Current Fellows

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Lauren Aguado

Laboratory of Virology and Infectious Disease, The Rockefeller University

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Entering the unknown: How do viruses transition to new hosts?

Gregory Allen

Department of Cellular and Molecular Pharmacology, University of California San Francisco

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Synthetic control of immune cell traffiking

Andrew Anzalone HHMI Fellow

Department of Chemical Biology and Therapeutics Science, Broad Institute/MIT/Harvard

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Genome editing with single nucleotide precision

Amjad Askary HHMI Fellow

Department of Biological Engineering, California Institute of Technology

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Dynamics of cell state transitions in early mammalian development

Synthetic recording of cell state trajectories during development

The incredible journey from a zygote to an animal entails transition of cells from one state to another as they proliferate. Although fundamental to our understanding of development, the trajectories of single cells during these transitions have been elusive due to technical limitations. A growing body of evidence suggests that cellular heterogeneity is prevalent in biological systems. Therefore, the average behavior of cell populations cannot be reliably used to infer the trajectories of the cells they comprise. Cellular behaviors are also highly dynamic. Techniques that rely only on static snapshots lose critical information about the longitudinal dynamics and spatial context of cells.

I am interested in developing methods for recording lineage and transcriptional event histories within the genome of the cells. Recently, our group has published a CRISPR/Cas9-based method, called MEMOIR, which involves “writing” of structured mutations at defined sites in the genome, where they can be read out using multiplexed in situ hybridization. Approaches analogous to phylogenetic inference can then be used to reconstruct lineage and event histories based on the mutation patterns. I seek to improve this system and implement it in mouse embryos to study dynamics of cell state transitions in early mammalian development. This work will provide the tools and theoretical basis for reconstructing lineage trees and decorating them with dynamic gene expression information, in virtually any developmental context.

Ling Bai

Department of Physiology, University of California San Francisco

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Identification of homeostatic signals that regulate AgRP "hunger" neurons

Steven Baker

Department of Neurological Sciences, Stanford University

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A comparative genomic analysis of lifespan evolution in verterbrates

Aging can be viewed as the time-dependent decline in organismal function which increases the likelihood of death. How and why we age remains one of the greatest mysteries in modern biology. Interestingly, the rate of aging–and ultimately lifespan of organisms–varies greatly even within vertebrates. Among extant vertebrates, extreme longevity appears to have arisen multiple times independently, suggestive of convergent evolution. My project aims to uncover the genes and pathways that contribute to lifespan variation using comparative genomics. At present over 100 vertebrate genomes have been sequenced and are publically available. Included among these organisms are species with both remarkably short and long lifespans. I have set out to develop a computational pipeline which identifies regions that exhibit molecular convergence within the genome of species sharing a similar lifespan. I then plan to characterize these regions biochemically to determine their effects on expression, regulation, and function of the involved genes. Longer term, I will develop mutant mice harboring variants with significant effects on function to directly assess their influence on lifespan in a well-studied model of vertebrate aging.

Karl Barber

Department of Genetics, Brigham and Women's Hospital

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dCas9-mediated assembly of protein microarrays for viral diagnosis

Michel Becuwe

Department of Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts

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Mechanisms of lipid droplet formation, with Robert Farese

Nathan Belliveau HHMI Fellow

Department of Biology, University of Washington

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Functional genomics of directed 3D cell migration

Blair Benham-Pyle

Stowers Institute for Medical Research

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Cell fate and intercellular signaling in planarian regenerative organizers

The growth and regeneration of adult tissues requires the establishment of local signals that regulate growth and differentiation. While signaling molecules regulating proliferation have been studied in a wide range of tissue and disease contexts, mechanisms linking tissue composition and cellular cooperativity to growth and regenerative potential are poorly understood. During development, signaling centers with a defined genetic signature – organizers – induce the proliferation, migration, and differentiation of neighboring cells and establish patterns critical for the formation of adult organ systems. However, it is unclear if comparable signaling centers regulate tumor development or regeneration. The planarian worm provides a unique opportunity to study the establishment and function of regenerative signaling centers in vivo due to its extraordinary ability to regenerate organ systems from tiny fragments in approximately one week.


As a postdoctoral fellow in the Sanchéz laboratory at the Stowers Institute for Medical Research, I plan to use a combination of sequencing and quantitative imaging techniques to identify the minimal cell types and tissue structures required for complete regeneration and accurate scaling of planarian worms. This work is expected to reveal novel mechanisms regulating self-organization and growth in resource-limited adult tissues and may expand our ability to improve human regenerative capacity and treat human cancers that arise from aging tissues.

Julianna Bozler

Department of Cell and Developmental Biology, University of Pennsylvania

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Molecular regulation of behavioral and reproductive plasticity in ants

Peter Bruno HHMI Fellow

Department of Medicine, Brigham and Women's Hospital

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The role of ZNF292 in senescence and tumorigenesis

Senescence is an irreversible cell state characterized by permanent exit from the cell cycle that occurs in response to cellular stresses such as shortened telomeres and DNA damage.  Thus, senescent cells accumulate as an organism ages and are thought to contribute to the gradual decline in tissue function as we age.  Importantly, elimination of senescent cells in old mice extends healthy lifespan.  Therefore, achieving a better understanding of the genetic underpinnings of senescence can lead to improved prevention and treatment of aging-related diseases.

It is currently thought that senescence is mediated by three distinct pathways, characterized by their primary facilitators: p53, p16 and GATA4. However, there are likely many more factors that are critical to senescence induction. Thus, we conducted a whole genome CRISPR screen for genes necessary for replicative senescence in IMR90 primary fibroblasts. One novel gene identified was ZNF292.  Thus, the objective of my postdoctoral work is to gain a more thorough understanding of the role of ZNF292 in senescence and tumorigenesis.



Cori Cahoon

Department of Biology, Institute of Molecular Biology, University of Oregon, Eugene

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Defining mechanisms of heat-sensitive synaptonemal complex in spermatocytes

Pau Castel

Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco

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Novel effectors of oncogenic KRAS that regulate cell signaling


RAS proteins are small GTPases that act as GDP/GTP-regulated switches and play an essential role in signal transduction, proliferation, and survival. Activating mutations in the different RAS isoforms (KRAS, HRAS, and NRAS) are found in several human pathologies, including cancer and developmental syndromes, such as Noonan and cardio-facio-cutaneous syndromes. Efforts in the field of chemistry have been made in order to target these oncogenic GTPases and recent discoveries have provided the first compounds capable to target KRAS directly. Using these chemical probes, mass spectrometry, and additional genetic strategies, I study the role of novel downstream effectors of activated GTP-bound RAS oncoproteins.


Identification of such molecular effectors will shed light into the mechanisms of pathogenesis of RAS oncoproteins and could also be used as an alternative way of therapeutically target the RAS pathway.


Zhao Chen HHMI Fellow

Laboratory of Molecular Neurobiology and Biophysics, The Rockefeller University

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Mechanisms of ATP-sensitive potassium, (KATP) channel gating

ATP-sensitive potassium channel (KATP) is an ion channel gated by ATP and ADP, and by doing so, it translates the metabolic state of a cell into electric signals. At molecular level, KATP is endowed with sensitivity to ATP and ADP through direct interactions with multiple binding sites. These binding sites are scattered across the entire KATP molecule, which is a tetramer of hetero-dimers that are composed of a type of inward rectifier potassium ion channel (Kir) and an ABC transporter (SUR).Previous studies have identified an inhibitory site on Kir that results in channel closure upon binding to ATP, and stimulatory sites on SUR that favor channel opening when occupied by either MgADP or MgATP. These observations pose a puzzle because in healthy cells ATP exists at millimolar concentrations whereas ADP is present only in the ten micromolar range. How then does KATP detect changes in ADP concentration when the background ATP concentration remains so high that ATP inhibition should dominate? To answer this question, we have to determine what the ATP and ADP affinities are at their respective sites and also understand how occupancy of these sites allosterically regulate the pore’s gate. Once this level of understanding is reached we can then try to predict the response of KATP to different metabolic states. Finally, we can integrate these responses into the broader signaling network that involves other closely related partners to describe the action of KATP at a systems biology level. My project in the MacKinnon lab aims to address this problem using a combination of electrophysiology and structural biology techniques.

Thomas Cooke HHMI Fellow

Whithead Institute for Biomedical Research

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The origin and evolution of cell types

Eric Dang Merck Fellow

Department of Biophysics and Biochemistry, University of California, San Francisco

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Uncovering the molecular drivers of lethal invasive fungal infection

Hai Dao

Department of Chemistry, Princeton University

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Defining the interactome of the acidic patch with chromatin effectors

Recent studies have revealed the nucleosome acidic patch as a nexus for chromatin interacting proteins. Understanding the regulation underlying these binding events is critical to understanding of how genetic material is packaged and accessed in eukaryotes and how misregulation can lead to disease. It is well established that post-translational modifications (PTMs) of the histone tails help choreograph biochemical outputs on chromatin. By contrast, much less is known about how PTMs regulate access to the acidic patch, even though several modifications are proximal to this region. My research will combine the specificity of diazirine-based photocrosslinking reaction with high-throughput mass spectrometry-based techniques to accelerate the investigations into these regulations. The applications will be showcased in ascertaining the binding site between chromatin-remodeling proteins and the acidic patch, and a large-scale study to define the interactome of the acidic patch and chromatin effectors as the function of PTMs.

Alicia Darnell Merck & Co., Fellow

Koch Institute, Massachusetts Institute of Technology

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Understanding cellular and organismal amino acid homeostasis

Rui Dong

Department of Cellular and Molecular Pharmacology, University of California, San Francisco

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Probe the interplay between actin cytoskeleton and immunoreceptor signaling

Seth Donoughe

Department of Molecular Genetics and Cell Biology, University of Chicago

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Dissecting mechanical feedback in the Drosophila egg chamber

Vinay Eapen

Department of Cell Biology, Harvard Medical School

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Systemic analysis of the mammalian selective autophagy cargo network

The 2016 Nobel laureate Dr. Yoshinori Ohsumi remarked, “ Life is an equilibrium state between the synthesis and degradation of proteins”. My research focuses on Autophagy, a process whereby proteins are marked for destruction in cells by the lysosome. I became interested in autophagy during my PhD in Dr. Jim Haber’s lab at Brandeis University, and have been hooked on it ever since!

The autophagy-lysosome system targets the degradation of a specific cohort of proteins via “selective autophagy”. The dysfunction of this phenomenon has been linked to a myriad of human disorders. We have only scratched the surface of the known targets of this fascinating biological process. Under the guidance of my mentors, the aim of my research will be to comprehensively catalog the list of selective autophagy substrates by employing quantitative mass spectrometry of the autophagy-lysosome system. An overarching goal of my research is to obtain knowledge of the selective autophagic targets in cancer, which may present opportunities for the specific targeting of this process

I grew up in New Delhi, India.  After completing my undergrad program in Biotechnology at the Vellore Institute of Technology in South India, I moved to the U.S.  (Brandeis university, MA)  for graduate studies.  In my spare time, I am whittling down all of the 48 four thousand feet peaks in the White Mountain range while assiduously taking guitar lessons in the hope of one day playing lead guitar for a major rock band.

Julius Enghlebreth-Holm Grantee - Jane Coffin Childs Fund

University of Copenhagen, Denmark, Institute of Pathology

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Priscilla Erickson

Department of Biology, University of Virginia

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Genetics and evolution of photoperiodism in Drosophila melanogaster

Organisms exhibit diverse strategies to survive environments that vary in space and time. In temperate climates, environmental cues are used to anticipate the onset of unfavorable seasons. One of the most reliable indicators of season is photoperiod: the length of light and dark periods within a 24-hour day. Insects exhibit a spectacular array of responses to changes in season. For example, aphids develop sexually reproducing morphs in the fall, moths and lacewings develop unique seasonal patterns and colors, monarch butterflies undergo seasonal migrations, and hundreds of species, including the fruit fly Drosophila melanogaster, are able to suspend development or reproduction until more favorable conditions return. Despite nearly a century of research on insect seasonality and photoperiodism, the genetic pathways used to make these ecologically crucial transitions remain unknown. The abundance of genetic and genomic resources for Drosophila makes it an ideal study system for this question.

My research uses custom-built environmental chambers, field studies in an experimental orchard, and novel genetic mapping techniques to dissect the genetic basis of photoperiodism and seasonal responses in Drosophila. Understanding how insects detect photoperiod will inform our understanding of economically and biomedically important insects and offer predictions about how insects may adapt to ongoing anthropogenic climate warming in which temperature, but not photoperiod, is changing.

Monifa Fahie

Department of Biology, Brandeis University

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Translation regulation and viral exploitation in innate immunity

Qing Feng

Department of Cell Biology, Harvard Medical School

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Mechanistic dissection on nonsense-mediated decay

Anthony Flamier

Whitehead Institute for Biomedical Research

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Formation of phase separated condensated in fragile X-linked syndromes

Christina Gladkova HHMI Fellow

Department of Cellular and Molecular Pharmacology, University of California, San Francisco

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Understanding mitochondrial trafficking: linking mitochondria to motors

Daniel Goodman

Hormone Institute and Diabetes Center, University of California San Francisco

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Mapping and manipulating T-cell plasticity via synthetic receptor libraries

Immune dysregulation is implicated in a variety of diseases, and modulation of immune cell signaling has shown remarkable promise in the treatment of allergy, autoimmunity, and cancer. At the surface of each immune cell, hundreds of different receptors serve as the gateways through which information is recognized and integrated. These receptors are surprisingly modular and can be mutated and composed to rewire cellular inputs and outputs, as showcased by the success of cell-based genetic therapies like Chimeric Antigen Receptor T-cell (CAR-T) therapy.


My work combines computational protein design, chemical DNA library synthesis, and high-throughput pooled screening of millions of genetically modified primary human immune cells, each with different synthetic receptors. We are measuring these cells for differences in proliferation, differentiation, activation, and localization, both in vitro and in animal models. A better understanding of the relationship between receptor sequence, signaling outcome, and cellular phenotype will lead to next-generation cell-based genetic therapies which manipulate the immune system to combat a variety of diseases.


Yogesh Goyal

Department of Bioengineering, University of Pennsylvania

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Cellular states guiding plasticity and reprogramming paradigms in cancer

Thomas Graham Merck Fellow

Department of Molecular and Cell Biology, University of California, Berkeley

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In-Vivo single-molecule imaging of enhancer-promoter communication

The different cell types in our body have an incredible variety of sizes, shapes, and functions, despite having the same genome. Differences between cell types arise from differences in which genes are transcribed into RNA. Transcription is regulated by DNA sequences called enhancers, which in some cases are located hundreds of thousands of basepairs away from their target genes. While we know the identities of many of these enhancers, and the proteins that bind to them, we lack a coherent model of how enhancers regulate transcription. Various lines of evidence suggest that large protein complexes form a bridge between enhancers and their target promoters. However, we lack a basic understanding of the composition, size, and internal organization of these enhancer-promoter complexes. Important questions are: 1) How many copies of different proteins assemble at enhancers and promoters? 2) What protein-protein and protein-DNA interactions are important for assembling enhancer-promoter complexes? 3) How dynamic are these complexes? 4) How do enhancer-promoter complexes ultimately regulate transcription? To address these questions, I am working to develop new fluorescence imaging approaches in live cells, which will combine fluorescent labeling of DNA, RNA, and protein with new technologies such as single-molecule tracking and lattice light sheet microscopy.

Abigail Groff

Whitehead Institute for Biomedical Research

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Sexually dimorphic gene expression in human preimplantation development

Joshua Gruber

Department of Genetics, Stanford University, Stanford, California

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Integrated omics of malignant transformation by breast cancer genes, with Michael Snyder

Through my clinical work with oncology patients I became acutely aware of how few interventions we are able to offer patients to prevent cancer.  Even patients with inherited syndromes that confer a near-certainty of developing cancer have few, often unappealing, options to actually prevent cancer.  This motivated me to investigate molecular mechanisms of the earliest steps of malignant transformation.  I chose to study the genes causing inherited breast cancer because each one constrains the malignant phenotype of breast cells, an effect that can be modeled in vitro.

These ideas led me to team up with my advisor Dr. Michael Snyder at Stanford who has pioneered multiple high-throughput omics technologies to densely profile biological systems.  These tools allow for an unprecedented window into cellular dynamics driving malignant transformation.  I am particularly interested in how genomic aberrations in non-coding DNA elements can unlock transcriptional programs that drive malignancy.  The hope is to uncover molecular switches that can be targeted to prevent cancer onset.

Jennifer Hamilton

Department of Molecular and Cell Biology, University of California, Berkeley

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Redesigning lentiviruses to achieve CRISPR-Cas9 genome engineering in vivo

Whitney Henry

Whitehead Institute for Biomedical Research

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Targeting the EMT program in high grade serous ovarian cancer

High-grade serous ovarian cancer (HGSOC) is the most aggressive gynecological malignancy for which few targeted therapies exist. The poor prognosis associated with this disease underscores the importance of targeting critical determinants of tumor relapse and therapeutic resistance, which account for the high morbidity rate. Given our lab’s findings that acquisition of the epithelial-to-mesenchymal transition (EMT) endows carcinoma cells with enhanced tumor-initiating potential and therapeutic resistance, I propose to identify novel mechanisms to reverse the EMT program by performing a pooled CRISPR/Cas9-based screen using a genome-wide sgRNA library optimized for high target cleavage efficiency. Candidate hits will be functionally characterized to ascertain their role in EMT-associated phenotypes and the mechanism by which their depletion elicits a mesenchymal-to-epithelial transition (MET). Furthermore, I will investigate the potential translation of these findings for therapeutic utility by evaluating the efficacy of tumor-targeting Layer-by-layer (Lbl) nanoparticles that deliver siRNAs or drugs that induce an MET alone or in combination with platinum-based drugs using clinically relevant HGSOC patient-derived xenograft mouse models and genetically engineered mouse models.


Theodore Ho HHMI Fellow

Department of Bioengineering, Stanford University

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The role of altered neural activity in brain aging and cognitive decline

Aaron Hosios

Department of Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health

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Role of the P13K-mTOR signaling network in reprogramming lipid metabolism

Melissa Hoyer

Department of Cell Biology, Harvard Medical School

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Spatial and temporal organelle quality control during changes in cell state

Wenyan Jiang Simons Foundation Fellow

Department of Systems Biology, Columbia University

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Microbial adaptation to extreme environments facilitated by CRISP-Cas

Nicholas Jourjine

Department of Molecular and Cellular Biology, Harvard University

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Genetic and neural basis of natural variation in infant vocalization

Infant vocalization is a pervasive mammalian social behavior that elicits parental care essential for infant health. Features of infant vocalization are innate, heritable, and vary between species, but we know little about the genetic or neural mechanisms underlying this variation. To better understand these mechanisms, I study the cries of infant Peromyscus mice (also known as deer mice), a group of closely related rodents that have recently diversified across North America and evolved a range of heritable behaviors. Deer mice are attractive systems to understand natural variation in infant vocal behaviors because interfertile species exhibit infant cries that differ in their spectral and temporal features, opening the possibility to map the genetic basis of natural variation in these features. Using approaches from neuroscience, genetics, and ethology, my work aims to make explicit mechanistic links between genes, neurons and a conserved mammalian behavior essential for early life health in rodents and humans alike.

Roarke Kamber

Department of Genetics, Stanford University

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Mechanistic dissection of mTOR and autophagy gene function in phagocytosis

Maya Kasowski

Department of Pathology, Stanford University

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Variation in chromosomal interactions in 10 human poplulations

Justus Kebschull

Department of Biology, Stanford University

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Investigating cell type and brain circuit evolution in the cerebellum

Brain circuits and the neuronal cell types that form them are not static over evolutionary time. Rather, they cause and reflect the changing repertoire of animal behavior. How circuits and cell types change from their ancestral state to support novel behaviors during evolution, therefore, gives us important clues as to their current function. In my project, I will investigate the interaction between the cerebellum and the rest of the brain from this evolutionary angle by studying the progressive expansion and elaboration of the deep cerebellar nuclei, the output pathway of the cerebellum. I will profile transcriptional and projectional cell types of the DCN across species to probe changes in the DCN over deep evolutionary time. I will then integrate this dataset with developmental trajectories of the identified cell types in mouse, to provide mechanistic insight into how brain regions specialize on the level of single cells and circuit wiring to support new functions over the course of evolution.

Mina Kojima

Department of Genetics, Yale University

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Dissecting the molecular mechanisms that trigger zygotic genome activation

Dhivya Kumar

Department of Biochemistry and Biophysics, University of California, San Francisco

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Centriolar satellites use phase separation to remodel the centrosome

Naina Kurup

Department of Chemistry and Chemical Biology, Harvard University

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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.

Jette Lengefeld HHMI Fellow

Department of Biology, Koch Institute Massachusetts Institute of Technology

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Stem cell division and aging

Jaechul Lim

Department of Immunobiology, Yale University

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Deciphering the mechanism and significance of stress tolerance

Ding Liu HHMI Fellow

Department of Molecular and Cellular Biology, Harvard University

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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

Department of Biology and Biological Engineering, California Institute of Technology

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In vivo structure and function of the H. pylori cag type IV secretion system

Nadja Makki

Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco

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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’s lab at Stanford to study the connectivity of individual neurons in the brain. For my current postdoc in Dr. Nadav Ahituv’s 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.

Prerna Malaney

Department of Leukemia, MD Anderson Cancer Center

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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.

Joshua Meisel Merck & Company

Department of Molecular Biology, Massachusetts General Hospital

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Molecualr mechanisms of oxygen sensation and mitochondrial dysfuntion

Molecular oxygen presents a fundamental biological problem: it is vital for life, yet also incredibly toxic. As the terminal electron acceptor in aerobic respiration and the redox engine of mitochondria, oxygen provides eukaryotes with the vast majority of their energy. However when molecular oxygen is reduced it can form damaging reactive species, and recent work has demonstrated that animals with genetic lesions in the mitochondrial respiratory chain are extremely vulnerable to oxygen toxicity. How animals have evolved to manage this double-edged sword remains a fundamental question.
The biology and natural ecology of the nematode C. elegans make it an attractive system in which to study oxygen tolerance. Wild type C. elegans are tolerant of oxygen concentrations ranging from 1% to 100%, and years of genetic studies have generated a rich toolbox of mitochondrial mutants. I will use these mutants to study the biology of oxygen tolerance, which may simultaneously shed light on the connection between mitochondrial disease and oxygen toxicity.

Kailin Mesa HHMI Fellow

Skiball Institute of Biomolecular Medicine New York University Langone Health Center

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Uncovering the role of the inflammatory response in digit tip regneration

Several vertebrate species have the astonishing ability to regenerate their limbs following amputation. In mammals, including both mice and humans, this regenerative capability has been restricted to the digit tip. Both digit tip and complete limb regeneration follow a stereotypic process termed epimorphic regeneration where a population of progenitor cells, termed the blastema, form at the injury site to replace the multiple tissues lost (including blood vessels, nerves, bone, etc.). Several studies have demonstrated that macrophages are essential for epimorphic regeneration. However, it remains largely unknown how macrophages facilitate blastema rather than scar formation. Utilizing the mouse digit tip, which displays regenerative or scarring outcomes dependent on amputation site, we are functionally testing which immune cell types uniquely contribute to epimorphic regeneration. Furthermore, by combining diverse genetic tools with intravital imaging, we are beginning to understand how injury-induced inflammation yields a permissive tissue environment for epimorphic regeneration in mammals.

Tycho Mevissen HHMI Fellow

Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School

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Mechanism of transcription-coupled DNA interstrand cross-link repair

Jeffrey Morgan HHMI Fellow

Department of Biochemistry, University of Utah

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The eukaryotic RNA-metabolite interactome and its role in gene regulation

Frank Moss

Department of Biochemistry and Biophysics, University of California, San Francisco

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Structural studies of membrane fission and highly constricted membranes

Edwin D. Murphy Grantee - Jane Coffin Childs Fund

University of Tennessee, Department of Pathology

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James Nelson

Department of Chemical Biology and Therapeutic Sciences, Broad Institute

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Continual evolution of proteins in eukaryotes

Eugene L. Opie Grantee - Jane Coffin Childs Fund

The Rockefeller Institute

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Youcef Ouadah

Department of Biology & Biological Engineering

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A genetic approach to the logic and evolution of aggression circuitry

Samuel Pontes

Biological Sciences, Columbia University

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Behavioral function of pattern completion in the cortex

Jen Quick-Cleveland

Department of Molecular and Developmental Biology, University of California, Santa Cruz

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The impact of RNA polymerase II pausing on co-transcriptional splicing

RNA polymerase II (RNAPII) kinetics are well-known to influence splicing patterns. Recent evidence has revealed that many introns are spliced right after they are transcribed, opening the potential for cross-regulation between these two key processes. During transcription, RNAPII pauses during initiation and during 3’ end processing, and these pauses are thought to allow the recruitment of necessary protein factors. Although more transient, RNAPII also pauses throughout elongation, however the significance of these pauses is unclear. Importantly, many of these pauses occur near the exon-intron boundaries.

I am working to uncover the mechanisms that govern co-transcriptional splicing decisions. I am investigating the impact of RNAPII pausing on changes in splicing patterns using a short artificial arrest sequence, which allows me to engineer RNAPII pauses in any location. This DNA element, combined with improved genome-wide approaches such as Single Molecule Intron Tracking (SMIT), will allow me to assess how RNAPII pauses impact splicing patterns in both yeast and human cells.

Stephanie Ragland

Department of Pedicatrics, Boston Children's Hospital, Harvard Medical School

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Mechanisms of transport for bacterial molecules across phagosomal membranes

Kei Saotome HHMI Fellow

Integrative Structural and Computational Biology/Neuroscience, Scripps Research Institute

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Molecular structure and mechanism of Piezo mechanotransdution channels

Piezo proteins are ion channels that sense mechanical force in various physiological pathways, including touch sensation, breathing, and vascular development. Mutations in Piezo cause diseases associated with mechanotransduction defects, including distal arthrogryposis and dehydrated hereditary stomatocytosis. Piezos are unrelated to other known ion channels, and how they transduce mechanical force into channel opening remains unknown. As a joint postdoc in Andrew Ward and Ardem Patapoutian labs, I use cryo-electron microscopy and other biophysical approaches to gain a mechanistic understanding of Piezo function.”

Koning Shen

Department of Molecular and Cellular Biology, University of California Berkeley

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Defining the protective role of the mitochondrial stress response in aging

Niladri Sinha HHMI Fellow

Department of Molecualr Biology and Genetics, Johns Hopkins University School of Medicine

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Defining mechanisms for selective translation in ribosomopathies

Allen Su

Koch Institute, Massachusetts Institute of Technology

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Molecular basis of karyotype evolution in Ewing's sarcoma

Howard C. Taylor Jr. Grantee - Jane Coffin Childs Fund

Columbia University, Department of Obstetrics and Gynecology

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Kaloyan Tsanov

Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center

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The role of ribosomal protein gene deletions in liver cancer

Frederick Varn Merck & Co. Fellow

Department of Genomic Medicine, The Jackson Laboratory

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Glioma evolution in the presence of local immune activity

Owen H. Wangensteen Grantee - Jane Coffin Childs Fund

University of Minnesota, Department of Surgery

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Andrew Weems

Department of Bioinformatics, UT Southwestern Medical Center

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Bleb-nucleated signaling scaffolds in metastasis-prone melanoma cells

Aaron Whiteley

Department of Microbiology and Immunology, Harvard Medical School

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Identifying novel nucleotide second messengers from mammals using bacteria

Nucleotide second messengers are crucial for development and signaling in both humans and bacteria. Nucleotide-centric pathways in human cells are targets of therapeutic interventions for cancer and diabetes, but signal regulation is complex and remains poorly understood. My work reconstructs mammalian nucleotide signaling in bacterial systems, creating the transformative opportunity to leverage bacterial genetics to uncover how these pathways are mechanistically regulated. Future findings from this work will enhance our understanding of known and previously uncharacterized cell signals in eukaryotes and prokaryotes.

Prior to my postdoctoral work, I earned my Ph.D. in Daniel A. Portnoy’s Lab, at the University of California, Berkeley. There, I worked on essential genes and virulence regulation in the bacterial pathogen Listeria monocytogenes.

Gregory Wyant HHMI Fellow

Department of Medical Oncology, Dana-Farber Cancer Institute

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Unbiased analysis of the mitochondrial permeability transition pore

Helen H. Yang HHMI Fellow

Department of Neurobiology, Harvard Medical School

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Investigating the role of decending neurons in flexible motor control

Zepeng Yao

Department of Molecular and Cell Biology, University of California Berkeley

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Sensory integration of taste and smell in drosphila

Adam Yokom

California Institute for Quantitative Biosciences, University of California, Berkeley

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Mechanism of mTORC1 lysosomal recruitment via Rag:Ragulator

My current work focuses on understanding the molecular mechanism of mTORC1 activation and recruitment to the lysosome. Substrate phosphorylation by activated mTORC1 promotes cellular growth and inhibits catabolic pathways such as autophagy. The heptameric Rag:Ragulator complex in response to amino acids and growth factors binds and recruits mTORC1 to the lysosomal surface. Despite recent advancements in our understanding of the mTORC1 pathway, how this fundamental mTORC1:Rag:Ragulator complex forms is still poorly understood. Furthermore, a number of mutations have been identified within RagC for patients with follicular lymphoma which are thought to perturb this interaction hijacking the mTORC1 growth pathway. As a postdoctoral fellow in Hurley lab, my goal is to dissect the conformational states of mTORC1 throughout the activation pathway and capture the interaction with Rag:Ragulator

Coral Zhou

Department of Molecular and Cell Biology, University of California, Berkeley

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Uncovering molecular determinants of mitotic chromosome scaling

Our genomes are packaged into functional units of DNA called chromosomes, which are constantly being re-organized and re-shaped to match the demands of the cell. The most dramatic form of this reorganization happens as the cell prepares to divide: chromosomes are replicated, highly condensed, and aligned at center of the mitotic spindle, the complex protein-based machinery that physically separates exactly one copy of the genome to each daughter cell. Errors in this complex sequence of events can result in broken or rearranged chromosomes, known to be a significant source of mutations that drive the progression of many cancer types. A key factor in maintaining genome integrity during cell division is careful regulation of the length of the mitotic chromosome. In studies where chromosomes are artificially lengthened, the mitotic spindle fails at pulling the chromosomes apart, especially when certain cell cycle regulators are depleted. These results suggest that there are molecular pathways that can sense the physical dimensions of a chromosome and communicate this property to downstream regulators of the mitotic machinery. Yet, the exact dimensions being sensed and the molecules involved in this relay of information are still a mystery. Our goal is to identify the molecular pathways that sense, shape and re-enforce chromosome size during cell division. To do this, we will use the vertebrate model system Xenopus laevis, a powerful system for studying how physical dimensions of subcellular structures are determined during embryo development. Previous work from our lab has shown that mitotic chromosomes isolated from embryos in later stages of development are shorter compared to those isolated from early development. These results have provided a launching pad for our proposed work to now identify the molecular pathways that govern this change in size. We aim to (1) characterize how chromosomes are re-organized as they shrink, (2) find the molecules that contribute to these observed size changes and (3) implement the latest advances in imaging technology to test how changes in chromosome size affect embryo development. Because large-scale chromosome rearrangements are a driving force for many cancers, our findings will also provide a foundation for further research into how cancer cells hijack normal chromosome-size control pathways to continue growing and dividing. Also, since cellular behaviors during embryo development are very similar to those in a growing tumor, the tools we will develop to image chromosome dimensions in a growing embryo will greatly enhance our ability to visually assess large-scale chromosome rearrangements in cancer cells, both for research and diagnostics purposes.