Massachusetts General Hospital
Appointed in 2009
Histone lysine tri-demethylases regulate cell cycle progression
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.
Harvard University
Appointed in 1999
Explore Fas signaling with a synthetic trimerizer
New York University
Appointed in 2021
A novel single-cell phospho-protein and chromatin accessibility assay
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.
Stanford University
Appointed in 1985
Measurement of myosin movement along actin filaments
University of Colorado, Boulder
Appointed in 1976
Read more
University of Colorado, Boulder
Appointed in 1976
Characterization of E coli translational mutants
University of California, Santa Barbara
Appointed in 1980
Read more
University of California, Santa Barbara
Appointed in 1980
Protein binding to yeast centromeric DNA
Imperial Cancer Research Fund Laboratories, England
Appointed in 1972
Read more
Imperial Cancer Research Fund Laboratories, England
Appointed in 1972
Virons of RNA tumor viruses
University of California, San Francisco
Appointed in 2007
Read more
University of California, San Francisco
Appointed in 2007
ParM plays a central role in bacterial plasmid segregation
University of California, San Francisco
Appointed in 2014
Read more
University of California, San Francisco
Appointed in 2014
Germline rejuvenation in C. elegans
The survival of a species requires that age must be reset with each generation. How germ cells, the reproductive cells of animals, accomplish this feat remains a fundamental, unsolved question in biology.
Utilizing the genetically-tractable nematode¬†Caenorhabditis elegans,¬†my research aims to identify mechanisms that cleanse the germ lineage of cellular damage and thereby allow for trans-generational rejuvenation. As a JCC fellow in Dr. Cynthia Kenyon’s lab, I have uncovered a regulatory switch that links damage elimination to fertilization and establishes a clean slate for the next generation prior to embryogenesis. Currently, I am exploring the molecular underpinnings of this switch in more detail.
Because molecules that ensure the immortality of the germ lineage might be capable of rejuvenating diverse cell types, I am also testing whether these natural age-reversal strategies can be co-opted in somatic tissues. If so, mechanisms important for germline immortality might provide a promising entry point for reversing whole-organism aging.
University of California, San Francisco
Appointed in 2014
Read more
University of California, San Francisco
Appointed in 2014
Regulation of gene expression by ribosomal proteins
University of California, Berkeley
Appointed in 2015
Read more
University of California, Berkeley
Appointed in 2015
Genetic regulation of multicellularity in a close relative to metazoans
The evolution of regulatory mechanisms to coordinate multicellular development was critical to the origin of animals. Fundamental mechanisms that led to animal multicellularity may also be conserved in the closest living relative of animals, the choanoflagellates, since one species, Salpingoeca rosetta, can transition to a multicellular form called a rosette in a process that is reminiscent of early embryogenesis in animals. To uncover how this multicellular transition is controlled in S. rosetta, we are establishing transgenic and genomic methods that will enable investigating how genes coordinate rosette development. These advances will provide essential tools for exploring the molecular biology of these ecologically and evolutionarily important organisms and potentially illuminate the earliest stages of animal evolution and development.
University of Washington, Seattle
Appointed in 1974
Read more
University of Washington, Seattle
Appointed in 1974
Molecular analysis of yeast DNA
University of Wisconsin, Madison
Appointed in 1994
Read more
University of Wisconsin, Madison
Appointed in 1994
Characterization of signal transductions
Massachusetts Institute of Technology
Appointed in 1975
Read more
Massachusetts Institute of Technology
Appointed in 1975
kPost-transcriptional controls of animal viruses
Stanford University School of Medicine
Appointed in 2014
Read more
Stanford University School of Medicine
Appointed in 2014
Consequences of P52 activation during development
The p53 protein is a transcription factor that becomes activated in response to various cellular stress cues. Once activated, p53 induces target genes involved in apoptosis, cell cycle arrest, senescence and differentiation. Maintaining the correct levels of p53 is critical, since loss of p53 promotes cancer, while increased p53 activity promotes developmental defects and premature aging. To further define the consequences of increased p53 activity, the Attardi lab created a novel mouse model in which p53 is activated during embryogenesis. Intriguingly, this led to a variety of craniofacial and cardiovascular defects. This unique constellation of phenotypes is reminiscent of human CHARGE syndrome, which is caused by mutations in CHD7. I am now using our p53 mouse models to study the cellular and molecular mechanisms by which p53 promotes features of CHARGE syndrome. These studies will further our understanding of p53 as a mediator of developmental disease in addition to its role as a tumor suppressor.
Fred Hutchinson Cancer Center
Appointed in 1989
Read more
Fred Hutchinson Cancer Center
Appointed in 1989
Early determinants of neuronal fate in the nematode
University of Pennsylvania
Appointed in 2019
Molecular regulation of behavioral and reproductive plasticity in ants
Australian National University, Australia
Appointed in 1976
Read more
Australian National University, Australia
Appointed in 1976
Rockefeller University
Appointed in 1975
Molecular mechanisms of cel-cell interactions
Stanford University
Appointed in 2001
Calmodulin binding and trapping by CaM kinase II
Massachusetts General Hospital
Appointed in 2012
Read more
Massachusetts General Hospital
Appointed in 2012
Driving differentiation of retinal glia
Stanford University
Appointed in 1981
ATP-dependent clathrin disassembly
California Institute of Technology
Appointed in 2024
Read more
California Institute of Technology
Appointed in 2024
Defining the role of protein homeostasis in spermatogenesis
Traditionally, structural biology efforts have been limited to studying purified samples in isolation. While we have learned a great deal via these efforts, such approaches unfortunately strip away much of the biological context from the sample of interest.
Dr. Julian Braxton will overcome these limitations by using cryo-electron tomography (cryo-ET) to examine proteostasis, or the process by which cells maintain the proper balance, folding, and function of proteins, within sperm cells in Dr. Zhen Chen’s lab at the California Institute of Technology. Proteostasis plays important yet understudied roles in cellular development processes, as the proteome must be reprogrammed to enable new functions. Braxton will apply cellular cryo-ET to analyze such developmental processes in mammalian sperm, where highly specialized functional compartments are assembled. This research will provide foundational understanding into the posttranslational regulation of sperm maturation and expand the frontier of cryo-ET development and analysis.
Braxton’s expertise in proteostasis stems from his graduate studies in Dr. Daniel Southworth’s lab at the University of California, San Francisco. There, Braxton used the related structural technique cryo-EM to reveal the intricate details of how the autophagy-related adapter UBXD1 regulates the hexameric AAA+ chaperone p97. His findings revealed that UBXD1 separates two adjacent p97 protomers to open the p97 ring, allowing for a new mode of substrate entry and/or exit into the p97 central pore. In a related project, Braxton revealed a novel asymmetric state of the mitochondrial chaperone Hsp60 that enables client refolding. In his postdoctoral work, Braxton will expand his structural biology toolkit to include cryo-ET and use this technique to provide unprecedented insight into the role of nuclear proteasomes in spermatogenesis.
University of Colorado, Boulder
Appointed in 2003
Read more
University of Colorado, Boulder
Appointed in 2003
Role of mitochondria during apoptosis in C elegans
Stanford University
Appointed in 1964
Nucleic acid metabolism and protein synthesis
Stanford University
Appointed in 2020
Mechanisms of R-loop mediated innate immune response in non-dividing cells
Washington University in St. Louis
Appointed in 1974
Read more
Washington University in St. Louis
Appointed in 1974
Mitogenic effects of certain lectins
University of Washington, Seattle
Appointed in 1982
Read more
University of Washington, Seattle
Appointed in 1982
Dosage compensation in Drosophila LSPI-alpha gnes
St. Jude Children's Hospital
Appointed in 2012
Read more
St. Jude Children's Hospital
Appointed in 2012
Anaphase-promoting complex ubiquitination mechanisms
Massachusetts Institute of Technology
Appointed in 2013
Read more
Massachusetts Institute of Technology
Appointed in 2013
Elucidating the role of the E. coli Lon protease N-domain in substrate recognition and discrimination
My primary research interest is studying the molecular basis of the diverse protein-protein interactions that underlie bacterial cell signaling. I am currently focusing on determining the various types of substrate interactions mediated by the E. coli Lon protease to understand how this critical regulator degrades certain proteins during cellular stress. Lon is one of the major proteases that mediates protein quality control via degradation of over half of the unfolded or misfolded proteins in the cell. Additionally, Lon degrades stably-folded regulatory proteins involved in response to several stresses such as DNA damage, heat shock, and oxidation. Using a combination of biophysical and biochemical assays, including electron microscopy, X- ray crystallography, analytical ultracentrifugation, and enzyme kinetics, my current goal is to identify the molecular interactions critical for Lon self-assembly and substrate recognition. With this detailed information, we can begin to understand in greater detail how Lon discriminates among various substrates to regulate critical cellular stress responses and survival.
University of Oregon
Appointed in 1991
Receptor-mediated signal transduction in yeast
Brigham and Women's Hospital
Appointed in 2017
Read more
Brigham and Women's Hospital
Appointed in 2017
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._x000D_
_x000D_
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._x000D_
_x000D_
_x000D_
_x000D_
Harvard University
Appointed in 1991
d. melanogaster tra-2 funtion in the male germ line
Yale University
Appointed in 1973
Quantitation of chromosomal content in cell fusion hybrids
Harvard University Medical School
Appointed in 2021
Read more
Harvard University Medical School
Appointed in 2021
The role of p53 dynamics in immune cell regulation
In response to DNA damage, the tumor suppressor protein p53 induces expression of stress-responsive genes to inhibit proliferation of cells with damaged DNA. Changes in p53 protein levels over time (p53 dynamics) impact cellular outcomes: p53 oscillations facilitate repair of DNA-damaged cells, whereas sustained levels of p53 promote senescence and cell death. While it is now established that p53 dynamics contribute to these competing cell-autonomous processes, how p53 dynamics regulate genes involved in non-cell-autonomous events, such as those involved in immune signaling, is not known. I propose to develop new tools and approaches to study the role of p53 in regulating immune gene expression in cancer cells and in mediating the killing of cancer cells by immune cells. This research will provide fundamental insights into the mechanisms that govern of cancer cell-immune cell interactions and pave the way for developing effective combination therapies to treat cancer
Cold Spring Harbor Laboratory
Appointed in 1969
Temperate phage Mu-1 in chromosome of E. coli
Cold Spring Harbor Laboratory
Appointed in 1971
Temperate phage Mu-1 in chromosome replication
University of California, Los Angeles
Appointed in 2013
Read more
University of California, Los Angeles
Appointed in 2013
A novel bulk segregant method to identify natural genetic variants underlying Caenorhabditis elegans resistance to chemotherapy drugs
Massachusetts Institute of Technology
Appointed in 2016
Read more
Massachusetts Institute of Technology
Appointed in 2016
Investigating mechanisms of immune evasion in autochthonous lung tumors
University of Washington, Seattle
Appointed in 1983
Read more
University of Washington, Seattle
Appointed in 1983
Genetic analysis of centromere replication
National Institutes of Health
Appointed in 1956
University of Oxford, England
Appointed in 1961
Read more
University of Oxford, England
Appointed in 1961
Tumor enzymology
Yale University
Appointed in 1997
Cell cycle control by regulated protein degradation
University of California, Los Angeles
Appointed in 1995
Read more
University of California, Los Angeles
Appointed in 1995
NMR Studies of the hairpin ribozyme
Harvard University
Appointed in 2011
Bacterial biofilm regulation by D-amino acids
University of California, Berkeley /
Stanford University
Appointed in 1979
Read more
University of California, Berkeley / Stanford University
Appointed in 1979
Electrical properties of niological membranes
University of Oregon, Eugene
Appointed in 2019
Defining mechanisms of heat-sensitive synaptonemal complex in spermatocytes
Sexually reproducing organisms faithfully transmit their genome to the next generation by forming haploid gametes, such as eggs and sperm. In contrast to oogenesis and other developmental processes, spermatogenesis is sensitive to small temperature changes, requiring a narrow isotherm of 2-7ºC below basal body temperature. Although failure to precisely thermoregulate spermatogenesis or exposure to elevated temperatures are strongly linked to both male infertility and an increased risk of testicular cancer, the mechanisms behind temperature-induced damage on male reproductive health remain unknown. Recent studies indicate that the composition and/or function of chromosome structures differ during oogenesis and spermatogenesis, which may contribute to the temperature-sensitivity of spermatogenesis. In Caenorhabditis elegans, we have found using structured illumination microscopy that the synaptonemal complex (SC), a meiosis specific structure central to the proper execution of key meiotic processes, is destabilized specifically in spermatocytes and not oocytes following heat-stress. My ongoing studies seek to understand the differences in SC organization and composition that render it temperature sensitive only in spermatogenesis. Overall, these studies will illuminate how temperature specifically affects genome integrity in developing sperm and identify the mechanisms that underlie temperature-associated infertility and cancer risk of the male germline.
University of California, San Francisco /
Yale University
Appointed in 2008
Read more
University of California, San Francisco / Yale University
Appointed in 2008
Actin cytoskeleton reorganization during tubulogenesis
Current Research: The role of actin cytoskeleton remodeling during epithelial morphogenesis.
Prior to coming to the United States in 2003, I received bachelor’s degree in science from Fudan University in Shanghai, China. My undergraduate thesis topic was characterization of bacteriophage T3 DNA ligase.¬î My graduate study was done under Dr. James E. Bear in the Department of Cell and Developmental Biology at the University of North Carolina, Chapel Hill. My dissertation title was “Coronin 1B coordinates actin dynamics in lamellipodia.¬î ¬†Currently, I am working with Dr. Keith Mostov in the Department of Anatomy at UCSF. ¬†I really enjoy the life of doing research, and am looking forward to continuing my scientific journey. In my free time, I like to hike and ski.”
Baylor College of Medicine
Appointed in 1997
Genome-wide monitoring of genetic changes in cancer development
Stanford University
Appointed in 1977
Chromosomal organization
Chemisches Institut der Universitat, Switzerland
Appointed in 1951
Read more
Chemisches Institut der Universitat, Switzerland
Appointed in 1951
Carcinogenesis