The Rosetta Institute of Biomedical Research is an independently funded medical research institute founded by Dr. Ryan Holzer, PhD. The institute is funded by internally generated revenue, and by private donations.
We conduct basic and translational research on cell death in multiple myeloma and lung cancer, with the ultimate goal of identifying novel driver mutations responsible for tumorigenesis and the emergence of chemoresistant clones. The primary model system is molecular evolution in response to various cytotoxic agents, including agents that disturb proteostasis, senolytics, and inhibitors of DNA replication. Under this umbrella, multiple overlapping themes are being investigated, including: 1) discovering novel mechanisms of bortezomib (Velcade) resistance in multiple myeloma and the identification of the bortezomib-resistant subclone, 2) transcriptomic analysis and miRNA profiling of clonal evolution in cancer, 3) the discovery of novel roles for IL-6 family cytokines in hematologic malignancies, 4) The identification of novel alternatively spliced transcripts that contribute to tumor progression and the RNA-binding proteins that regulate rare exon inclusion/exclusion, 5) the role and regulation of autophagy during proteotoxic stress, 6) adaptation to endoplasmic reticulum (ER) stress and mechanisms of ER stress-induced apoptosis, 7) the role of cell differentiation in drug resistance and the identification and characterization of the stem cell compartment, 8) the role of hypoxia in drug sensitivity and clonal evolution, 9) the role of senescence in drug resistance/drug sensitivity and the identification and characterization of the senescence-prone subclone, 10) the genetic basis for the co-emergence of the drug resistance and epithelial-mesenchymal transition (EMT) phenotypes, 11) The role of innate antiviral defense mechanisms in myeloma pathogenesis/progression and treatment response. A variety of techniques are being used at the Institute to address these questions, including tissue culture, bioinformatic analyses, CRISPR/Cas9 gene editing, and mass spectrometry. In addition, we are engaged in a drug discovery program to identify novel small molecules that combat cancer, neurodegenerative disorders, aging and other diseases related to senescence, splicing errors or disturbances in proteostasis.