BBS Faculty Member - Carl Novina

Carl Novina

Department of Medicine

Dana Farber Cancer Institute
Smith Building, Room 552
450 Brookline Avenue
Boston, MA 02215
Tel: 617-582-7961
Fax: 617-582-7962
Email: carl_novina@dfci.harvard.edu
Visit my lab page here.



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.
http://id.lib.harvard.edu/alma/99153820052603941/catalog



Last Update: 7/8/2020



Publications

For a complete listing of publications click here.

 


 

Targeting the oncogenic long non-coding RNA SLNCR1 by blocking its sequence-specific binding to the androgen receptor. Schmidt K, Weidmann CA, Hilimire TA, Yee E, Hatfield BM, Schneekloth JS, Weeks KM, Novina CD. Cell Reports 2020; 30(2):541.

The lncRNA SLNCR1 recruits the androgen receptor to EGR1-bound genes and melanoma and inhibits expression of tumor suppressor p21. Schmidt K, Carroll JS, Yee E, Thomas DD, Wert-Lamas L, Neier SC, Sheynkman G, Ritz J, Novina CD. Cell Reports 2019; 27:2493.

Hematopoietic architecture of Shwachman-Diamond Syndrome at single cell resolution. Joyce CE, Saadatpour A., Ruiz-Gutierez M, Bolukbasi OV, Jiang L, Thomas DD, Young S, Hofmann I, Sieff CA, Myers KC, Whangbo J, Libermann TA, Nusbaum C, Yuan GC, Shimamura A, Novina CD. J. Clin. Invest. 2019; 130:3821.

Targeted DNA methylation in human cells using engineered dCas9-methyltransferases. Xiong T, Meister GE, Workman RE, Kato NC, Spellberg MC, Turker F, Timp W, Ostermeir M, Novina CD. Scientific Rep. 2017; 7(1):6732.

RATA: A method for high-throughput identification of RNA bound transcription factors. Schmidt K, Buquicchio F, Carroll J, Distel RJ, Yoon CH, Novina CD. J. Biol. Methods. 2017; 4(1), e67.

The lncRNA SLNCR1 mediates melanoma invasion through a conserved SRA1-like region. Schmidt K, Joyce CE, Buquicchio F, Brown A, Ritz J, Distel RJ, Yoon CH, Novina CD. Cell Reports. 2016; 15(9):2025-37.

Textbook:
Biotechnology – From Idea to Market. Editors: Fred Mermelstein, Richard Prince and Carl Novina. Publisher: Davis Healthcare International (DHI) Books. September 2019. Available at Countway Library.



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