Directory - Jane Coffin Childs Memorial Fund

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Anna Kotrys, Ph.D. Jane Coffin Childs - HHMI Fellow

Massachusetts General Hospital

Appointed in 2021

Description: Mitochondria are present in nearly all human cells where they play key roles in energy metabolism, biosynthesis, signaling, and cell death. Mitochondrial homeostasis depends on the proper maintenance and expression of the mitochondrial genome (mtDNA). Germline mtDNA mutations can lead to severe, maternally inherited disorders with limited treatment possibilities. Moreover, somatic mtDNA mutations accumulate in neurodegeneration, cancer and aging. mtDNA is a high copy number genome and a mixture of wild-type and mutant mtDNA molecules can co-exist within one cell resulting in “heteroplasmy”. Heteroplasmy dynamics are governed by a complex mix of random drift and selection, but the underlying molecular mechanisms remain unknown. The aim of my post-doctoral research is to uncover the molecular mechanisms that govern mtDNA heteroplasmy. Mechanistic studies of heteroplasmy dynamics will shed the light on the mitochondrial contribution to human health and disease and possibly inspire novel therapeutic approaches to mtDNA disease.

Sharon S. Krag Jane Coffin Childs Fellow

Massachusetts Institute of Technology

Appointed in 1974

Richard B. Krakaur Jane Coffin Childs Fellow

Rockefeller University

Appointed in 1948

Richard A. Kramer Jane Coffin Childs Fellow

Stanford University

Appointed in 1974

Edward T. Krementz Jane Coffin Childs Fellow

Yale University

Appointed in 1948

Thomas M. Kristie Jane Coffin Childs Fellow

Massachusetts Institute of Technology

Appointed in 1987

Andrea Kriz, Ph.D. Jane Coffin Childs - HHMI Fellow

Boston Children's Hospital

Appointed in 2022

While somatic mutations have been heavily studied in tumors, their prevalence and significance to disease risk in healthy individuals is much less well-understood. The Walsh lab and others revealed that somatic mutation is a widespread phenomenon. Human neurons each contain 100 or more clonal somatic single nucleotide variants (sSNV) at birth, acquired during prenatal development, and gain 15-20 additional sSNVs arising per year. Most somatic variants, including those associated with cancer risk, occur in noncoding regions such as enhancers. Despite being the main source of genetic diversity between cells within an individual, the mechanisms by which noncoding somatic mutations form as well as their functional impact are not well understood. My research will focus on developing new strategies to detect rare noncoding somatic variants as well as dissect their epigenomic impact across different cell types in the human brain. This will help illuminate how much this source of variation contributes to cancer risk and brain disease.

Hans Kroeger Jane Coffin Childs Fellow

New York University

Appointed in 1959

Claus-Dieter Kuhn Jane Coffin Childs Fellow

Cold Spring Harbor Laboratory

Appointed in 2008

Urs Kuhnlein Jane Coffin Childs Fellow

Stanford University /
University of Oregon

Appointed in 1970

Richard G. Kulka Jane Coffin Childs Fellow

Case Western Reserve University

Appointed in 1959

Dhivya Kumar Jane Coffin Childs Fellow

University of California, San Francisco

Appointed in 2018

In animals, the centrosome is the major microtubule organizing center and participates intimately in cell division, organelle positioning and key developmental processes, such as neurogenesis. Consequently, centrosome dysregulation can cause defects in chromosome segregation leading to cancer and defects in brain development leading to microcephaly. Surrounding centrosomes are centriolar satellites, 70-100 nm sized, membrane-less organelles. Their functions are mysterious, although recent evidence from my lab suggests that they participate in the assembly of centrosomes and neurogenesis. The molecular mechanisms by which centriolar satellites participate in centrosome function are unknown. Phase separations have recently been shown to be a biophysical mechanism for partitioning subcellular processes. I hypothesized that centriolar satellites are dynamic, phase-separated compartments and that phase separation is essential for trafficking proteins to remodel the centrosome. To test this hypothesis, I am using biophysical, biochemical, genetic and super-resolution live-cell imaging approaches. My work will reveal how phase separation allows centriolar satellites to act as crucibles in which centrosome-bound proteins are dynamically sorted, providing novel insights into how the centrosome is organized and how this organization goes awry in centrosome-related diseases.

Craig E. Kundrot Jane Coffin Childs Fellow

MRC Center, University Medical School, England /
Yale University

Appointed in 1987

Patrick C. Kung Jane Coffin Childs Fellow

Massachusetts Institute of Technology

Appointed in 1974

Prabhat S. Kunwar Jane Coffin Childs Fellow

California Institute of Technology

Appointed in 2008

My research in the lab of David J. Anderson focuses on genetic dissection of neuronal circuitry underlying defensive and offensive behaviors in mice. We use the latest genetic techniques of neuronal marking, mapping and manipulation in order to explain the neuronal basis of these behaviors.

I was born into a middle-class family in a small town in southern Nepal. After finishing high school in my hometown, I began my undergraduate studies in the biology program of Tri-Chandra College in Kathmandu, Nepal.

I considered scientific research early on, as I realized its power both to explain the natural world and our existence, and to bring practical benefits to society. Soon, I became captivated by the spectacular progress in genetics and biomedical sciences. Not seeing any further academic opportunities in the biomedical sciences in Nepal, I came to the U.S., obtaining my undergraduate degree in biotechnology at the University of Nebraska at Omaha. I then did my PhD under the supervision of Ruth Lehmann at New York University Medical Center. I enjoy traveling, and am also involved in promoting biomedical research and education in Nepal via a biomedical society formed by a group of Nepali scientists.

Lawrence C. Kuo Jane Coffin Childs Fellow

Harvard University

Appointed in 1981

Scot C. Kuo Jane Coffin Childs Fellow

Washington University in St. Louis /
Duke University Medical Center

Appointed in 1989

Charlotte Kuperwasser Jane Coffin Childs Fellow

Whitehead Institute for Biomedical Research

Appointed in 2000

Kiyoshi Kurahashi Jane Coffin Childs Fellow

National Institutes of Health

Appointed in 1955

Peri Kurshan Jane Coffin Childs Fellow

Stanford University

Appointed in 2011

Stephen E. Kurtz Jane Coffin Childs Fellow

Columbia University

Appointed in 1986

Naina Kurup Jane Coffin Childs - HHMI Fellow

Harvard University

Appointed in 2018

With global increases in average lifespan, understanding the neurological changes associated with normal aging has become increasingly relevant. Changes in neuronal architecture and synapse function have been proposed to underlie age related cognitive decline in healthy individuals, although the precise mechanisms remain unclear. The neuronal cytoskeleton is essential to the formation of unique neuronal architectures. Advances in superresolution microscopy have enabled the identification of an evolutionarily conserved Membrane-associated Periodic Skeleton (MPS) that forms an integral part of the neuronal cytoskeleton. Mutations in components of the MPS cause neurodegenerative disorders, suggesting that the presence of this network is also important for the maintenance of neuronal function. My project will focus on dissecting the functional role of age related changes to the MPS, providing us with a better understanding of the progressive loss in cognitive ability widespread in the aging population.

Diana J. Laird Jane Coffin Childs Fellow

Sloan Kettering Institute for Cancer Research

Appointed in 2004

Keng-Bon Lam Jane Coffin Childs Fellow

Albert Einstein College of Medicine

Appointed in 1973

Hubert Lam Jane Coffin Childs Fellow

Brigham and Women's Hospital

Appointed in 2007

Teresa M. Lamb Jane Coffin Childs Fellow

Columbia University

Appointed in 1996

Meindert H. Lamers Jane Coffin Childs Fellow

University of California, Berkeley

Appointed in 2004

Terry A. Landers Jane Coffin Childs Fellow

Stanford University

Appointed in 1974

Roger S. Lane Jane Coffin Childs Fellow

University of California, Berkeley

Appointed in 1969

Matthew Lang Jane Coffin Childs Fellow

Stanford University

Appointed in 1999

John P. Langmore Jane Coffin Childs Fellow

MRC Center, University Medical School, England

Appointed in 1975

Nicholas A. Larsen Jane Coffin Childs Fellow

Harvard University Medical School

Appointed in 2003

Benjamin Larson Jane Coffin Childs - Merck Fellow

University of California, San Francisco

Appointed in 2020

I am interested in understanding how cells control shape and movement to thrive in different environments. Although often regarded as simple building blocks, single cells frequently execute surprisingly complex, even animal-like behaviors, which are necessary for proper cellular function. In cells, these behaviors emerge from the joint action of myriad molecular components and interactions between the cell and its environment. How this occurs is poorly understood. To better understand and predict cell behavior, I am working to uncover general principles by studying the coordination of walking in a unicellular organism, the ciliate Euplotes.
How can a single cell, lacking a nervous system, coordinate a gait? While unusual in some ways, Euplotes locomotion is amenable to rigorous behavioral analysis, and many underlying cellular processes and molecular components are deeply conserved among eukaryotes. My work combines theory from computer science and non-equilibrium statistical physics with quantitative microscopy experiments to uncover the mechanisms by which Euplotes coordinates its gait and will develop new theoretical and experimental tools for interrogating the control of complex cellular behaviors.

Dana D. Lasko Jane Coffin Childs Fellow

Imperial Cancer Research Fund Laboratories, England

Appointed in 1986

Andrew B. Lassar Jane Coffin Childs Fellow

Fred Hutchinson Cancer Center

Appointed in 1983

Harrison Latta Jane Coffin Childs Fellow

Massachusetts Institute of Technology

Appointed in 1950

Joyce E. Lauer Jane Coffin Childs Fellow

University of Edinburgh, Scotland

Appointed in 1981

Leander F. Lauffer Jane Coffin Childs Fellow

University of California, San Francisco

Appointed in 1985

Rosalie Lawrence Jane Coffin Childs - HHMI Fellow

University of California, San Francisco

Appointed in 2020

All cells and organisms mount stress response programs in response to external insults; some recover to baseline after stress, while others suffer from side-effects such as chronically altered proteomes that can reduce cellular and organismal fitness. I study the cellular machinery that executes the Integrative Stress Response (ISR), a highly conserved cellular program that rewires translation in the wake of stresses such as nutrient deprivation, viral infection, or redox imbalance. I seek to understand how the ISR machinery remains flexible enough to both respond to diverse stresses and return to baseline, and how dysregulation of the ISR leads to chronic inflammation and memory disorders in higher organisms. I am particularly excited to leverage recent advances in structural biology to go beyond a static understanding and toward uncovering dynamic conformational transitions in cellular ISR machinery that enable nuanced decision-making. To this end, I use hydrogen deuterium exchange, biochemical and cellular assays, and live imaging to study the key ISR actuator eIF2B both in vitro and in cells.

Gregory A. Lazar Jane Coffin Childs Fellow

University of Cambridge, England

Appointed in 1999

Minh T N Le Jane Coffin Childs Fellow

Boston Children's Hospital

Appointed in 2011

Chip Le Jane Coffin Childs Fellow

Harvard University

Appointed in 2020

Catechol dehydroxylation is a highly relevant metabolism in the human gut microbiota with a significant impact on human health. A wide range of neurotransmitters, dietary compounds, and drug molecules have been identified as substrates for this uniquely microbial transformation. However, the ability to predict and manipulate such an important process has been hindered by the limited understanding of enzymes that facilitate the transformation. The Balskus group recently identified dopamine dehydroxylase (Dadh) as the enzyme responsible for the conversion of dopamine to m-tyramine in the gut microbiota. Phylogenetic analysis showed that Dadh and its homologs form a unique DMSO-reductase subfamily. These proteins have not been characterized, and the mechanism has not been deciphered. Moreover, a survey of the human gut microbiome revealed a large number of molybdopterin-dependent enzymes with unknown chemical capability. The main focus of my work is to investigate human gut catechol dehydroxylases via a substrate-guided approach. This work will be accomplished by (1) deciphering the structure and mechanism of dopamine dehydroxylase, (2) biochemically characterizing and comparing reactivity of catechol dehydroxylase homologs, and (3) exploring additional molecular scaffolds that could be susceptible to dehydroxylation by unknown molybdopterin dehydroxylases.

Tim J. Lebetsky Jane Coffin Childs Fellow

California Institute of Technology

Appointed in 2002

Terry L. Lechler Jane Coffin Childs Fellow

Rockefeller University

Appointed in 2002

Joshua Lederberg Jane Coffin Childs Fellow

Yale University /
Columbia University

Appointed in 1946

Hannah Ledvina, Ph.D. Jane Coffin Childs Fellow

University of Colorado, Boulder

Appointed in 2021

Antagonistic interactions are ubiquitous across life. From the conflict between a lion and its prey to the molecular battle between a virus and its host, life is filled with the competition to survive. This has led to the evolution of intricate mechanisms to mediate predatory prey interactions. At the cellular level this has led to the development of immune systems devoted to counteracting attacks and virulence factors dedicated to overcoming these defenses. Over the last several years it has become increasingly clear that bacteria, like humans, possess intricate immune systems to counteract the viruses that invade them, bacteriophages (phage). However, within nature, bacteria face a much wider range of threats than phage and predatory DNA elements. These include neighboring bacteria invading their niche, amoeba seeking out a meal, extracellular toxins, and predatory bacteria. This led us to hypothesize that the bacterial innate immune system has multiple branches capable of defending against this array of threats. But how do you identify a new immune pathway? At this conference, I will present my work developing a technique termed Exploring the Pangenome for Novel Defense (ExPND) which allowed me to uncover and characterize the first genetically encoded mechanism by which Escherichia coli can defend itself against predatory bacteria.

Through the work of numerous groups, it is now clear that the majority of phage defense

systems, the bacterial innate immune components we best understand, are encoded within mobile genetic elements. Therefore, to begin to survey for novel immune systems we obtained a collection of wild E. coli strains collected from natural sources across the globe and, importantly for my work, encodes a wide array of mobile genetic elements. To begin testing our hypothesis I focused on the predatory bacteria Bdellovibrio bacteriovorus. Predatory bacteria, such as Bdellovibrio, robustly and non-selectively prey on Gram-negative bacteria by invading into the periplasm of prey cells and catabolizing cellular components. To date, there are no known genetically encoded resistance mechanism against Bdellovibrio. However, most of the studies investigating this question were performed with lab adapted strains which notoriously lack defense systems. By challenging our E. coli collection with B. bacteriovorus I uncovered

numerous E. coli strains that are highly resistant to predation. Follow-up studies utilizing

transposon mutagenesis have allowed me to identify two mechanisms by which bacteria can

protect themselves including an elaborate extracellular structure that robustly blocks Bdellovibrio predation. By utilizing ExPND, my work sets the foundation for understanding the threats sensed by the bacterial innate immune system and provides a platform for uncovering novel mechanisms at the interface of predator-prey interactions.