Directory

Emily Bayer Jane Coffin Childs Fellow

University of Basel, Switzerland
Appointed in 2020

Sponsor: Alex Schier

Intuitively, humans seem aware of the fact that visceral sensations are related to their emotional or stress perceptions of the world. English idioms such as the heart “leaping” reflect excitement, the heart “sinking” reflects despair, and “gut feelings” reflect intuition. This conscious awareness of the reactions of the viscera suggests a two-way relationship between perception of the body and reaction of the brain, but the biological underpinnings and relevant neural circuits are still understudied._x000D_
_x000D_
The zebrafish has the great advantage of external fertilization and optical accessibility during development, which I will utilize to study how sensory inputs from the body shape brain state and activity. I hope to understand the kinds of sensory information transmitted from the body to the brain, and the ways that this affects how the brain generates behaviors._x000D_

Gwendolyn Beacham, Ph.D. Jane Coffin Childs Fellow

Boston University
Appointed in 2023

Sponsor: Dr. Elliott Hagedorn and Dr. Christopher Chen

The vascular system transports blood and immune cells throughout the body. Yet, how these cells selectively cross the endothelium and enter the appropriate cellular tissues is unclear. Dr. Gwendolyn Beacham will explore the fundamental mechanisms underlying this endothelial transmigration in Dr. Elliott Hagedorn’s and Dr. Christopher Chen’s labs at Boston University. Beacham predicts that endocytosis is important for this process and has identified candidate proteins by investigating blood stem cells. She will use zebrafish as a model system to validate her preliminary findings. Then, Beacham will use this understanding to engineer blood vessels with controllable endothelial transmigration in zebrafish and in human cell culture. This research may help improve the efficiencies of cancer therapies that rely on endothelial transmigration, such as bone marrow transplants and engineered CAR T-cells.

As a Ph.D. student in Dr. Gunther Hollopeter’s lab at Cornell University, Beacham investigated clathrin-mediated endocytosis. In particular, she discovered that endocytosis is inactivated via phosphorylation of the clathrin Adaptor Protein 2. These findings revealed a novel regulatory mechanism for endocytosis and set up Dr. Beacham to explore how endocytosis contributes to endothelial transmigration.

Brittany Belin Jane Coffin Childs - Simons Foundation Fellow

California Institute of Technology
Appointed in 2015

Sponsor: Dianne Newman

A native of rural Pennsylvania, my interest in biology was sparked by a summer research program for high school students on ribosome biogenesis at Carnegie Mellon University. As an undergraduate, I studied biochemistry and philosophy at the University of Notre Dame, where I researched the molecular evolution of bacterial actin-like proteins with Dr. Holly Goodson. I continued my Westward migration to pursue a PhD at UCSF. In my thesis research with Dr. Dyche Mullins, I developed new tools for in vivo imaging of nuclear actin, which I used to discover a role for nuclear actin filaments in the DNA damage response.

As a postdoc I decided to jump across the branches of the tree of life, and I am currently working in the lab of Dr. Dianne Newman at Caltech to determine how the membrane composition of rhizobia, soil bacteria that engage in symbiotic nitrogen fixation in the roots of legume plants, affects their symbiotic fitness and recognition by plant hosts. I am particularly interested in the role of hopanoid lipids, which may be required for bacterial adaptations to environmental stress.

Blair Benham-Pyle Jane Coffin Childs Fellow

Stowers Institute for Medical Research
Appointed in 2017

Sponsor: Alejandro Sanchez-Alvarado

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.

Tessa Bertozzi, Ph.D. Jane Coffin Childs - HHMI Fellow

Whitehead Institute for Biomedical Research
Appointed in 2021

Sponsor: Jonathan Weissman

Chemical modifications to DNA and histones are implicated in the establishment of heritable cell type-specific transcriptional networks. The emergence of molecular epigenetic editors creates new opportunities to mechanistically probe these relationships and understand the functional repercussions of epigenetic dysregulation in cancer and aging. The CRISPRoff editor was developed in a collaboration between the Weissman and Gilbert labs as a single fusion protein containing the catalytically inactive dCas9, a repressive KRAB domain, and DNA methyltransferase domains. Transient expression of RNA-guided CRISPRoff achieves robust and heritable gene silencing in human cells, likely as a product of the synergistic spatiotemporal relationship between the coupled domains. Using a CRISPR-based screening approach, I plan to uncover and mechanistically characterize additional cooperative protein interactions which facilitate the establishment and maintenance of long-term transcriptional memory.

Michael T. Bethune Jane Coffin Childs Fellow

California Institute of Technology
Appointed in 2010

Sponsor: David Baltimore

My research aims to identify prostate cancer-reactive T cell receptors and their cognate antigens, thereby enabling the design of novel TCR gene therapies and dendritic cell-targeted vaccines.  I am also using protein engineering to improve the safety and efficacy of T cell receptors in such therapies and to extend these therapies to other widely-prevalent cancers of epithelial origin.

My training began at the University of California, Davis, where I was introduced to biochemistry by my undergraduate mentor, Robert Fairclough.  After UC Davis, I spent two years in Washington D.C. before joining the Stanford Biochemistry Department as a graduate student.  There, I worked with my advisor, Chaitan Khosla, on celiac sprue, an autoimmune-like disease in which dietary gluten precipitates an inflammatory immune response in susceptible individuals.  This research piqued my interest in how immune responses are shaped by foreign material, and in the potential for using bacterial and viral vectors to augment immunity to pathogens and to mitigate autoimmunity.  As a deleterious self pathogen, cancer is a uniquely challenging target of this engineering immunity approach. When not working, I enjoy discovering new activities in the L.A. area with my wife, Carol San, who is an occupational therapist.

Marco Bezzi Jane Coffin Childs Fellow

Beth Israel Deaconess Medical Center
Appointed in 2015

Sponsor: Pier Paolo Pandolfi

The tremendous advances in DNA and RNA sequencing technologies have recently had a profound impact on our understanding of cancer biology and have revealed the importance of the non-protein-coding RNA molecular “space”. Disregarded for the past 20 years and considered products of aberrant RNA splicing, circular RNAs are nowadays acknowledged as an attractive type of noncoding RNA, probably involved in a multitude of cellular processes and able to play a critical role in human diseases._x000D_
_x000D_
The aim of my project is to uncover circular RNAs with diagnostic, prognostic and therapeutic potential in prostate cancer which represents the most common non-cutaneous malignancy and one of the leading causes of cancer-related deaths among men, both in Europe and in the United States. At the same time we aim to elucidate critical properties of this fascinating class of RNAs, opening new horizons for the entire cancer research field.

Manasi Bhate Jane Coffin Childs - HHMI Fellow

University of California, San Francisco
Appointed in 2013

Sponsor: William DeGrado

I am broadly interested in the structure, function and dynamics of proteins that mediate signal transduction across the cellular membrane. These include membrane receptors, enzymes, ion channels and transporters. Since signaling is a dynamic process we need to study the ensemble of protein conformations and motions to understand how physical and chemical stimuli are converted into cellular information.

My graduate training was in solid-state NMR of membrane proteins. I currently use a combination of NMR, protein engineering and biophysics to gain quantitative insights into a family of transmembrane kinases that allow bacteria to sense and adapt to antibiotics in their environment.

Email: Manasi.Bhate@ucsf.edu
Personal Website : https://sites.google.com/site/manasibhate/?

Sandhya Bhatia, Ph.D. Jane Coffin Childs - HHMI Fellow

University of Texas Southwestern Medical Center
Appointed in 2022

Sponsor: Michael K Rosen

Biomolecular Condensates are defined foci found in cells that have selectively concentrated biomolecules. The formation of biomolecular condensates via liquid-liquid phase separation, involving multivalent interactions among biomolecules, has emerged as an important principle for the organization of cellular structure and biochemistry. The molecular underpinnings governing the macroscopic behavior of multi-component condensates, formed by modular protein domains, remain poorly understood. There is limited understanding of how inter-domain binding affinities affect condensate energetics and dynamics, and whether the energetic behaviors can be inferred from known evolutionary relationships between the molecules. Studying these requires quantitative mapping of a phase diagram, which is a two-dimensional array of points for a two-component system and extends to being n-dimensional for n-components. The traditional methods used for mapping phase diagrams require substantial amounts of reagents and are labor-intensive. Hence, I have developed a high-throughput microfluidics-based platform in which hundreds of thousands of pL volume droplets can be made and analyzed as individual reaction chambers in a single experiment, enabling dense sampling of even high-dimensional phase spaces. With this method, I will be mapping phase diagrams and condensate dynamics for systems of increasing complexity. The characterization of the energetics of phase separation with a dataset of unprecedented scale will help in understanding (and eventually predicting) the behaviors of condensates from knowledge of the interactions and co-evolution of individual molecules.

Amir Bitran, Ph.D. Jane Coffin Childs Fellow

University of California, Berkeley
Appointed in 2022

Sponsor: Dr. Susan Marqusee

The majority of functions we associate with living thing are made possible thanks to the molecular functions of proteins. Proteins, just like cars and other macroscopic machines, require a specific 3D structure in order to be able to perform their functions and improper protein folding is linked to diseases cut as Alzheimer’s, Parkinson’s, and various cancers.  Yet despite decades of research, we still do not understand how proteins fold up into these structures, and what determines whether folding ultimately proceeds correctly—these questions are not addressed by structure-prediction algorithms such as DeepMind’s AlphaFold. It is crucial that we make progress on these issues if we are to rationally design treatments for misfolding diseases, and to predict evolution of organisms, which is often mediated by changes to protein folding and function.

All proteins are made up of one or more chains of amino acids. For some proteins, the physical and chemical interactions between these amino acids are entirely sufficient to drive protein folding into correct native structure.  But growing evidence suggests that, for many other proteins, these interactions instead cause the amino acid chain to misfold into non-functional molecular structures.  A major goal of my research is to understand how this conundrum is resolved in the complex cellular environment.

One possible resolution to this issue may lie in the fact that, in addition to folding, a protein molecule needs to be synthesized one amino acid at a time by the ribosome. It turns out that many proteins can start folding as they are being synthesized, a process known as co-translational folding which has been shown to significantly increase the odds that certain proteins fold correctly. Indeed, many proteins contain evolutionarily conserved slowdowns in their rate of synthesis at chain lengths corresponding to putative co-translational folding intermediates, indicating it is broadly useful to modulate synthesis rates to give time for co-translational folding. This is akin to how dance (analogous to a chain’s folding) is closely linked to musical rhythm (how quickly amino acids are added)—I may have taken this analogy a bit too far and written a musical piece inspired by it (The Dance of the Nascent Chain).

My research aims to develop a detailed molecular picture of this process, and why it is beneficial to fold co-translationally for many proteins, by combining in vitro and in vivo experimental techniques, physics theory and atomistic simulations. In the future, this interdisciplinary pipeline can also be applied to investigate additional complex processes in the cell including mechanisms of misfolding in disease.

Joshua Black Jane Coffin Childs Fellow

Massachusetts General Hospital
Appointed in 2009

Sponsor: Jonathan Whetstine

I am studying how chromatin structure contributes to transcription, DNA replication, differentiation and maintaining genome stability.  My research is focused on how the JMJD2 family of histone tri-demethylases are involved in regulating these processes.

I received BS degrees in biology and chemistry/biochemistry from Worcester Polytechnic Institute, where I became interested in understanding how the expression of genes was controlled to coordinate differentiation and development.¬†¬† I received my PhD at UCLA where, in Michael Carey’s laboratory, I developed a reconstituted chromatin system to begin to elucidate the biochemical events required prior to gene transcription.¬† My research uncovered an interaction between the critically important Mediator co-activator complex and the chromatin regulator p300. In post-doctoral work in the laboratory of Jonathan Whetstine, I am studying how the JMJD2 family of histone tri-demethylases regulates chromatin structure and gene expression.¬† I have uncovered an important role for one of these enzymes, JMJD2A, in DNA replication and cell cycle progression.¬† Since these enzymes are amplified in numerous cancers and important for maintaining genomic stability, this work has potential to lead to new cancer therapies.

John Blair, Ph.D. Jane Coffin Childs Fellow

New York University
Appointed in 2021

Sponsor: Satija Rahul

Protein phosphorylation is a fundamental, dynamic process that can have drastic effects on cellular physiology. Mutations in kinases, the enzymes that phosphorylate other proteins, are often implicated in neurological disease. Understanding the context and consequences of protein phosphorylation in different cell types throughout neurodevelopment is imperative to developing new treatments as well as our basic understanding of cell biology. Recent technological developments permit the simultaneous quantification of protein levels, chromatin accessibility and gene expression from single cells (DOGMA-Seq). I am extending this technology to quantify both phosphorylated proteins and total proteins as well as chromatin accessibility and gene expression. I am applying this assay at discrete timepoints throughout in vitro neurodevelopment to reveal previously uncharacterized cell-type specific signaling patterns affecting gene expression and ultimately, cell fate decisions.