ER-associated degradation (ERAD). Using biochemical and structural tools, my study aims to understand how misfolded proteins in the ER are recognized, retro-translocated out of the ER into the cytosol, and subsequently degraded by proteasome._x000D_
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I was born and grew up in one of the big city in China, Shanghai. After receiving BS in Biology from Fudan University, my strong interest in protein biochemistry brought me overseas to pursue my PhD in molecular biochemistry and biophysics from Yale University. Working in the lab of Karin M. Reinisch, my thesis work focused on solving structures of key regulators of membrane trafficking. Currently, I am doing postdoctoral work supervised by Tom Rapoport, in whose lab I learn new skills in the exciting field of membrane biology. Outside of the lab, I like painting, and enjoy life in Boston with my family and friends.

Kevin Wu, Ph.D. Jane Coffin Childs Fellow

University of California, Berkeley
Appointed in 2023

Sponsor: Dr. Eunyong Park

The endoplasmic reticulum (ER) is a critical organelle for maintaining protein quality control in cells; misfolded proteins are targeted for degradation through the ER-associate degradation (ERAD) pathway. Dr. Kevin Wu will study the ER-membrane bound E3 ubiquitin ligase Doa10 in Dr. Eunyong Park’s lab at the University of California, Berkeley. Doa10 is conserved from yeast to humans and identifies and targets many misfolded proteins for degradation. However, it is unclear how Doa10 recognizes a wide range of client proteins. Dr. Wu will use biochemical and structural approaches to reveal how Doa10 recognizes and processes a range of substrates, and how Doa10 cooperates with other quality control factors to maintain protein homeostasis. Protein misfolding and aggregation are associated with aging and diseases such as neurodegeneration. Thus, Wu’s studies may have implications for developing future therapies to improve protein homeostasis in human disease.

As a graduate student in Dr. James Bardwell’s lab at the University of Michigan, Wu investigated chaperone-mediated protein folding. There, he discovered that weak binding between ATP-independent chaperones enable the refolding of client proteins, whereas stronger binding hinders refolding. Dr. Wu’s background in protein refolding set him up for exploring how Doa10 E3 ubiquitin ligase recognizes unfolded protein targets.

Zeba Wunderlich Jane Coffin Childs Fellow

Harvard University Medical School
Appointed in 2009

Sponsor: Angela DePace

I am currently working on the connection between regulatory region sequence and function by measuring quantitative expression patterns of developmental genes in multiple Drosophila species and creating a biophysical model to interpret these data.

I have always been interested in applying methods from statistics and physics to biological problems. ¬†As an undergraduate at Rutgers University, I majored in molecular biology and statistics and did computational work in a protein NMR lab. ¬†I continued my education in Harvard University’s biophysics program, where I developed mathematical models of a wide variety of biological phenomena, including metabolic networks and protein-DNA interactions. ¬†Following an inspirational summer at the Marine Biological Laboratory¬ís physiology course, I decided to focus my postdoctoral studies on transcriptional regulation, this time combining my computational work with experiments. Outside of my research, I enjoy spending time outside — rowing, running and cross-country skiing.

Gregory Wyant Jane Coffin Childs - HHMI Fellow

Dana-Farber Cancer Institute
Appointed in 2019

Sponsor: William Kaelin

Heart failure is a common and lethal condition, yet the mechanisms by which the heart fails remains a mystery. Over the past decade, heart failure etiology has shifted from valvular heart disease and hypertension to coronary artery disease. As a result, ischemic cardiomyopathy-symptomatic left ventricular (LV) dysfunction in the setting of coronary artery disease- now accounts for nearly 70% of all heart failure causes in the United States. The exact basis of ischemic cardiomyopathy is unknown; however, identifying molecular changes in the ischemic myocardium and the generation of animal models by which these processes can be studied are an absolute necessity.

Hypoxia-inducible factor (HIF), which consists of a labile  subunit and stable  subunit, is master transcription factor that accumulates during hypoxia and activates genes whose products promote cellular survival under ischemic conditions. The HIFsubunit is regulated through prolyl hydroxylation by -ketoglutarate (KG) dependent dioxygenases known as EGLNs (also called PHDs). Acute PHD inactivation in the heart has been shown to be protective during acute cardiac ischemia in rodents, and several PHD inhibitory drugs are now in development as tissue protectant molecules. Conversely, chronic PHD inactivation or HIF stabilization itself, both predictable consequences of chronic ischemia, is sufficient to induce the hallmarks of ischemic cardiomyopathy. My work in William Kaelin’s lab has identified a new mechanism contributing to the pathogenesis of HIF-driven ischemic cardiomyopathy.

Shiyu Xia, Ph.D. Jane Coffin Childs Fellow

California Institute of Technology
Appointed in 2022

Sponsor: Michael Elowitz

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.

Mingshan Xue Jane Coffin Childs - HHMI Fellow

University of California, San Diego
Appointed in 2010

Sponsor: Massimo Scanziani

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.

Katherine Xue Jane Coffin Childs Fellow

Stanford University
Appointed in 2020

Sponsor: Dimitri Petrov and David Relman

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.

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.