Pharmacology

Basil P Hubbard

Dr Basil P Hubbard

Assistant Professor
Canada Research Chair in Molecular Therapeutics

Education:
BSc (Hons), Biochemistry, University of Ottawa, 2005
PhD, Biological and Biomedical Sciences, Harvard University, 2011

Teaching: PMCOL300, PMCOL401/402, PMCOL498

Research: Next-generation therapies for diseases of aging

Research Interests / Laboratory Techniques

As we age, the biomolecules within each of our cells, including DNA, proteins, and lipids, undergo damaging chemical reactions. These alterations can culminate in the development of numerous age-related diseases such as cancer, Alzheimer’s, and diabetes. Unfortunately, due to the complex nature of these diseases, many them can’t be treated in a safe and effective manner using traditional small-molecule pharmaceuticals. The Hubbard lab develops and explores the use of unconventional next-generation therapies for the treatment of cancer and other age-related pathologies.

Our lab is heavily engaged in developing new technologies including gene editing systems that can directly reverse disease-causing mutations (e.g. CRISPR/Cas9), biologics and xenobiologics capable of regulating targets considered non-druggable (e.g. synthetic peptides and nucleic acids), and support systems for cell-based therapies (e.g. cryoprotective agents). Because many macromolecular therapeutics are too large to penetrate into cells, we are also working on new paradigms for their intracellular delivery. Some of these include the use of specialized cell penetrating biomolecules and viruses.

While we predominately focus on applying these tools to better understand and treat cancer and age-related disorders, we envision that our fundamental technological developments will have broad medical significance, with implications for the treatment of hereditary and infectious diseases also.

Selected Recent Publications

Cromwell CR, Sung K, Park J, Krysler AR, Jovel J, Kim SK, Hubbard BP. (2018) Incorporation of bridged nucleic acids into CRISPR RNAs improves Cas9 endonuclease specificity. Nature Communications 9(1):1448. PMID: 29654299.

Li J, Bonkowski MS, Moniot S, Zhang D, Hubbard BP, Ling AJ, Rajman LA, Qin B, Lou Z, Gorbunova V, Aravind L, Steegborn C, Sinclair DA. (2016) A conserved NAD+ binding pocket that regulates protein-protein interactions during aging. Science 355(6331):1312-1317. PMID: 28336669.

Van Meter M, Simon M, Tombline G, May A, Morello TD, Hubbard BP, Bredbenner K, Park R, Sinclair DA, Bohr VA, Gorbunova V and Seluanov A. (2016) JNK Phosphorylates SIRT6 to Stimulate DNA Double-Strand Break Repair in Response to Oxidative Stress by Recruiting PARP1 to DNA Breaks. Cell Reports 16(10):2641-50. PMID: 27508560.

Hubbard BP, Badran AH, Zuris JA, Guilinger JP, Davis KM, Chen L, Tsai SQ, Sander JD, Joung JK, Liu DR. (2015) Continuous directed evolution of DNA-binding proteins to improve TALEN specificity. Nature Methods 12(10):939-42. PMID: 26258293.

Hubbard BP, Gomes AP, Dai H, Li J, Case AW, Considine T, Riera TV, Lee JE, E SY, Lamming DW, Pentelute BL, Schuman ER, Stevens LA, Ling AJ, Armour SM, Michan S, Zhao H, Jiang Y, Sweitzer SM, Blum CA, Disch JS, Ng PY, Howitz KT, Rolo AP, Hamuro Y, Moss J, Perni RB, Ellis JL, Vlasuk GP, Sinclair DA. (2013) Evidence for a common mechanism of SIRT1 regulation by allosteric activators. Science 339(6124): 1216-1219. PMID: 23471411.