Directory - Jane Coffin Childs Memorial Fund

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Jaechul Lim Jane Coffin Childs Fellow

Yale University

Appointed in 2018

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.

Daniel Lim Jane Coffin Childs Fellow

Massachusetts Institute of Technology

Appointed in 2003

Characterization of the Pik1 polo-box domain

Hening Lin Jane Coffin Childs Fellow

Harvard University Medical School

Appointed in 2003

A chemoenzymatic approach to novel antibiotics

Michael Z. Lin Jane Coffin Childs Fellow

University of California, San Diego

Appointed in 2005

Novel tools for studying neuronal cadherin function

Dayu Lin Jane Coffin Childs - HHMI Fellow

California Institute of Technology

Appointed in 2007

Neural substrates underlying aggressive vs. sexual behavior in mice

Qing Lin Jane Coffin Childs Fellow

University of California, Berkeley

Appointed in 1998

Expression cloning of Beaten Path receptor

Haifan Lin Jane Coffin Childs Fellow

Carnegie Institute for Science

Appointed in 1990

Genetic analysis of Drosophila oocyte determination

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

Stanford University

Appointed in 2021

A Peptidergic Control Circuit for Chronic Pain

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.

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

Pennsylvania State University

Appointed in 2021

Tyrosyl radical relay in proteins: Emergent class I RNRs as a case study

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.

Dona M. Lindstrom Jane Coffin Childs Fellow

Imperial Cancer Research Fund Laboratories, England /
University of Colorado

Appointed in 1973

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

Broad Institute of MIT and Harvard

Appointed in 2023

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 Jane Coffin Childs Fellow

University of Washington, Seattle /
University of Southern California

Appointed in 1970

Viral nucleic acid in cells transformed by avian tumor viruses

Bernt Linzen Jane Coffin Childs Fellow

Yale University

Appointed in 1960

Action of growth substances in insect tissues

Jesse Lipp Jane Coffin Childs Fellow

University of California, San Francisco

Appointed in 2011

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

Barbara B Lippincott Jane Coffin Childs Fellow

Centre Nationale de la Recherche Scientifique, France

Appointed in 1959

Genetic control of the synthesis of respiratory enzymes in yeast

James A. Lippincott Jane Coffin Childs Fellow

Centre Nationale de la Recherche Scientifique, France

Appointed in 1959

Metabolic effects induced in various plant cells

Carole L. Lipsey Hersh Jane Coffin Childs Fellow

Stanford University

Appointed in 1980

Cellular mechanism for control of protein synthesis

Ryan S. Littlefield Jane Coffin Childs Fellow

Scripps Research Institute

Appointed in 2002

Integrative cytoskeletal model for cell motility

Dan R. Littman Jane Coffin Childs Fellow

Columbia University

Appointed in 1981

Gene transfer

Xin Liu Jane Coffin Childs Fellow

Stanford University School of Medicine

Appointed in 2008

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 Jane Coffin Childs - HHMI Fellow

Stanford University

Appointed in 2009

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.

Haoping Liu Jane Coffin Childs Fellow

Whitehead Institute for Biomedical Research

Appointed in 1992

New targeting pathway in yeast

Fang Liu Jane Coffin Childs Fellow

Memorial Sloan-Kettering Cancer Center

Appointed in 1994

Identification and cloning of TGF-beta receptor interacting proteins

Xing Liu Jane Coffin Childs Fellow

California Institute of Technology

Appointed in 2013

Regulation of cullin-RING ubiquitin ligases by Cand!

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.

Siqi Liu Jane Coffin Childs - HHMI Fellow

Rockefeller University

Appointed in 2015

Exploring the mechanism of skin stem cell regulation in skin wound repairs

Nian Liu Jane Coffin Childs Fellow

Stanford University

Appointed in 2016

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 Jane Coffin Childs - HHMI Fellow

Harvard University

Appointed in 2017

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 Jane Coffin Childs Fellow

California Institute of Technology

Appointed in 2019

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. Jane Coffin Childs - HHMI Fellow

Harvard Medical School

Appointed in 2024

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.

Paul M. Lizardi Jane Coffin Childs Fellow

Carnegie Institute for Science

Appointed in 1971

RNA transcription

Wan-Lin Lo Jane Coffin Childs Fellow

University of California, San Francisco

Appointed in 2014

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.

Raymond E. Lockard Jane Coffin Childs Fellow

Massachusetts Institute of Technology

Appointed in 1972

Sequencing of hemoglobin mRNA

Brenda S. Loewy Jane Coffin Childs Fellow

Columbia University

Appointed in 1986

Developmental regulation of membrane biogenesis

David M. Logan Jane Coffin Childs Fellow

National Institutes of Health

Appointed in 1965

Degradation of mRNA in E. coli

Michael R. Loken Jane Coffin Childs Fellow

Stanford University

Appointed in 1974

Physical and functional characteristics of purified populations of lymphocytes from mice

Zachery Lonergan Jane Coffin Childs Fellow

California Institute of Technology

Appointed in 2020

Bacterial nitric oxide metabolism at the host-pathogen interface

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.

Eric C. Long Jane Coffin Childs Fellow

California Institute of Technology

Appointed in 1989

On demonstrating DNA intercalation

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

Harvard University Medical School

Appointed in 2022

In Vivo tracking of G protein-coupled receptors sensing for gut metabolites

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.

Joseph J. Loparo Jane Coffin Childs Fellow

Harvard University Medical School

Appointed in 2007

Single-molecule enzymology of the replisome

Christopher Lopez Jane Coffin Childs - Simons Foundation Fellow

Vanderbilt University Medical Center

Appointed in 2017

Defining the clostridium difficile responses to zinc limitation

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.

Diego Lopez, Ph.D. Jane Coffin Childs Fellow

University of Utah, Huntsman Cancer Institute

Appointed in 2025

The early-life microbiome regulates β-cell function and type-1 diabetes via gamma-aminobutyric acid

Environmental interactions during prenatal development have important implications that often last well into adulthood. Dr. Diego López’s research has shown how infections can alter this developmental trajectory, impacting immune function and influencing the development of asthma. In his fellowship he will investigate how our microbiome impacts developmental trajectories and metabolic outcomes in adulthood.

López’s graduate research began in Dr. Anna Beaudin’s lab at UC Merced focused on how maternal immune activation and inflammation have lasting impacts that continue well into the offspring’s adulthood.

In one project, Lopez found that when a mother’s immune system is activated, it causes an increase in certain early immune cells—and this increase lasts into adulthood. Additionally, he demonstrated that maternal inflammation expands and hyperactivates a specific population of innate immune cells that cause their offspring to have increased risk for developing asthma in adulthood. Collectively, López’ results reveal the long-lasting consequences of maternal immune activation on offspring fitness.

Now in Dr. June Round’s lab at the University of Utah, López will shift his focus to a different type of environmental interaction: our microbiome. This collection of trillions of microorganisms in our gastrointestinal tract plays a key role in the development of numerous diseases, including type-1 diabetes. Recently, the Round lab demonstrated that loss of early-life microbial diversity during a critical developmental window results in lifelong metabolic dysfunction due to reduced beta cell development. López will investigate the molecular crosstalk between specific microbes, immune cells, and pancreatic beta cells. His research will increase our understanding of the development of type-1 diabetes, and may reveal novel therapeutic targets for treating this disease.

Vicki P. Losick Jane Coffin Childs Fellow

Carnegie Institute for Science

Appointed in 2009

Drosophila melanogaster spermatheca: a new model for the prostate gland

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¬ís 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¬ím an aspiring amateur golfer, jazz enthusiast, and cook.