Person:
Thomas, Marshall

Profile Picture

Email Address

AA Acceptance Date

Birth Date

Research Projects

Organizational Units

Job Title

Last Name

Thomas

First Name

Marshall

Name

Thomas, Marshall
Author's Publications: search.filters.isAuthorOfPublication.de81a285-7b9d-4401-b91d-9ed6ef8e5e3c

Search Results

Now showing 1 - 2 of 2
  • Thumbnail Image
    Publication
    Novel Roles for Ribonucleic Acids in Programmed Cell Death
    (2014-10-22) Thomas, Marshall; Lieberman, Judy; Gregory, Richard; Danial, Nika; Moore, Melissa; Buratowski, Steven
    Apoptosis is a tightly coordinated program to shut down and dismantle a cell, characterized by mitochondrial outer membrane permeabilization (MOMP), caspase activation to cleave hundreds of proteins, DNA fragmentation, and blocked translation. Little is known about the fate of RNA as cells die, even though apoptosis has been intensively studied for decades. Here I show that mRNAs, but not noncoding RNAs (ncRNAs), are rapidly and globally degraded during apoptosis. The decay occurs in many cell types responding to diverse apoptotic stimuli. mRNA decay is triggered early in apoptosis, preceding membrane lipid scrambling, genomic DNA fragmentation and modifications to translation initiation factors that might cause translational arrest. mRNA decay depends on MOMP and is amplified by effector caspase activity. 3' truncated mRNA decay intermediates with nontemplated uridylate-rich tails are generated during apoptosis and degraded by the 3' to 5' exonuclease DIS3L2. Knockdown of DIS3L2 reduces apoptotic mRNA decay and partially rescues cell death. I propose that global mRNA decay is a new hallmark of apoptosis caused by the concerted action of several nucleases. I also report a new role for RNA and DNA in directing cytotoxic leukocyte proteases to their substrates. When cytotoxic lymphocytes recognize and attack infected or cancerous cells, they deliver the granzyme (Gzm) serine proteases into the target cell. The Gzms cleave diverse protein substrates to orchestrate cell death. RNA binding proteins are highly enriched in unbiased proteomic screens of Gzm protein substrates. I hypothesized that the Gzms are guided to nucleic acid binding protein targets via direct binding to RNA or DNA. Using fluorescence polarization, I show that the Gzms and related leukocyte proteases bind to RNA and DNA with low nanomolar affinity. Nucleic acid binding by the Gzms facilitates their cleavage of RNA and DNA binding proteins, and guides them into target cell nuclei and onto neutrophil extracellular traps. Nucleic acid binding provides an elegant mechanism to confer protease substrate specificity for cleavage of nucleic acid-binding proteins that play essential roles in cellular gene expression and cell proliferation.
  • Thumbnail Image
    Publication
    Protocol: Adaptive Implementation of Effective Programs Trial (ADEPT): cluster randomized SMART trial comparing a standard versus enhanced implementation strategy to improve outcomes of a mood disorders program
    (Springer Science + Business Media, 2014) Kilbourne, Amy M; Almirall, Daniel; Eisenberg, Daniel; Waxmonsky, Jeanette; Goodrich, David; Fortney, John C; Kirchner, JoAnn E; Solberg, Leif I; Main, Deborah; Bauer, Mark; Kyle, Julia; Murphy, Susan A; Nord, Kristina M; Thomas, Marshall
    Despite the availability of psychosocial evidence-based practices (EBPs), treatment and outcomes for persons with mental disorders remain suboptimal. Replicating Effective Programs (REP), an effective implementation strategy, still resulted in less than half of sites using an EBP. The primary aim of this cluster randomized trial is to determine, among sites not initially responding to REP, the effect of adaptive implementation strategies that begin with an External Facilitator (EF) or with an External Facilitator plus an Internal Facilitator (IF) on improved EBP use and patient outcomes in 12 months. This study employs a sequential multiple assignment randomized trial (SMART) design to build an adaptive implementation strategy. The EBP to be implemented is life goals (LG) for patients with mood disorders across 80 community-based outpatient clinics (N = 1,600 patients) from different U.S. regions. Sites not initially responding to REP (defined as <50% patients receiving ≥3 EBP sessions) will be randomized to receive additional support from an EF or both EF/IF. Additionally, sites randomized to EF and still not responsive will be randomized to continue with EF alone or to receive EF/IF. The EF provides technical expertise in adapting LG in routine practice, whereas the on-site IF has direct reporting relationships to site leadership to support LG use in routine practice. The primary outcome is mental health-related quality of life; secondary outcomes include receipt of LG sessions, mood symptoms, implementation costs, and organizational change. This study design will determine whether an off-site EF alone versus the addition of an on-site IF improves EBP uptake and patient outcomes among sites that do not respond initially to REP. It will also examine the value of delaying the provision of EF/IF for sites that continue to not respond despite EF.