Linda Penn

At A Glance

• Penn Lab Focus:  Exploiting Molecular Oncology to Trigger Tumour Cell Death
• Two major areas of research: i) identifying novel strategies to inhibit the MYC oncogene; ii) exploiting tumour metabolism and statin drugs as anti-cancer agents
• New technologies lead to new insights:  we help to develop new research tools to advance our understanding of basic molecular mechanisms of action
• Participates in multi-disciplinary collaborations: we interact with Researchers and Clinician Scientists, both close to home and globally, with complementary expertise to help us advance our research goals
• Emphasis on research with relevance: our mission is to provide new discoveries that will ultimately improve cancer patient care and outcome

Short Bio

Linda Penn is a Senior Scientist at the Princess Margaret Cancer Centre (PM), University Health Network (UHN), and Full Professor in the Department of Medical Biophysics (MBP) at the University of Toronto (UT). Dr. Penn earned her PhD in Microbiology and Medical Genetics at UT, for which she was awarded the L. W. MacPherson Award. Supported by a Medical Research Council Scholarship, Dr. Penn conducted her postdoctoral fellowship at the Imperial Cancer Research Institute (London, UK).

Dr. Penn started her own laboratory at the PM in 1996, was then the Division Head of Cancer Genomics and Proteomics (2005-2010) and served on the Research Executive Committee (2009-2012). With MBP she was on several committees and served as Head of Graduate Admissions and on the Executive Committee (2002-2004). Dr. Penn also held leadership roles with the UHN, as Platform Head of Genes, Proteins and People (2003-2005) and now as Director of the Office of Research Trainees (2011-present).

Dr. Penn has served on the Board of Directors of the Canadian Cancer Society and the Canadian Society for Molecular Biosciences. She has also been on several Scientific Advisory Boards and has participated in numerous grant review and awards committees throughout the world. Dr. Penn has received several awards including the New Investigator Award from the Terry Fox Foundation, the Woman-of-Action Award from the Israel Cancer Research Fund, the Award of Distinction from the Leukemia Research Fund, and most recently an Honorary Doctorate from the University of Linkoping, Sweden.  She holds a Canada Research Chair in Molecular Oncology (Tier 1).

Research Synopsis

Cancer occurs when a single cell acquires multiple mutations that result in uncontrolled growth and survival. The tumour cell becomes addicted to these mutations and their activated signalling pathways. Our goal is to understand, exploit and target these tumour-specific vulnerabilities. Our ideas are simple and relevant, and our approach is novel and achievable. We focus on two major areas of research.

Regulation and function of the MYC oncogene. Myc is deregulated in >50% of human cancers and functions as a regulator of gene transcription. We are identifying the target genes regulated by Myc, the cofactors recruited by Myc and the post-translational modifications regulating these processes. Targeting Myc’s potent transforming activity through the development of novel inhibitors is a major
area of investigation. To achieve these goals we use state of the art technologies, including BioID, high-throughput functional analyses, ChIP-seq as well as RNA-seq, and have established several tissue culture and animal models for our work, including leukemia, neuroblastoma and breast cancers. Most recently, we have identified the first Myc-protein interactome and discovered novel regulatory mechanisms critical for Myc to drive cancer initiation and progression.

Exploiting tumour metabolism and statins as anti-cancer agents. Statins are a family of drugs used routinely in the control of hypercholesterolemia that we and others, have shown can trigger tumour-specific cell death. Statins block the rate-limiting enzyme of the mevalonate pathway, which is a basic biochemical pathway essential for cellular metabolism. Because statins are an approved drug for use in humans, we can immediately fast-track statins to impact patient care. To this end, our research goals are to understand why certain tumour-types are highly sensitive to statin-induced apoptosis and how best to use statins in combination treatment. Tumour types under study include leukemia, multiple myeloma, pancreatic, breast and prostate cancers, however, several others neoplasias are also potential targets. Most recently, we have discovered that blocking the restorative feedback response to statins potentiates statin action and this can be achieved by combining statins with another approved agent, dipyridamole. In addition to our research in the lab, we are collaborating with Clinical Scientists to conduct clinical trials to evaluate the efficacy and mechanism of statins as anti-cancer agents.

Recent Publications

• Kalkat, M., Resetca, D., Lourenco, C., Chan, P.K., Wei, Y., Shiah, YJ., Vitkin, N., Tong, Y., Sunnerhagen, M., Done, SJ., Boutros, PC., Raught, B.,Penn, LZ. MYC protein interactome profiling reveals functionally distinct regions that cooperate to drive tumorigenesis. Molecular Cell. 2018 Dec 6;72(5):836-848.
• Tu, WB., Shiah, Y-J., Lourenco, C., Dingar, D., Redel, C., Tamachi, A., Ba-Alawi, W., Aman, A., Al-Awar, R., Cescon, D., Haibe-kains, B., Arrowsmith, C., Raught, B., Boutros, PC., Penn, LZ. MYC interacts with the G9a histone methyltransferase to drive transcriptional repression and tumorigenesis. Cancer Cell. 2018 Oct 8;34(4):579-595.
• Dingar, D., Tu, W., Resetca, D., Lourenco, C., Tamachi, A., De Melo, J., Houlahan, KE., Kalkat, M., Chan, P-K., Boutros, PC., Raught, B., Penn, LZ. MYC dephosphorylation by the PP1/PNUTS phosphatase complex regulates chromatin binding and protein stability. Nature Communications. 2018 Aug 29:9(1): 3502.
• Yu, R, Longo, J., van Leeuwen, J.E., Mullen, P.J., Ba-Alawi, W., Haibe-Kains, B., Penn, L.Z. Statin-induced cancer cell death can be mechanistically uncoupled from prenylation of RAS family proteins. Cancer Res. 2018 Mar 1;78(5):1347-1357. doi: 10.1158/0008-5472.CAN-17-1231. Epub 2017 Dec 11.
• Mullen, PJ., Yu, R., Longo, J., Archer, MC., Penn, LZ. The interplay between cell signalling and the mevalonate pathway in cancer. Nat Rev Cancer. 2016 Nov;16(11):718-731.
• Pandyra, AA., Mullen, PJ., Goard, CA., Ericson, E., Sharma, P., Kalkat, M., Yu, R., Pong, JT., Brown, KR., Hart, T., Gebbia, M., Lang, KS., Giaever, G., Nislow, C., Moffat, J., Penn, LZ. Genome-wide RNAi analysis reveals that simultaneous inhibition of specific mevalonate pathway genes potentiates tumor cell death. Oncotarget. 2015 Sep 29;6(29):26909-21.
• Pandyra, A., Mullen, P., Kalkat, M., Yu, R., Pong, J., Li, Z., Trudel S., Lang, K.S., Minden, M., Schimmer, A., Penn, L.Z. Immediate utility of two approved agents to target both the metabolic mevalonate pathway and its restorative feedback loop. Cancer Research 2014 Sep 1;74(17):4772-82.

Honours and Awards

Honorary Doctor of Medicine, Linkoping University, Sweden
2015 – Present   

Honorary Professor, Tongji Medical University, Wuhan, P.R. China
1996 – Present

Canada Research Chair in Molecular Oncology
2007 – Present  

Woman in Action Award, Israel Cancer Research Fund
2004

Award of Distinction - Leukemia Research Fund
1993

Terry Fox New Investigator Award
1990 – 1993

Graduate Students

Jenna Van Leeuwen
Joseph Longo
Corey Lourenco
Alannah MacDonald (co-supervised with Brian Raught)
Cornelia Redel
Diana Resetca (co-supervised with Brian Raught)
Jason DeMelo - Postdoctoral Fellow
Mohamad Elbaz - Postdoctoral Fellow
Mohamed Kamal - Postdoctoral Fellow
Yong Wei - Postdoctoral Fellow