University of Oregon
Appointed in 2003
The mechanism of cytokinesis
Rockefeller University
Appointed in 2012
Metabolic connections to pluripotent chromatin
King's College, London
Appointed in 1968
Viral and bacterial DNA
Massachusetts Institute of Technology
Appointed in 1978
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Massachusetts Institute of Technology
Appointed in 1978
Regulation of sucrose utilization in yeast
Swiss Institute of Experimental Cancer Research, Switzerland
Appointed in 1975
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Swiss Institute of Experimental Cancer Research, Switzerland
Appointed in 1975
Affinity chromatography
University of California, Berkeley
Appointed in 2006
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University of California, Berkeley
Appointed in 2006
Controlling metabolic pathways with RNA aptamers
University of California, Santa Barbara
Appointed in 1983
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University of California, Santa Barbara
Appointed in 1983
Yeast centromere structure and function
Beatson Institute for Cancer Research, Scotland
Appointed in 1970
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Beatson Institute for Cancer Research, Scotland
Appointed in 1970
DNA template activity
University of California, San Francisco
Appointed in 2003
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University of California, San Francisco
Appointed in 2003
Harvard University Medical School
Appointed in 2020
Zinc finger TFs in activity-dependent human neuronal gene regulation
California Institute of Technology
Appointed in 1958
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California Institute of Technology
Appointed in 1958
Chemical structure of RNA from tobacco mosaic virus
Harvard University Medical School
Appointed in 2005
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Harvard University Medical School
Appointed in 2005
Molecular mechanisms to degrade abnoraml proteins
Stanford University School of Medicine
Appointed in 2006
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Stanford University School of Medicine
Appointed in 2006
Investigation of asymmetric RNA localization
University of California, San Francisco
Appointed in 2017
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University of California, San Francisco
Appointed in 2017
Novel effectors of oncogenic KRAS that regulate cell signaling
Stanford University School of Medicine
Appointed in 2013
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Stanford University School of Medicine
Appointed in 2013
Effects of irradiation injury on systemic-neurogenic communication as targets for limiting cognitive dysfunction
During my Ph.D. studies at Washington University, I worked with David Holtzman to show that ApoE e4 may increase Alzheimer’s disease risk by impairing Ab clearance from the brain, thus shifting the onset of its accumulation. My interest in neurodegeneration and aging motivated me to understand factors that regulate aging and brain health in unconventional ways. My project as a Jane Coffin Childs fellow in Tony Wyss-Coray’s laboratory has been to elucidate a novel systemic-neurogenic communication mechanism that appears to be disrupted in the context of brain irradiation therapy. Specifically, I am investigating the role of immune signaling molecules in mediating the neurogenic and cognitive dysfunction observed in the post-irradiation syndrome in pediatric brain cancer patients. Additionally, I am actively pursuing whether related blood-borne signaling molecules in young plasma may be sufficient to ameliorate age-related decreases in cognition and synaptic plasticity. To examine these complex mechanisms, I am leveraging various physiological methods, including plasma transfer and parabiosis.
Yale University /
University of California, Berkeley
Appointed in 1974
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Yale University / University of California, Berkeley
Appointed in 1974
Release of secretory proteins
University of California, San Francisco
Appointed in 2021
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University of California, San Francisco
Appointed in 2021
Biophysical dissection of implantation defects resulting from maternal aging
Infertility represents a significant societal burden, as nearly 60% of human pregnancies fail before the embryo implants into the uterus. These miscarriages become more prevalent as women age above 35 years. But implantation remains a black box within development because it occurs within the mother’s body, so progress revealing its physical mechanisms is lagging. Early in preimplantation sages, primitive placental lineages must be specified for faithful implantation. Driving these lineage commitments are subcellular mechanical forces that transduce expression of downstream fate determinants for specification and ultimate invasion of placental tissues. However, in mammalian embryos of aged mothers, embryos display poor developmental health with decreased placental structures owing to impaired implantation. We hypothesize that these pathologies may stem from either early defects in tissue specification or later mechanical uterine invasion, both of which could give rise to age-related spontaneous abortions. This proposal therefore seeks to understand how the early cell biological and biophysical mechanisms are altered in the embryo with advanced maternal age, and how these mechanisms can be tuned to rejuvenate “aged” embryos to rescue developmental potential. Working in embryos of aged mice, we will combine approaches from cell and developmental biology, biophysics, and synthetic biology to ask: (1) Does maternal aging decouple the embryo’s upstream mechanics from downstream signal transduction during placental fate acquisition? (2) Is the logic of signal transduction for placental fate determinants altered via maternal aging? and (3) Do these age-related mechanisms together promote defective mechanical invasion during uterine implantation? Bridging these disparate scientific spheres will be critical in understanding infertility and improving female reproductive longevity.
University of California, Los Angeles
Appointed in 2003
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University of California, Los Angeles
Appointed in 2003
Genetic screen for regulators of neural connectivity
Harvard University
Appointed in 1975
Massachusetts Institute of Technology
Appointed in 1982
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Massachusetts Institute of Technology
Appointed in 1982
Developmental neurobiology
Duke University
Appointed in 1992
Chlamydomonas genes in chloroplast DNA repair
University of California, Berkeley
Appointed in 2001
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University of California, Berkeley
Appointed in 2001
Harvard University
Appointed in 2006
Multicellularity in Bacillus subtilis
Salk Institute for Biological Studies
Appointed in 1994
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Salk Institute for Biological Studies
Appointed in 1994
Identification of putative retinoic acid cistrans isomerase
Universite de Paris, France
Appointed in 1971
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Universite de Paris, France
Appointed in 1971
Regulation of cellular differentiation in B. subtilis
Massachusetts Institute of Technology
Appointed in 1982
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Massachusetts Institute of Technology
Appointed in 1982
Genetic control of cell lineage in c. elegans
Insitut for Biochemie, Max-Planck-Institut
Appointed in 1959
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Insitut for Biochemie, Max-Planck-Institut
Appointed in 1959
Syntesis of steroids
University of Washington, Seattle
Appointed in 1974
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University of Washington, Seattle
Appointed in 1974
Whitehead Institute for Biomedical Research
Appointed in 1996
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Whitehead Institute for Biomedical Research
Appointed in 1996
Structural basis of membrane fusion in HIV infection
Harvard University
Appointed in 2021
The evolution of complex chemosensation
How animal brains evolved the capacity for sophisticated computation is not well understood. One major facet of this problem is the evolution of chemosensation. Chemosensation is the primary sense of most animals, and involves complex neural computations. We do not know how this sense evolved, or how most animals – which are aquatic invertebrates – perform chemosensation. I am studying chemosensation in an acoel worm, an aquatic invertebrate that by virtue of its phylogenetic position as the likely outgroup to all other animals with central nervous systems, retains some primitive features of early central nervous systems. Acoels nonetheless perform sophisticated behavior that requires complex chemosensory processing, but how their brains and chemosensors work is unknown. Using a combination of automated behavioral tracking, transgenics, and neural activity imaging, I aim to understand the logic of chemosensory processing in a tractable acoel worm. Through comparisons with known chemosensory mechanisms of other animals, this will shed light on how complex chemosensory systems evolved. This project will also establish experimental approaches for the future study of neural computations and behavior in acoel worms and other aquatic invertebrates.
Yale University
Appointed in 2011
Sensing gut microbiota through G-protein coupled receptors
Massachusetts Institute of Technology
Appointed in 2002
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Massachusetts Institute of Technology
Appointed in 2002
Fluorescent probes for the roles of NO in cancer
University of California, Berkeley
Appointed in 2005
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University of California, Berkeley
Appointed in 2005
Engineering E coli for production of anticancer drug
Harvard University Medical School
Appointed in 2012
Single particle flavivirus membrane fusion
Harvard University
Appointed in 1982
Structure and biology of genes in the murin S region
Carnegie Institute for Science
Appointed in 1991
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Carnegie Institute for Science
Appointed in 1991
Mechanisms of transcriptional activation by C/EPB
Whitehead Institute for Biomedical Research
Appointed in 1987
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Whitehead Institute for Biomedical Research
Appointed in 1987
Analysis of the adipocyte glucose transporter
Centre Nationale de la Recherche Scientifique, France
Appointed in 1966
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Centre Nationale de la Recherche Scientifique, France
Appointed in 1966
Biosynthetic pathway of DPA in B. subtilis
University of California, San Diego
Appointed in 2003
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University of California, San Diego
Appointed in 2003
Dissecting kinetohore function in C Elegans
Harvard University
Appointed in 2005
Stanford University
Appointed in 2007
Mechanism of airway tube size control during lung development
Scripps Research Institute
Appointed in 1989
Catalytic antibodies
Harvard University Medical School
Appointed in 2012
RNA circuits for cancer theranostics
Harvard University Medical School
Appointed in 2014
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Harvard University Medical School
Appointed in 2014
Molecular dynamics of oncogene-induced senescence
Dana-Farber Cancer Institute
Appointed in 2015
The role of Kcnk3 and membrane potential in adipose tissue thermogenesis
My current research focuses on the molecular mechanisms underlying adipose tissue development and metabolism. In particular, I use genetic and biochemical approaches to identify the molecular differences between the energy-storing white fat and energy-dissipating brown/beige fat in the hope of using those differences to help design therapeutic strategies for the prevention and treatment of obesity._x000D_
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Brown and beige fat dissipates energy as heat in a process known as non-shivering thermogenesis. The transcriptional regulator Prdm16 was previously identified to facilitate thermogenesis; however, its relevant target genes remain incompletely known. Through ChIP-Seq and RNA-Seq, we have identified a number of potential Prdm16 targets. Among those, I focus on delineating the functions of a rectifying potassium channel Kcnk3 in thermogenesis. Kcnk3 is known to set the plasma membrane potential by generating potassium currents in neurons. I hypothesize that Kcnk3 sets the appropriate membrane potential in thermogenic adipocytes, which may be important for thermogenesis. I will test this hypothesis using fat-specific Kcnk3 knockout mice.
University of California, San Francisco
Appointed in 2015
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University of California, San Francisco
Appointed in 2015
Understanding liver bile duct formation to grow biliary tubes in vitro
Stanford University
Appointed in 2016
Dissecting the protein folding mechanism by the TRiC chaperonin
Proteostasis is a central mechanism to regulate the health of the cellular proteome. Proteostasis dysfunction has been directly implicated in age-related diseases, including cancer. A central but very poorly understood component of proteostasis network is the eukaryotic chaperonin, TRiC/CCT. TRiC is an essential chaperone that assists folding and assembly of many proteins fundamentally important to cancer, including the tumor suppressors p53, VHL, telomerase as well as other cell cycle regulators. It is, therefore, not surprising that mis-regulation of TRiC is also linked to numerous pathological conditions. Indeed, several TRiC subunits are highly up-regulated in cancer, and their up-regulation is linked to poor prognosis. The paucity of structural and mechanistic knowledge on this complex has hindered the development of therapeutic strategies targeting TRiC. Therefore, my research in the Frydman lab focuses on closing this gap by defining the molecular basis of human TRiC to fold the key disease-linked proteins. I am interested in combining biochemical and structural methods to elucidate the underlying principles by which TRiC recognizes and folds proteins. I anticipate the result of this work will provide mechanistic insights relevant to human diseases.
University of California, San Francisco
Appointed in 2016
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University of California, San Francisco
Appointed in 2016
Systemic analysis of the relationship between incRNAs and translation
Long non-coding RNAs (lncRNAs) have recently emerged as key functional molecules in gene regulation, with increasing evidence pointing to a role for lncRNAs in human diseases such as cancer. While the importance of a subset of nuclear lncRNAs in epigenetic and transcriptional gene regulation is well established, lncRNAs are also found in the cytoplasm and may function in different cytoplasmic processes including translational control. In particular, lncRNAs may regulate the translation of other transcripts; or, they may be associated with ribosomes and translated to produce short regulatory “micropeptides”. However, studying the roles for lncRNAs in translation has been hindered by the lack of high-throughput methods to systematically identify lncRNA candidates and probe how lncRNAs act globally to impact translation. Here, I propose a research program that uses a repertoire of genome-wide techniques, combining CRISPR interference and ribosome profiling, to provide fundamental insights into the novel role of lncRNAs in translational control.
Stanford University
Appointed in 2020
Dissecting the mechanisms of vertebrate reproductive aging in killfish
Reproductive aging is a global challenge. Older men and women face fertility loss and a higher chance of having children with genetic disorders. Currently, we lack a detailed molecular understanding of what causes reproductive aging in vertebrates. I am developing an emerging short-lived model system, the African killifish, to study vertebrate reproductive aging. The lifespan of this organism is 4 times shorter than mice and 7 times shorter than zebrafish. I will combine my graduate training (gamete biology) with the expertise of the Brunet Lab (killifish and aging) to probe the molecular basis of age-dependent fertility decline in the killifish and identify potential targets for therapeutic intervention. These studies will shed light on methods to protect or rejuvenate the germline from aging, which can have a profound impact on human fertility.
Michigan State University
Appointed in 1965
Action of gibbrelin on germination enzymes
Rockefeller University
Appointed in 1972
Viral carcinogenesis