Yale University
Appointed in 1995
University of California, San Diego
Appointed in 2005
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University of California, San Diego
Appointed in 2005
Stanford University
Appointed in 1981
Stanford University
Appointed in 1974
University of Colorado, Boulder
Appointed in 1999
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University of Colorado, Boulder
Appointed in 1999
California Institute of Technology
Appointed in 2021
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California Institute of Technology
Appointed in 2021
While cells are often studied in suspension or monolayers, more structured forms like tissues and biofilms dominate natural environments. In such settings, the concentrations of critical nutrients like sugars and O2 vary in space and time because cells produce and consume them locally, leading to measurable differences in physiology and gene expression between nearby cells. Spatially structured environments therefore represent many-body systems interacting on multiple timescales through a rich collection of chemical and physical processes. My overriding goal is to determine whether metabolism in mixed biofilms can be predicted quantitatively from simple models with intelligible and measurable parameters. I am currently developing Pseudomonas aeruginosa, a model bacterium that grows in suspension and as a biofilm, as a model for studying metabolic heterogeneity in spatially structured environments. It is commonly assumed that variation in the local O2 concentration is a primary determinant of metabolic heterogeneity in biofilms. As such, I am developing optical approaches to measure local O2 concentrations in real time to test whether a mathematical model can explain O2 dynamics, cell growth, and metabolic rates in biofilms.
Whitehead Institute for Biomedical Research
Appointed in 2019
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Whitehead Institute for Biomedical Research
Appointed in 2019
Stanford University
Appointed in 1967
Dana-Farber Cancer Institute /
Ludwig Institute for Cancer Research, La Jolla
Appointed in 1996
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Dana-Farber Cancer Institute / Ludwig Institute for Cancer Research, La Jolla
Appointed in 1996
Cornell University
Appointed in 1988
MRC Center, University Medical School, England
Appointed in 1985
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MRC Center, University Medical School, England
Appointed in 1985
Salk Institute for Biological Studies
Appointed in 1992
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Salk Institute for Biological Studies
Appointed in 1992
Yale University
Appointed in 1988
National Institutes of Health /
The Johns Hopkins University
Appointed in 1980
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National Institutes of Health / The Johns Hopkins University
Appointed in 1980
Oxford University, England /
Yale University
Appointed in 1982
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Oxford University, England / Yale University
Appointed in 1982
National Institutes of Health
Appointed in 1983
Carnegie Institute for Science
Appointed in 2007
University of California, San Francisco
Appointed in 1980
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University of California, San Francisco
Appointed in 1980
Massachusetts General Hospital
Appointed in 2000
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Massachusetts General Hospital
Appointed in 2000
Case Western Reserve University
Appointed in 1959
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Case Western Reserve University
Appointed in 1959
University of Michigan
Appointed in 1973
Stanford University
Appointed in 1981
Weizmann Institute of Science, Israel
Appointed in 1971
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Weizmann Institute of Science, Israel
Appointed in 1971
Stanford University School of Medicine
Appointed in 2012
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Stanford University School of Medicine
Appointed in 2012
Cambridge University, England
Appointed in 1952
Yale University
Appointed in 1971
Yale University
Appointed in 1986
University of California, Davis
Appointed in 2012
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University of California, Davis
Appointed in 2012
University of California, San Francisco
Appointed in 2005
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University of California, San Francisco
Appointed in 2005
Yale University School of Medicine
Appointed in 1985
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Yale University School of Medicine
Appointed in 1985
Massachusetts General Hospital
Appointed in 2023
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Massachusetts General Hospital
Appointed in 2023
Mitochondria generate energy needed to power cells and multicellular organisms. Wrinkles in the inner mitochondrial membrane, known as cristae, concentrate molecular motors for energy production. However, it is unclear how the wrinkly cristae are formed. Dr. Michelle Fry will use a clever approach to investigate cristae formation in cells. She will introduce candidate protein/protein complexes into parasitic protist mitochondria. These mitochondria are smooth, making them amenable for testing with proteins are sufficient to generate cristae. Dr. Fry will use advanced electron microscopy techniques to image changes in mitochondrial morphology. Fry will conduct these studies in Dr. Luke Chao’s lab at Massachusetts General Hospital. These experiments will provide fundamental insights into mitochondrial biology and may provide clues for mitochondrial pathological dysfunction.
As a graduate student in Dr. Bil Clemons lab at the California Institute of Technology, Fry used structural biology to study the targeting of membrane proteins to the endoplasmic reticulum. Specifically, Dr. Fry captured several structural conformations of a protein chaperone, Get3. Fry demonstrated how conformational flexibility is important for Get3 to integrate multiple regulatory signals (binding partners, client proteins, nucleotide binding and hydrolysis). Dr Fry is now excited to use cryo-electron tomography to capture the conformational landscape of proteins that regulate mitochondrial cristae formation in cells.
University of Washington
Appointed in 2024
Mitochondria are cellular organelles that house their own DNA. There are hundreds to thousands of copies of the mitochondrial genome (mtDNA) in each cell. Often, mtDNA copies are not the same; rather, a fraction of them carries mutations. Moreover, the composition of mtDNA varies drastically across cells and cell types. Mitochondrial diseases manifest when the pathogenic mutations reach a high percentage in a substantial fraction of cells. However, it is still unclear how mtDNA mutations expand and how cell-to-cell variation of mtDNA composition is formed.
Dr. Yi Fu will address these questions in Dr. Jay Shendure’s lab at the University of Washington. Dr. Fu will develop a method to accurately genotype mtDNA at single-cell resolution and employ this method to monitor mtDNA mutations during differentiation. Fu will also combine this approach with CRISPR perturbation to identify factors that impact the mitochondrial mutation burden in various cell types. These experiments will uncover cell type-specific regulation of mitochondrial genome maintenance. Furthermore, Fu’s research may provide insight into novel therapeutic approaches for mtDNA-associated diseases.
Fu’s expertise in mtDNA stems from her graduate studies in Dr. Agnel Sfeir’s lab at New York University and Memorial Sloan Kettering Cancer Center. There Fu discovered that double-strand breaks in mtDNA activate the integrated stress response, highlighting the cellular program to cope with defective mitochondrial genome. Fu also investigated mtDNA deletions and their impact on cellular metabolism. Now, Fu will leverage genomics and single-cell technologies to elucidate the dynamic regulation of mtDNA during her postdoctoral research.
Indiana University
Appointed in 1980
Stanford University
Appointed in 1977
Columbia University
Appointed in 1987
National Cancer Institute / NIH
Appointed in 2021
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National Cancer Institute / NIH
Appointed in 2021
Enhancers are distal cis-regulatory elements that control precise execution of transcriptional programs during development and in response to external stimuli. How enhancers find and activate their target genes, and what molecular activities are required for enhancer function remains a central outstanding question in the field. Recent advances in nascent RNA-sequencing uncovered widespread transcription from enhancers, which has become widely recognized as a robust signature of enhancer activity. However, mechanistic understanding of enhancer transcription, its regulation and, most importantly, functional role in gene activation is currently missing.
In my work, I aim to address these fundamental questions by using single-molecule and live-cell imaging approaches to characterize the intrinsic dynamics of enhancer transcription in single cells. To generalize my conclusions from individual enhancers to a genome scale, my ultimate goal is to develop high-throughput single-molecule approaches for systematic characterization of enhancer transcription. Using these new tools, I will investigate how transcription at enhancers and their target gene promoters is coordinated at the single-cell level to discover if these processes are functionally linked. Together, this work will be an essential step towards a deeper mechanistic understanding of enhancer function in gene activation and how enhancer perturbations can lead to severe developmental disorders and cancer.
MRC Center, University Medical School, England
Appointed in 1978
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MRC Center, University Medical School, England
Appointed in 1978
University of Southern California, Los Angeles
Appointed in 1996
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University of Southern California, Los Angeles
Appointed in 1996
Lawrence Berkeley National Laboratory /
University of California, Berkeley
Appointed in 2003
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Lawrence Berkeley National Laboratory / University of California, Berkeley
Appointed in 2003
University of California, San Francisco
Appointed in 1998
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University of California, San Francisco
Appointed in 1998
Princeton University
Appointed in 1992
University of Cambridge, England
Appointed in 1991
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University of Cambridge, England
Appointed in 1991
University of Texas Southwestern Medical Center
Appointed in 2020
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University of Texas Southwestern Medical Center
Appointed in 2020
California Institute of Technology
Appointed in 1976
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California Institute of Technology
Appointed in 1976
Scripps Research Institute
Appointed in 2005
University of California, Berkeley
Appointed in 2006
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University of California, Berkeley
Appointed in 2006
Public Health Research Institute of the City of New York
Appointed in 1955
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Public Health Research Institute of the City of New York
Appointed in 1955
Whitehead Institute for Biomedical Research
Appointed in 1990
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Whitehead Institute for Biomedical Research
Appointed in 1990
Fred Hutchinson Cancer Center
Appointed in 2015
With a high prevalence of sugar in our society, especially in the form of sugar-sweetened drinks, it is important to understand the relationships between sugar metabolism and critical events in cancer progression. Recent research shows that sugar metabolism can promote oncogenesis in cell culture models of breast epithelial cells. This research was done with the sugar glucose, but breast cancer cells also have the unique ability to uptake fructose, while normal breast epithelial cells do not. Fructose and glucose are both simple sugars that are present in equimolar amounts in most of the food we eat. Although fructose is naturally found in fruits and vegetables, it is also added as high fructose corn syrup to many drinks and processed foods. More research needs to be done on how cancer cells respond to conditions with fructose and glucose. I am using breast cancer cell culture models to investigate the effects fructose and glucose have on cancer cell growth. By focusing on differences in regulation of gene expression with exposure to different sugars, we aim to discover the mechanisms fructose uses to fuel cancer cell growth. We hope this work will lead to better informed dietary recommendations for breast cancer patients and those with an increased risk for breast cancer.
Rockefeller University
Appointed in 1991
University of California, Berkeley
Appointed in 2012