Directory - Jane Coffin Childs Memorial Fund

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Year Appointed

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John M. Lyle Jane Coffin Childs Fellow

University of California, San Francisco

Appointed in 2003

Mechanism of microtubule nucleation in the centrosome

Berkeley A. Lynch Jane Coffin Childs Fellow

University of California, Berkeley

Appointed in 1989

Transmembrane regions of the E coli aspartate receptor

Daniel Lyons Jane Coffin Childs Fellow

University of Colorado, Boulder

Appointed in 1999

Regulation of telomere binding protein activity

Chaoyong Ma Jane Coffin Childs Fellow

Harvard University Medical School

Appointed in 1996

Genes encoding bHLH proteins in the mouse retina

Dan Ma Jane Coffin Childs Fellow

University of Washington

Appointed in 2015

Structural study of porcupine, a membrane protein essential to Wnt function

Im 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_
_x000D_
Im from China, and I got my PhD degree at Tsinghua University. I used to be a structural biologist, and now Im 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 Im working as a postdoc in Seattle, a beautiful and romantic city, and I think I will enjoy my research and enjoy my life!

Renata D. Maas Jane Coffin Childs Fellow

New York University

Appointed in 1960

Nucleic acid synthesis

Russell E. MacDonald Jane Coffin Childs Fellow

University of Copenhagen, Denmark

Appointed in 1964

Control mechanisms of cell growth

Bernard Mach Jane Coffin Childs Fellow

Rockefeller University

Appointed in 1964

Mechanisms of synthesis of polypeptides in bacteria

John Maciejowski Jane Coffin Childs - Merck Fellow

Rockefeller University

Appointed in 2014

Can telomere attrition initiate chromosome shattering?

Alyson W. MacInnes Jane Coffin Childs Fellow

Massachusetts Institute of Technology

Appointed in 2004

Emily Maclary Jane Coffin Childs - Merck Fellow

University of Utah

Appointed in 2017

Uncovering the genetic basis of variation in musculoskeletal patterning

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

Molecular characterization of gustatory labeled lines

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

A DNA-encoded library strategy for molecular glue discovery

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

Rohit K. Mahajan Jane Coffin Childs Fellow

University of California, San Francisco /
Scripps Research Institute

Appointed in 1992

Identification of signals for vectorial export of macromolecules from the nucleus

Lara K. Mahal Jane Coffin Childs Fellow

Sloan Kettering Institute for Cancer Research

Appointed in 2000

Identification and characterization of golgi SNARE complexes

Jan E. Maisel Jane Coffin Childs Fellow

University of California, San Francisco

Appointed in 1976

Mechanism of regulation of gene expression in eukaryotic cells

Umadas Maitra Jane Coffin Childs Fellow

Albert Einstein College of Medicine

Appointed in 1963

Initiation and termination of transcription by RNA polymerases

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.