Massachusetts Institute of Technology
Appointed in 1974
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Massachusetts Institute of Technology
Appointed in 1974
Subcellular localization of glycolipid changes during viral transformation
Rockefeller University
Appointed in 1948
Purification and crystallization of enzymes and proteins
Stanford University
Appointed in 1974
RNA synthesis from fragments of eukaryotic genomes
Yale University
Appointed in 1948
Tumors of neural origin
Massachusetts Institute of Technology
Appointed in 1987
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Massachusetts Institute of Technology
Appointed in 1987
Repression of enhancer activity by adenovirus E1A
Boston Children's Hospital
Appointed in 2022
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Boston Children's Hospital
Appointed in 2022
Dissecting the impact of non-coding somatic mutations in the human brain
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.
New York University
Appointed in 1959
Influence of DNA on synthesis of RNA
Cold Spring Harbor Laboratory
Appointed in 2008
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Cold Spring Harbor Laboratory
Appointed in 2008
RabGDI displacement factors: mechanism and function in membrane traffic
Stanford University /
University of Oregon
Appointed in 1970
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Stanford University / University of Oregon
Appointed in 1970
Enzyme recognition of base sequences on DNA
Case Western Reserve University
Appointed in 1959
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Case Western Reserve University
Appointed in 1959
Stanford University /
Rockefeller University
Appointed in 2010
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Stanford University / Rockefeller University
Appointed in 2010
Centrosomes and the regulation of asymmetric cell division
University of California, San Francisco
Appointed in 2018
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University of California, San Francisco
Appointed in 2018
Centriolar satellites use phase separation to remodel the centrosome
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.
MRC Center, University Medical School, England /
Yale University
Appointed in 1987
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MRC Center, University Medical School, England / Yale University
Appointed in 1987
Cloning and crystallization of TFIIIA Zn-binding domains
Massachusetts Institute of Technology
Appointed in 1974
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Massachusetts Institute of Technology
Appointed in 1974
Role of terminal deoxynucleotidyl transferase in developing thymus
California Institute of Technology
Appointed in 2008
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California Institute of Technology
Appointed in 2008
Genetic dissection of amygdala neuronal circuitry underlying fear and anxiety in mice
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.
Harvard University
Appointed in 1981
Catalysis and regulation of ornithine transcarbamylase
Washington University in St. Louis /
Duke University Medical Center
Appointed in 1989
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Washington University in St. Louis / Duke University Medical Center
Appointed in 1989
Microtubule-dependent motility of organelles
Whitehead Institute for Biomedical Research
Appointed in 2000
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Whitehead Institute for Biomedical Research
Appointed in 2000
Induction of mammary tumor by p-53-deficient stroma
National Institutes of Health
Appointed in 1955
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National Institutes of Health
Appointed in 1955
Formation and metabolism of nucleoside pholyphosphate
Stanford University
Appointed in 2011
A search for determinants of synaptic size and function
Columbia University
Appointed in 1986
Genetic control of recombination in yeast
Harvard University
Appointed in 2018
Superresolution imaging of age related changes to the neuronal cytoskeleton
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.
Sloan Kettering Institute for Cancer Research
Appointed in 2004
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Sloan Kettering Institute for Cancer Research
Appointed in 2004
Genetic approaches to primordial germ cell migration
Brigham and Women's Hospital
Appointed in 2007
Awarded Sponsor: Brigham and Women's Hospital
Polarity and pathogenesis: identification and characterization of cell polarity determinants in Vibrio cholerae
Albert Einstein College of Medicine
Appointed in 1973
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Albert Einstein College of Medicine
Appointed in 1973
Yeast mitochondrial nucleic acid metabolism
Columbia University
Appointed in 1996
Meiotic DNA synthesis and control of meiosis in yeast
University of California, Berkeley
Appointed in 2004
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University of California, Berkeley
Appointed in 2004
DNA pol III holoenzyme structure determination
Stanford University
Appointed in 1974
Isolation and characterization of integrated SV40 DNA
University of California, Berkeley
Appointed in 1969
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University of California, Berkeley
Appointed in 1969
Structure and function of histidine decarboxylase
Stanford University
Appointed in 1999
Micromechanics of kinesin movement
MRC Center, University Medical School, England
Appointed in 1975
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MRC Center, University Medical School, England
Appointed in 1975
Localization of chemical sites in biological electron microscopy
Harvard University Medical School
Appointed in 2003
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Harvard University Medical School
Appointed in 2003
Regulation of kinetechore assembly
University of California, San Francisco
Appointed in 2020
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University of California, San Francisco
Appointed in 2020
Principles of cellular behavior: gait coordination in unicellular walker
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.
Imperial Cancer Research Fund Laboratories, England
Appointed in 1986
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Imperial Cancer Research Fund Laboratories, England
Appointed in 1986
DNA ligase 1
Fred Hutchinson Cancer Center
Appointed in 1983
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Fred Hutchinson Cancer Center
Appointed in 1983
Fine mapping the hypersensitive sites in globin genes
Massachusetts Institute of Technology
Appointed in 1950
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Massachusetts Institute of Technology
Appointed in 1950
Cellular ultrastructure and function
University of Edinburgh, Scotland
Appointed in 1981
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University of Edinburgh, Scotland
Appointed in 1981
Isolation of the gene polycomb of Drosophila
University of California, San Francisco
Appointed in 1985
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University of California, San Francisco
Appointed in 1985
Structure/function analysis of the SRP receptor
University of California, San Francisco
Appointed in 2020
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University of California, San Francisco
Appointed in 2020
Dynamic control of the integrated stress response by elF2B
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.
University of Cambridge, England
Appointed in 1999
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University of Cambridge, England
Appointed in 1999
Protein-protein interactions in cell cycle regulation
Harvard University
Appointed in 2020
Characertization of catechol dehydroxyglases in the gut microbiome
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.
Boston Children's Hospital
Appointed in 2011
The role of secreted mircroRNA's in breast cancer metastasis
California Institute of Technology
Appointed in 2002
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California Institute of Technology
Appointed in 2002
Role of Mrg receptors in perception of pain
Rockefeller University
Appointed in 2002
E cadherin function in epidermal cell adhesion
Yale University /
Columbia University
Appointed in 1946
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Yale University / Columbia University
Appointed in 1946
Genetic aspects of growth
University of Colorado, Boulder
Appointed in 2021
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University of Colorado, Boulder
Appointed in 2021
Exploring the pangenome of Escherichia coli uncovers novel defense Mechanisms
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.
University of Stockholm, Sweden
Appointed in 1963
Mechanism of energy conservation in mitochondria
Rockefeller University
Appointed in 2004
Structural study of toxin-VG k+ channel complex
University of Illinois at Urbana-Champaign
Appointed in 2007
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University of Illinois at Urbana-Champaign
Appointed in 2007
A single molecular study of the exosome to understand the RNA 3'-5" processing, degradation, and polymerization
Yale University /
University of Texas Southwestern Medical Center
Appointed in 2008
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Yale University / University of Texas Southwestern Medical Center
Appointed in 2008
Mechanism for translational regulation of HMG CoA reductase
I am trying to figure out what an Argonaut-like protein is doing in the mitochondrion of the sleeping sickness parasite, Trypanosoma brucei.
I did my graduate work at the Johns Hopkins School of Medicine, in the Department of Biological Chemistry, where I worked on trypanosome fatty acid synthesis.  Protozoan parasites that cause human disease—i.e. malaria, Chagas disease, leishmaniasis, and sleeping sickness—are not only relevant medically, but often have surprising and unusual biologies that fill pieces of the larger picture of our own evolution.  For example, GPI anchors were first discovered in T. brucei and have a specific role in parasite evasion of the host immune system.  Besides my fascination with the biology of the bizarre, I enjoy living in New Haven with my dog Jack.
Rockefeller University
Appointed in 2016
Structural and mechanistic principles of the HCN pacemaker channel