Directory - Jane Coffin Childs Memorial Fund

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Nairita Maitra, Ph.D. Jane Coffin Childs - HHMI Fellow

Fred Hutchinson Cancer Center

Appointed in 2022

Determining regulation and function of a major microtubule binding pathway

Each time a cell divides, it must ensure equal segregation of chromosomes. Error in this process causes either loss or gain of chromosomes, resulting in aneuploidy, a hallmark of cancer and other diseases. Chromosome segregation is mediated by a megadalton protein complex called kinetochore that assembles at the centromere of each chromosome and serves as the physical linker between chromosomes and the microtubules. Early in mitosis, microtubule-kinetochore attachments are stabilized by tension that distinguishes proper attachment from the improper ones. However, during anaphase, kinetochore-microtubule attachments become vulnerable as tension drops when the chromosomes separate, and the microtubules start shortening. It is major question how kinetochores remain attached to microtubules under low tension. There are two competitive pathways that recruit the major microtubule binding protein, Ndc80c to the kinetochore- Mis12c and CENP-T^Cnn1 pathway. The CENP-T^Cnn1 pathway gets enriched at the kinetochore during anaphase, making it a potential pathway that could stabilize low tension attachments. I hypothesize that the CENP-T^Cnn1 pathway is key to understanding how kinetochores adapt to low tension during anaphase. My goals are to uncover the underlying regulatory mechanism facilitating upregulation of this pathway at the kinetochore during anaphase and how it contributes to kinetochore-microtubule attachments under low tension.

John E. Majors Jane Coffin Childs Fellow

University of California, San Francisco

Appointed in 1978

Mouse mammary tumor virus DNA from infected HTC cells

Nadja Makki Jane Coffin Childs Fellow

Stanford University

Appointed in 2012

Untangling the locus coeruleus noradrenergic neural circuit

My current research aims to explore how DNA regulatory elements influence human development and disease. I am particularly interested in identifying novel enhancers that regulate brain development and identifying mutations within them that lead to neurodevelopmental diseases.

I was born in Germany, where I studied Biology at the University of Goettingen and the University of Kiel. I then came to the US to pursue my Ph.D. in Human Genetics at the University of Utah. My graduate research in the lab of Dr. Mario Capecchi involved examining the role of Hoxa1, a homeobox transcription factor, in early brain development. This sparked my interest in the field of neuroscience and especially in development of the nervous system. I performed a postdoc in Dr. Liqun Luo¬ís lab at Stanford to study the connectivity of individual neurons in the brain. For my current postdoc in Dr. Nadav Ahituv¬ís lab at UCSF, I am focusing on identifying gene regulatory elements that are involved in brain development and examining how changes in the genomic regulatory code can lead to specific phenotypes. Outside the lab, I enjoy the various outdoor activities that the Bay Area has to offer.

Michael H. Malamy Jane Coffin Childs Fellow

Institut Pasteur, France

Appointed in 1963

Genetic control systems

Prerna Malaney Jane Coffin Childs Fellow

MD Anderson Cancer Center

Appointed in 2018

hnRNP K: a putative driver of high risk DLBCL

Aggressive forms of diffuse large B-cell lymphoma (DLBCL) are often marked by genetic alterations at the MYC locus. However, only about 15% of de novo DLBCL cases actually harbor MYC alterations, yet MYC remains overexpressed in many cases alluding to the existence of uncharacterized mechanisms that facilitate its overexpression. Thus, there is a need to identify novel alterations that cause aberrant MYC expression in order to develop effective and targeted therapies. To this end, I have discovered that hnRNP K (Heterogeneous Nuclear Ribonucleoprotein K) is a novel driver of high-risk DLBCL. hnRNP K impacts lymphomagenesis by directly regulating the MYC oncogene via post-transcriptional mechanisms. Elevated MYC levels render hnRNP K-overexpressing cells sensitive to bromodomain inhibitors. Herein, I will determine the mechanistic basis for hnRNP Ks effect on MYC and test the preclinical efficacy of clinically relevant bromodomain inhibitors in hnRNP K-mediated DLBCL. Next, I will interrogate hnRNP K’s impact on therapeutic resistance to bromodomain inhibitors. Lastly, using a high-throughput fluorescence-based assay, I will identify novel compounds that directly disrupt the hnRNP K/MYC transcript interaction.

Thomas Maley Jane Coffin Childs Fellow

Lymphoma Treatment Centre, Uganda

Appointed in 1969

Diagnostic and treatment procedures

Eusebio Manchado Jane Coffin Childs - HHMI Fellow

Memorial Sloan-Kettering Cancer Center

Appointed in 2012

Biological impact of chromosome deletions on tumorigenesis

Venkata S Mandala, Ph.D. Jane Coffin Childs - HHMI Fellow

Rockefeller University

Appointed in 2021

Formation and function of potassium channel signaling clusters in membranesrane

Many transmembrane proteins reside in functionally important clusters on cell membranes. Fluorescence microscopy of membrane proteins in cells has revealed ‘hot spots’ of co-localized proteins such as a_2A-adreneregic G-protein coupled receptors and G proteins participating in signaling complexes. Yet the functional significance of these signaling clusters in cells is not well established. Developing tools to induce controlled clustering of membrane proteins in the lab would thus provide valuable insight into the function of these signaling complexes in cells.

My project proposes three complementary strategies to induce controlled protein clustering in lipid bilayers. The approaches span raft-forming lipid mixtures, tetraspanin and MARVEL domain 4-TM proteins, and membrane-anchored scaffolding proteins with multiple PDZ domains. These tools will be applied to a signaling pathway comprised of G protein-gated K⁺ channels (GIRK) and their activator, the βγ complex of G proteins (Gβγ). The extent of protein clustering and the subsequent effect on activity will be assessed using fluorescence microscopy and electrophysiology

Jerry Manning Jane Coffin Childs Fellow

California Institute of Technology

Appointed in 1973

Integration of DNA from SV40

Colin Manoil Jane Coffin Childs Fellow

Biocentrism der Universitat, Switzerland /
Harvard University

Appointed in 1979

Membrane components involved in E coli conjugation

Tianyang Mao, Ph.D. Jane Coffin Childs Fellow

Broad Institute

Appointed in 2024

LIGHTing up tumor-associated tertiary lymphoid structures through cytokine pharmacokinetic engineering

Proper functioning of our immune systems depends on the precise timing of an orchestra of molecular events. One such important event is the release of cytokines, which are signaling molecules, into the extracellular space to mediate intercellular communication. For cytokines to exert appropriate immunomodulatory roles, their bioavailability must be strictly yet dynamically regulated in space and time. However, the mechanisms by which the immune system interprets the timing of cytokine release remain poorly understood.

Dr. Tianyang Mao will investigate the temporal encoding of cytokine signaling in anti-tumor immunity in Dr. Darrell Irvine’s lab at the Massachusetts Institute of Technology. Dr. Mao will use a novel controlled drug release technology which enables programmable control over the duration of cytokine exposure in vivo. This unique approach will allow Mao to make novel insights into how cytokine temporal dynamics shape cancer immunosurveillance. Better understanding of the immunological impact of cytokine release kinetics will guide the development of temporally reprogrammed cytokine therapeutics for cancer treatment.

Mao’s expertise in immunology emerged as a graduate student in Dr. Akiko Iwasaki’s lab at Yale University. There Mao developed an intramuscular prime–intranasal boost vaccine strategy for SARS-CoV-2 termed “prime and spike,” which leverages preexisting immunity generated by primary mRNA-LNP vaccines to elicit mucosal immunity within the respiratory tract using unadjuvanted intranasal spike boosters. In addition, he developed several antiviral strategies that trigger type I interferon-based immune protection against SARS-CoV-2, including a short stem-loop RNA agonist for the innate immune receptor RIG-I and an aminoglycoside antibiotic with unexpected antiviral properties. Collectively, these strategies hold great promise to not only prevent disease, but also viral transmission. Now, Mao will build on this experience, using novel bioengineering techniques in the Irvine Lab, to make new inroads into the importance of timing in immune responses to cytokines.

Shally Margolis, Ph.D. Jane Coffin Childs Fellow

University of Washington

Appointed in 2022

Mechanisms of Immune Memory Generation in a Native RNA Targeting CRISPR System

CRISPR systems are the adaptive immune systems of bacteria that are crucial for defense against bacteriophage infection. Immune memory is stored as short DNA sequences in the CRISPR array, called “spacers”, and upon transcription and processing these associate with Cas nucleases to search for matching viral targets and initiate nucleic acid cleavage. Type VI CRISPR systems are unique in that they recognize RNA, and target recognition leads the nuclease Cas13 to indiscriminately cleave cellular RNA. While the targeting steps of this CRISPR type are well-understood, it is still unknown how new spacers are acquired, especially since most type VI CRISPR operons lack the known acquisition machinery. Here, we probe the mechanisms of type VI CRISPR immune memory generation using Listeria seeligeri, a genetically tractable host that endogenously encodes type VI CRISPRs. We show that type VI CRISPR can use the adaptation genes from other CRISPR systems in the genome to integrate new memories into the type VI array, both in vivo and in vitro. In addition, we find no clear bias for acquisition of functional, RNA targeting spacers during growth or infection; however, we do observe some bias for acquisition from highly transcribed regions. In the future, we aim to identify additional factors required for acquisition of new spacers in the type VI CRISPR locus and determine the origin of newly acquired spacers.

Robert F. Margolskee Jane Coffin Childs Fellow

Stanford University

Appointed in 1983

Cloning of human low density lipoprotein gene(s)

Brian D. Mariani Jane Coffin Childs Fellow

Harvard University

Appointed in 1983

Temporal specificity of chorion gene expression in Drosophila

Vincent A. Marinkovich Jane Coffin Childs Fellow

MRC Center, University Medical School, England

Appointed in 1961

Medical genetics

Donald D. Mark Jane Coffin Childs Fellow

Rockefeller University

Appointed in 1947

Histochemical study of precancerous lesions

Vadim V. Markovtsov Jane Coffin Childs Fellow

University of California, Los Angeles

Appointed in 1997

Structure of a neuronal splicing enhancer complex

Michele Markstein Jane Coffin Childs Fellow

Harvard University Medical School

Appointed in 2005

Whole-genome RNAi screens to dientify insulator genes

Sudhakar S. Marla Jane Coffin Childs Fellow

Massachusetts Institute of Technology

Appointed in 1997

Platinum oligonucleotides and anticancer drugs

Luciano Marraffini Jane Coffin Childs Fellow

Northwestern University

Appointed in 2008

Mechanisms of sequence-based resistance to bacteriophages and plasmids in Eubacteria

Nicholas R. Marsh-Armstrong Jane Coffin Childs Fellow

Carnegie Institute for Science

Appointed in 1994

Xenopus functional assay for the study of apoptosis

Ian C.B. Marshall Jane Coffin Childs Fellow

Johns Hopkins University

Appointed in 1995

Regulation of nuclear envelope assembly after mitosis

G. Steven Martin Jane Coffin Childs Fellow

University of California, Berkeley

Appointed in 1968

Cell transformation

Sandra L. Martin Jane Coffin Childs Fellow

University of North Carolina

Appointed in 1982

Embryo microinjection

Katherine J. Martin Jane Coffin Childs Fellow

Harvard University

Appointed in 1987

Mechanisms used by eukaryotic transcriptional activator proteins

Gustavo Martinez Jane Coffin Childs Fellow

La Jolla Institute for Allergy and Immunology

Appointed in 2012

Induction of anergy/exhaustion by NFAT1

Nicole Martinez Jane Coffin Childs Fellow

Yale University

Appointed in 2016

Defining the landscape and function of pseudouridines in pre-mRNA

John T. Matschiner Jane Coffin Childs Fellow

University of California, Berkeley

Appointed in 1957

Mouse leukemia

Steven W. Matson Jane Coffin Childs Fellow

Harvard University

Appointed in 1980

T7 DNA replication in vitro

William D. Matthew Jane Coffin Childs Fellow

Harvard University Medical School

Appointed in 1981

Benjamin Matthews Jane Coffin Childs - HHMI Fellow

Rockefeller University

Appointed in 2011

Molecular genetics of water sensation and oviposition site preference the in the yellow fever mosquito

Richard E.F. Matthews Jane Coffin Childs Fellow

University of Wisconsin, Madison

Appointed in 1965

Tumor viruses

Hugh R. Matthews Jane Coffin Childs Fellow

Stanford University

Appointed in 1971

Interaction of the lac-repressor protein with DNA

David A. Matthews Jane Coffin Childs Fellow

University of California, San Diego

Appointed in 1972

Structure determination of the enzyme dihydrofolate reductase

M. Uljana Mayer Jane Coffin Childs Fellow

Pennsylvania State University

Appointed in 2000

Helicase dynamics in DNA replication

Andrew D. McAinsh Jane Coffin Childs Fellow

Massachusetts Institute of Technology

Appointed in 2001

Gretchen McCaffrey Jane Coffin Childs Fellow

University of California, San Francisco

Appointed in 1988

Kinesin's biological roles, a genetic approach

William H. McClain Jane Coffin Childs Fellow

MRC Center, University Medical School, England

Appointed in 1969

Structure and function in tRNA

Alison McCormick Jane Coffin Childs Fellow

Stanford University

Appointed in 1990

Transcriptional regulation by homeotic genes

Image of Margaret (Meghan) McDaniel, Ph.D.

Margaret (Meghan) McDaniel, Ph.D. Jane Coffin Childs Fellow

University of Washington

Appointed in 2022

Tissue Specific Sentinels of Type 2 Immunity

The innate immune system is paramount in recognizing foreign or mutated material and initiating proper immune responses to combat them. Recognition of allergens and parasitic worms (helminths) elicit a socalled “type 2” immune response focused on expulsion of stimuli and tissue repair. Type 2 immune responses impact the prognosis of many cancers and the success of immunotherapies, but how these responses are established remains poorly understood. Group 2 innate lymphoid cells (ILC2s) initiate and propagate type 2 immune responses, but do not sense immune agonists directly. The origin and regulation of host-derived signals leading to ILC2 activation is therefore an area of immense interest. Recent work identified a specialized population of epithelial tuft cells responsible for sensing helminths and activating ILC2s by secreting interleukin(IL)-25 and cysteinyl leukotrienes in the small intestine. Airway ILC2s are similarly important for type 2 immune responses in the lung, but tuft cells are dispensable in this context. My proposal seeks to identify the signals that activate intestinal tuft cells and a novel cell subset responsible for airway ILC2 activation. Examining the initiation of type 2 immunity in multiple organs will uncover both convergent and divergent mechanisms by which type 2 responses can be further manipulated.