Carl D. Novina
Though it has historically focused on fundamental biological questions, the Novina lab places a significant emphasis on identifying unmet medical needs and developing technologies to address those needs. We work very closely with Dana-Farber and other HMS-affiliated clinicians who wish to translate our technologies into therapies for their patients. Our clinical collaborators work with us to generate investigational new drug (IND)-enabling data so that they can submit physician-initiated clinical trials using Novina lab technologies. We are currently developing technologies for multiple myeloma, ovarian cancer, and brain cancer immunotherapies including a CRISPR-Cas9 epigenetic reprogramming platform and novel autologous cell therapies. A major focus of the lab is the fundamental biology of non-coding RNAs (ncRNAs) and their dysregulation in disease. Because RNAs are so versatile, the Novina Lab also develops RNA-based tools for biomedical research and therapeutic applications.
While less than 2% of our genome make proteins, more than 75% of our genome make RNAs that do not encode proteins. These RNAs can be master regulators of biological processes, can form three dimensional structures, and can catalyze enzymatic reactions (like proteins). Despite the critical role that ncRNAs play in human disease and the recent success of RNA-based therapies, it is still unclear how many ncRNAs function and how they may be targeted for therapy.
We have taken a protein-based approach to understanding RNA biology. My lab has a long history studying microRNAs, but more recently has focused on long non-coding RNA (lncRNAs). We discovered a lncRNA called SLNCR that is abundantly expressed in human melanomas. SLNCR complexes with one set of proteins to mediate invasion (Cell Reports, 2016 and 2020) and an alternate set of proteins to mediate proliferation (Cell Reports, 2019). In each of these cases, identifying the interacting proteins holds the key to discovering the underlying biology of the non-coding RNA function.
There are several technological challenges to discovering which proteins bind to which RNAs. For example, most traditional biochemical approaches (e.g. RNA precipitation followed by mass spectrometry) are unable to capture weak or transient interactions but instead enrich the most abundant RNAs and proteins with the highest affinity. To address these limitations, the Novina lab developed a sensitive and specific assay called RATA (RNA-associated Transcription Factor Array) that can identify transcription factors interacting with any RNA of interest (Cell Reports, 2016; J. Biol. Methods, 2017). More recently, we have also developed a high-throughput platform technology that allows for systematic testing of every protein in the human proteome against any RNA of interest. This latter technology can be used to define the RNA sequence and structural determinants of protein interaction and can even be used to discover small molecules that disrupt disease-causing RNA-protein interactions.
I am committed to personalizing my training based on the career ambitions of each student, whether they want a scientific career in academia or industry, or an alternative career path (e.g. patent law or business development). For more on my perspectives on developing, translating, and commercializing technologies to address unmet medical needs, please visit the Novina Lab website or read my chapter in a recently published biotechnology textbook, “Translational Research In Academia – Moving Towards The D Side Of R&D” in Biotechnology: From Idea to Market”, which is available at Countway Library.
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