Directory

Xin Liu Jane Coffin Childs Fellow

Stanford University School of Medicine
Appointed in 2008

Sponsor: Roger Kornberg

My current research uses a combination of X-ray crystallography, biochemistry, and chemical biology to address the molecular mechanism of transcription preinitiation and initiation by RNA polymerase II. Specific topics include the assembly of the  transcription preinitiation complex, transcription start site selection, and abortive initiation.

My biomedical research training started at Nanjing University, China, where I majored in biochemistry as an undergraduate.  In 2007, I received my PhD in chemistry from the University of Pennsylvania, where I did my thesis study in the laboratory of Ronen Marmorstein at The Wistar Institute. My graduate work centers on the structural and functional studies on the retinoblastoma and p300/CBP tumor suppressor proteins and their regulation by viral oncoproteins. During my graduate study I became fascinated by the broad field of transcription, epigenetics and chromatin, given its enormous impact on human diseases. I joined the laboratory of Roger Kornberg at Stanford University in 2008 and, since then, I have been studying the molecular basis of eukaryotic transcription by RNA polymerase II.

Oliver W. Liu Jane Coffin Childs - HHMI Fellow

Stanford University
Appointed in 2009

Sponsor: Kang Shen

Dendrites of neurons often adopt complex and morphologically diverse branched arbor structures. The development and organization of these arbors fundamentally determine the potential input and connectivity of a given neuron.  My research in the laboratory of Kang Shen has focused on identifying the molecular mechanisms that regulate branching and morphogenesis of neuronal dendrites using the nematode Caenorhabditis elegans as a model system.

Previously, as a graduate student at the University of California, San Francisco,  I worked in the laboratory of Hiten Madhani, where I developed large-scale systematic genetic approaches to identify genes involved in pathogenesis by the human fungal pathogen Cryptococcus neoformans.  As an undergraduate at Harvard University, I worked in the laboratory of Ed Harlow where I studied the mechanisms of transcriptional repression by the tumor suppressor protein pRB.

Xing Liu Jane Coffin Childs Fellow

California Institute of Technology
Appointed in 2013

Sponsor: Raymond Deshaies

Protein function and stability can be modulated by attachment of ubiquitin, which is achieved by three sequentiallyoperating enzymes, of which the last enzyme in the cascade, ubiquitin ligase (E3), confers substrate recognition and ubiquitination. The Skp1–Cul1–F-box (SCF) complex is one type of cullin–RING ubiquitin ligase (CRL), and its substrate specificity is determined by which one of the 69 different F-box–Skp1 substrate adaptors is recruited to the Cul1 scaffold. Cul1 also binds Cand1 in a manner that is mutually exclusive with F-box–Skp1. Current studies have revealed that Cand1 is a novel exchange factor that equilibrates Cul1 with the total cellular pool of free F-box–Skp1 complexes. However, the mechanism and regulation of the Cand1-mediated protein exchange process and the impact of Cand1 on the cellular ubiquitinated proteome remain elusive. This proposal aims to provide insights into the mechanism and significance of Cand1 function through 1) analyzing Cand1-SCF interactions and effects of substrates at millisecond timescales, 2) investigating effects of Cand1 on Cul1 modifications, 3) evaluating changes in CRL assembly and activity in Cand1-depleted cells. These studies will deepen understanding of the biological role of Cand1 and how the repertoire of CRLs is sustained and regulated.

Nian Liu Jane Coffin Childs Fellow

Stanford University
Appointed in 2016

Sponsor: Joanna Wysocka

I am interested in the prion dynamics of transcriptional regulators during human cell development. Lots of transcription factors contain low-complexity domains, which can drive the prion/granule formation. However, little is known about the prion functions or mechanisms of human transcriptional regulators. In our preliminary results, I found that some transcription factors form prions/granules at specific stages of the human neural crest differentiation process and the prions disappear rapidly afterwards. Neural crest cells are a temporary group of cells unique to vertebrates that arise from the embryonic ectoderm cell layer, and in turn give rise to a diverse cell lineage. We hypothesize that the observed prion dynamics of transcription factors are crucial to the neural crest differentiation. As a postdoc in the Wysocka lab at Stanford, I will investigate the regulation factors of the observed prion dynamics as well as the molecular and developmental roles of these prions related to transcription regulation.

Ding Liu Jane Coffin Childs - HHMI Fellow

Harvard University
Appointed in 2017

Sponsor: Catherine Dulac

Social grouping offers social animals unique advantages to survive by decreasing energy consumption, reducing the risk of predation and promoting cooperation. Conversely, social disconnection or isolation can cause negative mental and physical results that motivate animal to re-engage in group. But how social motivation is encoded and regulated in neural circuit remains unclear. In this proposed project, I will identify the brain regions and cell types that are activated during social isolation and re-grouping. Utilizing cell-type targeted calcium imaging, I will monitor the neuronal dynamics during distinct social motivation states and specific social behavioral events. To further investigate underlying circuit-level mechanisms, I will examine the synaptic connections between regions associated with isolation and grouping, and how synaptic strength changes during social isolation. Finally, cell-type and projection specific optogenetic manipulations will be conducted to regulate social motivation and alter the relevant social behaviors. This project will shed new light into the regulation of social motivation both at the cell-type and circuit-levels.

Yuxi Liu Jane Coffin Childs Fellow

California Institute of Technology
Appointed in 2019

Sponsor: Grant Jensen

My project utilizes cryo-electron tomography to study the Dot/Icm type IV secretion system (T4SS) in Legionella pneumophila, the bacterial pathogen responsible for Legionnaires disease. Once inhaled, macrophages engulf L. pneumophila. The latter in turn relies on its T4SS to translocate more than 300 effector proteins into the macrophage, transforming it into a site of replication. Several structural studies have been done to elucidate the T4SS structure in its resting state. I’m particularly interested in the different conformations T4SS adopts at different functional states to accomplish its amazing task. My research will add the molecular mechanism model of how pathogenetic L. pneumophila interacts with hosts and cause diseases. I hope it will also make an impact in the way the scientific community understands the Legionnaires disease and shine light on new treatment approaches.

Shijia Liu Jane Coffin Childs - HHMI Fellow

Harvard Medical School
Appointed in 2024

Sponsor: Bernardo Sabatini, M.D., Ph.D.

Sometimes less is more. Our ability to stop an action is an important aspect of executive control, and the lack of this ability is linked to neuropsychiatric disorders like Obsessive-Compulsive Disorder and Attention-Deficit/Hyperactivity Disorder. Yet, it remains unclear how we make and execute stop decisions.

Dr. Shijia Liu will investigate the neural mechanisms and pathways underlying voluntary stop decisions in Dr. Bernardo Sabatini’s lab at Harvard Medical School. Dr. Liu will focus her studies on how mice voluntarily stop licking in response to the absence of water, as a specific instantiation of the broader question. Liu has designed a “licking-for-water” task that will enable her to dissect this process temporally and in different contexts. She will identify the modes of action and neural pathways that mediate stop decisions using optogenetics, large-scale neural recording, and real-time decoding approaches. Liu’s research will improve our understanding of voluntary stop decisions, related neuropsychiatric disorders, and computational mechanisms for context-dependent behavioral switching.

Liu’s expertise in neuroscience stems from her Ph.D. research in Dr. Sung Han’s lab at the Salk Institute for Biological Studies. Her graduate studies focused on the neural connection between perceived pain and breathing, and how opioid drugs impact this connection. Liu identified two subpopulations of lateral parabrachial nucleus (PBL) neurons that express the m-opioid receptor and project to pain and breathing centers. By manipulating activity at the cellular and molecular levels, Liu discovered how to decouple morphine administration and respiratory depression, which would prevent opioid overdose deaths. With this expertise in involuntary physiological-behavioral connections, Liu will now focus on voluntary decisions and their impact on behavior during her postdoctoral research.

Wan-Lin Lo Jane Coffin Childs Fellow

University of California, San Francisco
Appointed in 2014

Sponsor: Arthur Weiss

The production of reactive oxygen species (ROS) is required for T cell activation and expansion. Dysregulation of ROS-producing NADPH oxidase or mitochondria causes the alteration of T cell function in several clinical diseases, including cancers. ROS modifies T cell receptor (TCR) signaling cascades, in part, through a post-translational modification known as protein sulfenylation. Deprivation of ROS-mediated sulfenylation impaired T cell proliferation and activation, yet elevated ROS rates in tumor microenvironment also suppressed T cell mediated anti-tumor responses. Though the importance of ROS in TCR signaling and hematopoietic malignancies is apparent, little is known about the roles of ROS-mediated sulfenylation in T cell signaling. We propose to introduce a new chemical probe to detect changes in protein sulfenylation directly in primary T cells. We will elucidate how the sulfenylation of key substrates is controlled by ROS generation and TCR stimulation, and also explore biological impacts of non-sulfenylateable key substrates in T cell function and TCR signaling.

Zachery Lonergan Jane Coffin Childs Fellow

California Institute of Technology
Appointed in 2020

Sponsor: Dianne Newman

Energy conservation is an organizing principle for microbial communities. This conservation becomes challenging for bacterial pathogens that must overcome the host immune response. Nonetheless, bacterial infections are major sources of morbidity and mortality, demonstrating that mechanisms exist for pathogens to persist within hosts. Within the lungs of immunocompromised individuals, immune cells are recruited to eliminate pathogens, but this recruitment is unable to clear the infection. Extreme oxygen gradients exist within the lung environment that require metabolic flexibility for bacterial pathogens to survive. While the unique metabolic sources and requirements for microbes within the lungs is not well-defined, we predict that nitrogen oxides serve an important role in supporting bacterial lung persistence. To test this hypothesis, we are implementing geochemical-based strategies to track bacterial nitrogen oxide metabolism, which will provide new conceptual and technical handles on pathogen activities within the human host.

Chin San (Eric) Loo, Ph.D. Jane Coffin Childs - Merck Fellow

Harvard University Medical School
Appointed in 2022

Sponsor: Jun R Huh

The human gastrointestinal tract harbors trillions of microbes that have been coevolving with humans for a long time. Growing evidence suggested that the gut microbiota produces a myriad of metabolites, and some of these small molecules possess bioactivity that can shape host development and fitness, such as modulating gut immune cells and promoting brain development. G protein-coupled receptors (GPCRs) represent the largest class of membrane receptors that relay extracellular cues into a cellular response. Many of these GPCRs including orphan GPCRs may evolutionally be designed for communicating with microbes through microbial metabolites. My research seeks to develop a genetic tool and platform that can characterize ligand-activated GPCRs in vivo and uncover GPCRs that sense microbial metabolites. This work potentially sheds light to understand the underlying mechanisms of host-microbiota interaction.

Christopher Lopez Jane Coffin Childs - Simons Foundation Fellow

Vanderbilt University Medical Center
Appointed in 2017

Sponsor: Eric Skaar

Clostridium difficile is an anaerobic Gram-positive bacterium responsible for nearly half a million intestinal infections in the U.S. annually leading to approximately 29,000 deaths. C. difficile infections (CDI) are most commonly triggered after disruption of the resident microbiota through antibiotics or chemotherapy, which allows C. difficile to subsequently colonize the intestines. CDI can manifest as a spectrum of disease, from mild diarrhea to pseudomembranous colitis or death. Even in situations where patients are treated, recurrent infections are common. While many of the risk factors for CDI are known, there is a general lack of understanding of why CDI presents as such a wide spectrum of disease and what the predictors are for recurrent CDI. My research is aimed at defining how C. difficile adapts to survive in the intestines to cause disease. By understanding the fundamental biology governing C. difficile interactions with the microbiota and the host in the context of infection, we can determine the predictors for disease severity or recurrence and guide the design of effective therapeutics.

Vicki P. Losick Jane Coffin Childs Fellow

Carnegie Institute for Science
Appointed in 2009

Sponsor: Allan Spradling

Identifying cellular mechanisms of tissue repair is critical to our understanding of the normal wound healing process.  I am studying the cellular mechanisms tissues use to respond to damage or injury in the adult Drosophila melanogaster.

As a postdoctoral fellow in Allan Spradling’s laboratory, I am working to combine my former? research expertise in microbiology and innate immunity with the study of cellular processes of tissue repair in the adult fruit fly.  My interest in biomedical research began in college, with an undergraduate research project on viral protein stability.  A particularly influential moment was seeing first-hand the impacts of infectious diseases like malaria during a semester abroad in Kenya.  This experience led me to pursue graduate thesis work at Tufts University. In the laboratory of Ralph Isberg, my project involved characterizing mammalian host cell signaling pathways required for the growth of Legionella, a human pathogen known to cause severe pneumonia.  As part of my professional life, I enjoy mentoring and teaching young scientists. Outside of the lab, I’m an aspiring amateur golfer, jazz enthusiast, and cook.

Dan Ma Jane Coffin Childs Fellow

University of Washington
Appointed in 2015

Sponsor: Wenqing Xu

I’m trying to investigate three dimensional structures of proteins those play important roles in Wnt signaling pathway. Aberrant regulation of Wnt proteins and their signal-transduction cascades are associated with the development of many diseases including some cancers. The aims of my research are to explain the molecular mechanism for Wnt secretion and downstream regulation._x000D_
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I’m from China, and I got my PhD degree at Tsinghua University.  I used to be a structural biologist, and now I’m still a structural biologist, because I think this is a good way for me to understand many biological processes at molecular level.  I mainly focus on structural and biochemical studies of important proteins related with human diseases, and I really hope my research will help people better understand and fight with diseases. Now I’m working as a postdoc in Seattle, a beautiful and romantic city, and I think I will enjoy my research and enjoy my life!

Emily Maclary Jane Coffin Childs - Merck Fellow

University of Utah
Appointed in 2017

Sponsor: Michael Shapiro

Variation in musculoskeletal patterning has major impacts on biodiversity and health: intraspecies variation permits adaptation to different ecological niches, while variation both within and between species plays key roles in evolutionary fitness. Despite this importance, the genetic basis of morphological diversity is largely unknown and remains a central question in developmental biology. Identifying genetic changes that underlie variation in musculoskeletal patterning will expand our understanding of_x000D_
developmental patterning and help to elucidate the origins of biodiversity and the etiology of developmental disorders. The domestic pigeon, Columba livia, is an exceptional model for genetic analysis of morphological changes, as extensive selective breeding has given rise to hundreds of breeds prized for_x000D_
unique morphological traits, including changes in musculoskeletal patterning. Because developmental programs are often highly conserved among vertebrates, this work will help identify gene networks that control patterning across many species, including humans. Prior work has identified variation in axial skeleton patterning and limb musculoskeletal development among breeds of C. livia; this catalog of intraspecies provides a unique opportunity to identify the genes and regulatory networks that control_x000D_
musculoskeletal patterning and development. I will use variation among C. livia breeds to identify and functionally characterize genes involved in musculoskeletal patterning.

Lindsey J. Macpherson Jane Coffin Childs - HHMI Fellow

University of California, San Diego
Appointed in 2008

Sponsor: Charles Zuker

I’m investigating how taste information is encoded at the first relay between taste receptor cells and the gustatory neurons which innervate them. As a third-generation San Diegan who went to the University of California, San Diego as an undergrad and The Scripps Research Institute, La Jolla for graduate school, and who started a postdoc at Charles Zuker¬ís lab at UCSD, I thought I might have beaten the odds and would be able to complete my scientific training in my beloved native city. ¬†Although I had been open to the possibility of moving, I considered myself lucky to be able to live so close to friends and family while pursuing my scientific career at such highly regarded research institutes. So you can imagine my shock when Charles announced his intention to move the laboratory to Columbia University in New York City! ¬†It¬ís been a year since the move, and while I¬ím still a San Diegan at heart, New York has given me a fresh perspective on life and science.

Claire Magnani, Ph.D. Jane Coffin Childs - Merck Fellow

Broad Institute
Appointed in 2022

Sponsor: Stuart Schreiber

There is an urgent need for cancer therapeutics with improved target specificity and novel mechanisms of action. Molecular glues combine the demonstrated capabilities of small molecules as potent drugs with the power of chemically induced proximity. In enabling new protein-protein associations, molecular glues can address many shortcomings of current small molecule cancer therapeutics, which are often limited to protein targets presenting a clear binding pocket. Furthermore, since protein-protein interactions are widely known to facilitate a range of fundamental cellular activities, chemical compounds which intercede on these pathways can provide access to novel mechanisms of action and enhanced target specificity. The wide-ranging therapeutic potential of molecular glue has already been recognized; however, to date the discovery of these compounds has been limited to serendipity or the synthesis of bifunctional molecules. The systematic and generalizable path to molecular glue discovery has not yet been established. In my research, I will leverage the recording and reporting power of DNA encoded libraries to deliver a new path to molecular glue discovery