Directory - Jane Coffin Childs Memorial Fund

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Michael S. Levine, Ph.D. Jane Coffin Childs Fellow

University of Basel

Project Title: Characterization of the Drosophila doublesex locus

Robin Levis, Ph.D. Jane Coffin Childs Fellow

National Cancer Institute

Project Title: Hamster polyomavirus

Oded Lewinson, Ph.D. Agouron-Jane Coffin Childs Fellow

California Institute of Technology

Project Title: X-ray crystallography of multidrug transporters

Cristina T. Lewis, Ph.D. Jane Coffin Childs Fellow

Scripps Research Institute

Project Title: Cofactor-assisted catalysis by an antibody

Hao Li, Ph.D. Jane Coffin Childs Fellow

Stanford University

Project Title: Molecular analysis of sex determination gene hermaphrodite

Jing Li, Ph.D. Robertson Foundation-Jane Coffin Childs Fellow

University of California, Berkeley

Project Title: Synthetic modulation of cGAS signaling in mammalian cells

Cells are constantly threatened by pathogens, so they need ways to sense danger and turn on defenses at the right time. In her graduate work, Jing Li, Ph.D., elucidated elegant and mechanistic details of how bacteria know when to fight back against invading bacteriophages. As a Robertson Foundation – Jane Coffin Childs Fellow, Li will leverage insight from her previous studies to reengineer human cells to explore the programmable activation of immune defense.

As a graduate student in Longfei Wang’s lab at Wuhan University, Li revealed how bacterial defense systems sense when to activate. She solved a number of novel and insightful structures of the GajA/GajB proteins with different cofactors and substrates. Her structures showed that when ATP is abundant, GajA remains in a closed, inactive state. However, when ATP is depleted during phage infection, GajA converts into an open state which binds to and cleaves DNA, thereby activating GajB and leading to prokaryotic cell death. This research helped Li appreciate the role of small molecules, such as ATP, to act as information-rich signals that gate biological decisions.

Now in Shiyu Xia’s lab at UC Berkeley, Dr. Li plans to bring similar “small-molecule control” ideas into human cells. She will build synthetic protein circuits to reprogram the cGAS–STING immune pathway so she can choose when it turns on and how strongly it responds. Because cGAS–STING is involved in cancer, aging, autoimmune disease, and infections, this controllable system could help researchers understand these conditions and eventually support new therapies.

Mengyao Li, Ph.D. Robertson Foundation-Jane Coffin Childs Fellow

Broad Institute

Project Title: Decoding the Spatiotemporal Translational Landscape of Early Mammalian Embryogenesis via Developing Spatial Translatomics

How does a single cell develop into a complete and complex organism? Dr. Mengyao Li is fascinated by the question of how cells, despite sharing an identical genome, achieve such distinct identities and tissue types through epigenetic regulation. During her graduate studies in Fuchou Tang’s lab at Peking University and Kehkooi Kee’s lab at Tsinghua University, she traced the epigenetic dynamics and lineage differentiation that guide cell fate decisions during early mammalian embryogenesis, utilizing an ultra-sensitive long-read sequencing-based chromatin accessibility profiling method she developed for scarce, single-cell-input samples. This method enabled her to dissect the epigenetic regulation of repetitive elements and the X chromosome, systematically delineating the cell-type-specific transcription factor regulatory networks that drive early development.

As a Robertson Foundation – Jane Coffin Childs Fellow in Xiao Wang’s lab at the Broad Institute and MIT, she seeks to decipher the hidden spatial code governing how cells translate RNA into functional proteins. By exploring how the subcellular organization of transcripts dictates their translation kinetics, she aims to uncover how dynamic shifts in RNA translational efficiency ultimately orchestrate cellular states, tissue architecture, and disease.

Gen Li, Ph.D. Jane Coffin Childs Fellow

University of California, Berkeley

Project Title: Organophosphorus-Catalyzed Reductive Transformation of Nitro Compounds via P(III)/P(V) Redox Couple

It has long been a focus for the identification of protein drivers and for the development of corresponding cancer therapeutics. Traditionally, drug discovery efforts mainly rely on “druggable” proteins, which possess easily identifiable binding pockets or catalytic active sites. However, over 85% of the proteome is still considered “undruggable”, posing additional challenges for further development. Recently, Activity-Based Protein Profiling, has arisen to spotlight the undruggable proteome via covalent linkage of reactivity-based chemical probes and “ligandable hotspots” in the proteome. In the proposed research, I aim to develop new chemoproteomic platforms based on inexpensive and biocompatible main-group molecules for chemoselective methionine and methionine sulfoxide bioconjugation, to further promote cancer drug discovery. This contribution will be significant because it can develop a ligandability map against undruggable proteome, serve as efficient tools in cancer cell early-stage diagnosis, and further provide a handle to decipher and drug methionine redox regulation in cancer cells, thus yielding novel therapeutics.

Jiefu Li, Ph.D. HHMI-Jane Coffin Childs Fellow

Stanford University

Project Title: Mapping Global and TCR-vicinity proteomic states of T lymphocyte surface

T lymphocytes are central players of our adaptive immune system for fighting against pathogens as well as aberrant self cells. The recognition, action, and modulation of T cells rely on diverse molecules on their surface, including T cell antigen receptors (TCRs) and numerous signaling modulators, such as CTLA-4 and PD-1. Using systems approaches, I study cell-surface signaling of human T cells, with two focuses: 1) I combine TCR repertoire profiling, computational analysis, and scalable antigen screen to quantify TCR repertoire dynamics in infectious diseases and search for population-shared antigens to inspire vaccine development; 2) I build novel tools for spatiotemporally-resolved quantitative proteomics to determine how the T cell surface proteome evolves under distinct cellular states and look for molecular targets for invigorating or modulating T cell activities.

Bo Li, Ph.D. HHMI-Jane Coffin Childs Fellow

Harvard Medical School

Project Title: Unusual redox chemistry in the biosynthesis and action of the dithiolopyrrolone natural product holomycin

Xin Li, Ph.D. Jane Coffin Childs - HHMI Fellow

University of Massachusetts Medical School

Project Title: Understanding the function and regulation of piRNAs in mammals

Lingyin Li, Ph.D. Merck-Jane Coffin Childs Fellow

Harvard Medical School

Project Title: Target cancer with chemical genetics

Xin Li, Ph.D. HHMI-Jane Coffin Childs Fellow

University of Massachusetts Chan Medical School

Project Title: Understanding the function and regulation of piRNAs in mammals

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¬ñCul1¬ñF-box (SCF) complex is one type of cullin¬ñRING ubiquitin ligase (CRL), and its substrate specificity is determined by which one of the 69 different F-box¬ñSkp1 substrate adaptors is recruited to the Cul1 scaffold. Cul1 also binds Cand1 in a manner that is mutually exclusive with F-box¬ñSkp1. Current studies have revealed that Cand1 is a novel exchange factor that equilibrates Cul1 with the total cellular pool of free F-box¬ñSkp1 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.

Ang Li, D.M.D., Ph.D., FAGD Jane Coffin Childs Fellow

Rockefeller University

Project Title: Dissecting the molecular crosstalk that governs melanocyte stem cells in their niche

Wanhe Li, Ph.D. HHMI-Jane Coffin Childs Fellow

Rockefeller University

Project Title: Decoding neuromodulatory control of sleep and wakefulness in Drosophila

The application of Drosophila as a model system has led to many fundamental discoveries concerning the regulation of sleep and wakefulness, including conserved molecular pathways and neural circuits that parallel human studies. Superimposed on the neural circuit wiring diagram are the neuromodulators – biogenic amines and neuropeptides, which are key mediators of the opposing states of sleep and wakefulness. Preliminary research has suggested a novel neuromodulatory circuit in Drosophila that signals arousal and antagonizes sleep. In this proposal, a set of circuit tracing experiments is planned to map this circuit and a novel imaging tool will be developed to visualize peptidergic modulation during states of sleep and wakefulness. In addition, whole-genome transcriptional and translational profiling experiments are proposed to investigate the molecular features of brains under neuromodulatory control. The long-term goal of this proposal is to gain a deep understanding of neuromodulatory processes on genetic, circuit and molecular levels that affect sleep/wake regulation. These studies may also shed light on broader principles of brain function, such as consciousness and memory.

Ke Liang, Ph.D. Jane Coffin Childs Fellow

Harvard Medical School

Project Title: Mechanistic Analysis of Peroxisomal Protein Import Receptor Recycling

Ke Liang, Ph.D. studies how proteins are transported in cells and why these processes matter for human disease. In her earlier work, Liang used structural biology to map major protein-transport machines. As a Jane Coffin Childs Fellow, she will focus on how proteins are transported into peroxisomes, small organelles found in the cytoplasm that act as the cell’s “cleanup crew,” breaking down and detoxifying substances generated by metabolic processes.

As a graduate student in Yigong Shi’s and Zhen Yan’s labs at Westlake University, Liang’s research illuminated different mechanisms for protein transport across organelle boundaries. She made key contributions to determining the structures of the frog cytoplasmic, inner, and nuclear rings of the nuclear pore complex (NPC), providing unprecedented insights of the organization of this complex. Additionally, Liang’s structures of chloroplast protein import complexes in land plants and green algae demonstrated how related transport systems are conserved and specialized across species.

Now as a JCC Fellow in Tom Rapoport’s lab at Harvard Medical School, Liang will investigate protein import into peroxisomes. Peroxisomes are unusual because they can import fully folded proteins using receptors that shuttle in and out and must be extracted and recycled. Liang aims to clarify how these steps work. Because failures in peroxisomal import cause serious diseases with few or no treatments, her work could also point toward new therapeutic ideas.

Brian Liau, Ph.D. Jane Coffin Childs Fellow

Massachusetts General Hospital

Project Title: Activity-based profiling of lysine-specific demethylase 1

My research interests lie at the interface of chemical biology with cancer epigenetics and chromatin biology. In Brad Bernstein¬ís lab, I am currently studying the function of histone demethylases in epigenetic-mediated mechanisms of drug persistence in glioma stem cells. We found that a subpopulation of glioma stem cells indefinitely persist in the presence of potent receptor tyrosine kinase inhibition by entering a slow-cycling state that recapitulates transcriptional and epigenetic features found in primary tumors. In particular, this slow-cycling state is characterized by high histone demethylase expression and widespread chromatin remodeling. We hypothesize that these demethylases may serve as key enablers of epigenetic plasticity in quiescent glioblastoma cells through the removal of chromatin barriers, thus catalyzing the transition to new epigenetic states that promote adaptation, survival, and disease recurrence. We hope to uncover the functions of histone demethylases in glioma and address the potential of attendant therapeutic strategies in neuro-oncology.

Louisa M. Liberman, Ph.D. Jane Coffin Childs Fellow

Duke University

Project Title: Cell-type specific growth regulation in response to cross-kingdom communication

My current research involves investigating cell-type specific growth regulation in response to cross-kingdom communication in Arabidopsis thaliana. ¬†I am interested in learning about the signaling that occurs between plants and microbes in the soil resulting in developmental and physiological changes in the plant.

Raised in Lexington, Massachusetts, I attended Mount Holyoke College, from which I graduated with a double major in biological sciences and Spanish. ¬†I received my PhD working with Angelike Stahopouolos at the California Institute of Technology.

I have always loved puzzles and nature. ¬†Being a scientist means that I have the opportunity to ask questions and learn about how organisms develop and adapt to their environments. ¬†I was drawn to a career in biology because it appeals to my curiosity and provides exciting possibilities to explore what we do not know about nature. When not engaged in my research, I like to spend time outdoors, particularly gardening. ¬†I also enjoy running, biking, skiing, and swimming.

Wen-Hui Lien, Ph.D. Jane Coffin Childs Fellow

Rockefeller University

Project Title: Unraveling the complexities of Wnt signaling in stem cell activation, wound repair and tumorigenesis in the skin

Current research: Understanding differential roles of Wnt signaling ¬ó beta-catenin-Lef/TCF complex in regulation of epidermal homeostasis, hair follicle stem cell maintenance and activation.

My interests in science started in elementary school in my home town of Tapei, Tawain. Later, when my beloved grandfather died of cancer, I was inspired to understand cancer biology.

At Kaohsiung Medical University I did research in molecular biology, for which I received the Undergraduate Innovative Research Award from Taiwan¬ís National Science Council. During my graduate research at the Institute of Molecular Medicine in National Chung Kung University, I became interested in understanding how tumor cells escape from different cancer therapies.

When I came to the U.S., I spent a year at the Fred Hutchinson Cancer Research Center (FHCRC) in Seattle, where my research was to identify novel genes that inhibit myc-induced apoptosis. ¬†¬†My PhD dissertation research at the University of Washington / FHCRC focused on understanding underlying mechanisms and physiological significance of the cell adhesion protein, aE-catenin. After obtaining my PhD in 2008, I received the 2009 Harold M. Weintraub Graduate Student Award. ¬†In April, 2009 I joined the laboratory of Elaine Fuchs at Rockefeller University.

Anthony D . Lien, Ph.D. HHMI-Jane Coffin Childs Fellow

University of California, San Francisco

Project Title: Contribution of basal ganglia-recipient thalamus to cortical motor plans

Daniel CC. Lim, Ph.D. Jane Coffin Childs Fellow

Massachusetts Institute of Technology

Project Title: Characterization of the Pik1 polo-box domain

Jaechul Lim, Ph.D., DVM Jane Coffin Childs Fellow

Yale University

Project Title: Deciphering the mechanism and significance of stress tolerance

Cells continually encounter a variety of suboptimal conditions which restrict growth and proliferation. In response to such stressors, proper adaptive mechanisms are typically activated, which can be categorized into two groups, speciﬁc and general. The stress-speciﬁc responses, such as DNA repair or unfolded protein response, directly deal with the primary cause. By contrast, a common response is assumed to inhibit growth and render cells highly tolerant to the stress as a dormant state of an organism. While most studies have focused on the stress-speciﬁc responses, little is understood about how cells initiate and maintain the common program of stress tolerance. By analyzing sequencing data on various stress conditions, I have found several genes that are commonly regulated in mammalian cells. I hypothesize those genes may modulate stress tolerance which may protect cells from stressors. To understand the role of those candidates, I will 1) determine their targets to unveil regulatory networks and 2) perform in vivo experiments with various stresses to conﬁrm whether the candidates function in the physiological context. By understanding the core stress response, this research will address an important but often overlooked as standing of cell survival and maintenance.

Chi-Yun Lin, Ph.D. Jane Coffin Childs Fellow

Pennsylvania State University

Project Title: Tyrosyl radical relay in proteins:

Protein-based radicals participate in biological processes and natural product biosynthesis that link to life and death in organisms. One remarkable example is class I ribonucleotide reductases (RNRs), which catalyze DNA synthesis with tyrosyl radical relays. To compete for available resources, particularly in pathogens that live in the context of a host, RNRs have evolved distinct cofactors, assembly strategies, and radical translocation mechanisms. Understanding these distinctions from human counterparts is a key step in developing successful anticancer, antimicrobial, and antiviral drugs that inhibit RNRs. However, tyrosines are abundant and form highly cooperative networks, presenting difficulties in isolating their contribution to vectorial redox. I aim to dissect these tyrosines in the newly discovered class I RNRs to probe the free energy landscape of their one-electron oxidation and determine the active state structures. To further advance the field of redox enzyme design for difficult chemical reactions, I will elucidate the crucial protein environmental factors that modulate productive tyrosyl radical relays and prevent detrimental side reactions.

Haifan Lin, Ph.D. Jane Coffin Childs Fellow

Carnegie Institution for Science

Project Title: Genetic analysis of Drosophila oocyte determination

Qing Lin, Ph.D. Jane Coffin Childs Fellow

University of California, Berkeley

Project Title: Expression cloning of Beaten Path receptor

Hening Lin, Ph.D. Jane Coffin Childs Fellow

Harvard Medical School

Project Title: A chemoenzymatic approach to novel antibiotics

Michael Z. Lin, M.D., Ph.D. Jane Coffin Childs Fellow

University of California, San Diego

Project Title: Novel tools for studying neuronal cadherin function

Dayu Lin, Ph.D. HHMI-Jane Coffin Childs Fellow

California Institute of Technology

Project Title: Neural substrates underlying aggressive vs. sexual behavior in mice

John Lin-King, Ph.D. Merck-Jane Coffin Childs Fellow

Stanford University

Project Title: Gut

Chronic pain affects approximately 20% of the adult population in the United States (~50M people), incurring an annual economic impact exceeding 3% US GDP (~$600Bn). This critical public health issue lacks effective treatments beyond classic opiate-based therapies, which itself is a major underlying contributor to the development of the opiate addiction epidemic. Our laboratory has previously found a population of neurons, which are marked by the expression of an opiate receptor and which project from the brainstem to the spinal cord, that are required to facilitate the development chronic pain. We are currently seeking to gain insights into the molecular mechanisms of how these neurons facilitate chronic mechanical hypersensitivity after nerve injury.

More specifically, we have carried out transcriptional profiling of these neurons and found that they selectively upregulate a handful of neuropeptides in the chronic pain state. Currently, we are using RNA-interference to characterize the contribution(s) of individual neuropeptides to the development of chronic pain. With this data in hand, we next aim to identify the cells and corresponding neuropeptide receptor(s) in the spinal cord that are innervated by these neurons. In this way, we will define the peptide-based circuit from brainstem to spinal cord that acts as a gate for the development of chronic pain. Success of this aim will describe a new signaling pathway and therapeutic target(s) that underly the development of this devastating condition.

Dona M. Lindstrom, Ph.D. Jane Coffin Childs Fellow

Cancer Research UK (CRUK) /
University of Colorado

Project Title: Control of SV40 transcription

Xinyu Ling, Ph.D. Merck-Jane Coffin Childs Fellow

Yale University

Project Title: Deciphering the Molecular Mechanisms of Alternative Splicing Regulation via Intronic Transposable Elements

Transposable elements (TEs) play a crucial role in genomic regulation by affecting gene functions, particularly in alternative splicing (AS). Among these, intronic TEs are notably abundant in the human genome, numbering over a million instances. Current research has predominantly fixated on individual TEs near splicing sites, neglecting the vast majority of deep intronic TEs. This oversight hampers our understanding of their collective impact on AS and their relevance to developmental and disease phenotypes. To address this gap, we first start with examining the interaction of TEs within the TBXT gene. TBXT is vital in embryonic development and implicated in tail loss in hominoids and chordoma, a bone cancer where TBXT is aberrantly activated. Exploring these interactions will deepen our knowledge of AS regulation and provide insights into personalized cancer treatment by identifying new genetic markers and therapeutic targets. This research seeks to provide a novel framework to study how the interaction between TEs can affect gene function by modulating pre-mRNA splicing. By uncovering the intricacies of TE-induced AS, we seek to unearth new genetic markers and therapeutic targets, offering novel avenues in disease treatment and prevention.

Maxine Linial, Ph.D. Jane Coffin Childs Fellow

University of Washington /
University of Southern California

Project Title: Viral nucleic acid in cells transformed by avian tumor viruses

Bernt Linzen, Ph.D. Jane Coffin Childs Fellow

Yale University

Project Title: Action of growth substances in insect tissues

Jesse Lipp, Ph.D. Jane Coffin Childs Fellow

University of California, San Francisco

Project Title: A chemical genetics approach on how signaling controls aberrant mRNA splicing in cancer

Barbara B. Lippincott, Ph.D. Jane Coffin Childs Fellow

Laboratoire de Genetique Physiologique, Centre Nationale de la Recherche Scientifique

Project Title: Genetic control of the synthesis of respiratory enzymes in yeast

James A. Lippincott, Ph.D. Jane Coffin Childs Fellow

Laboratoire du Phytrotron, Centre Nationale de la Recherche Scientifique

Project Title: Metabolic effects induced in various plant cells

Carole L. Lipsey Hersh, Ph.D. Jane Coffin Childs Fellow

Stanford University

Project Title: Cellular mechanism for control of protein synthesis

Ryan S. Littlefield, Ph.D. Jane Coffin Childs Fellow

Scripps Research Institute

Project Title: Integrative cytoskeletal model for cell motility

Dan R. Littman, M.D., Ph.D. Jane Coffin Childs Fellow

Columbia University

Project Title: Gene transfer

Xin Liu, Ph.D. Jane Coffin Childs Fellow

Stanford University School of Medicine

Project Title: Structural, biochemical and genetic studies of the role of the trigger loop in substrate specificity and catalysis in RNA polymerase II transcription

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, Ph.D. HHMI-Jane Coffin Childs Fellow

Stanford University

Project Title: Immunoglobulin-domain proteins and synaptic specificity

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.

Siqi Liu , Ph.D. HHMI-Jane Coffin Childs Fellow

Rockefeller University

Project Title: Exploring the mechanism of skin stem cell regulation in skin wound repair

Nian Liu, Ph.D. Jane Coffin Childs Fellow

Stanford University

Project Title: Prion dynamics of transcription factors control cellular differentiation

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, Ph.D. HHMI-Jane Coffin Childs Fellow

Harvard University

Project Title: Neural control of social motivation

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, Ph.D. Jane Coffin Childs Fellow

California Institute of Technology

Project Title: In vivo structure and function of the H. pylori cag type IV secretion system

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‚Äôm 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, Ph.D. HHMI-Jane Coffin Childs Fellow

Harvard Medical School

Project Title: Time to stop: neural mechanisms of action termination

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.

Jialin Liu, Ph.D. Jane Coffin Childs Fellow

University of Michigan

Project Title: Lineage-Guided Evolving CAM Codes in Wiring the Drosophila Brain

Jialin Liu, Ph.D., has been building “snapshots” of brain development using single-cell and spatial gene-expression data. But because those datasets were incomplete, he often had to infer how development unfolded rather than directly observe it. Now he aims to create a new way to track neuronal development in space over time inside an intact brain.

In Joshua Welch, Ph.D.’s lab at The University of Michigan Liu developed computational tools to analyze cell states based on gene expression. Examples include a pipeline that jointly analyzes single-cell sequencing data from a variety of experiments and can be used by all scientists, as well as a model for inferring spatial and temporal dynamics of cell states from spatial transcriptomic data. Liu’s research has provided incredibly useful and broadly accessible tools for analyzing cell state based on gene expression, which can be used to infer cell state transitions among other purposes.

In Tzumin Lee’s lab at The University of Michigan, Liu will generate the kind of data his models need: 3D spatial transcriptomics across multiple time points during fruit fly brain development, both in normal flies and in flies with targeted genetic changes. With these richer datasets and new analysis tools, he hopes to produce a “ground-truth” map of how cell lineages and brain wiring develop over time—more like watching the whole movie rather than predicting from a few frames.

Haoping Liu, Ph.D. Jane Coffin Childs Fellow

Whitehead Institute

Project Title: New targeting pathway in yeast

Fang Liu, Ph.D. Jane Coffin Childs Fellow

Memorial Sloan Kettering Cancer Center

Project Title: Identification and cloning of TGF-beta receptor interacting proteins

Paul M. Lizardi, Ph.D. Jane Coffin Childs Fellow

Carnegie Institution for Science

Project Title: RNA transcription

Wan-Lin Lo, Ph.D. Jane Coffin Childs Fellow

University of California, San Francisco

Project Title: The role of T cell receptor-induced sulfenylation in CD4+ T cell differentiation

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.