Logan Walsh, Ph.D
Rosalind and Morris Goodman Cancer Research Centre
Department of Human Genetics
The Walsh lab uses both experimental and computational approaches to understand the genetic basis of cancer. Lung cancer is responsible for over 25% of all cancer related deaths. One in twelve Canadians will develop lung cancer during his/her lifetime and more people die from lung cancer than breast, colorectal, and prostate cancer combined. The Walsh lab is focused on translational research questions, as we foster close collaborations between physicians and scientists to address clinically relevant challenges.
Some ongoing projects include:
1. Assignment of patients with lung cancer to the variety of available conventional and novel therapeutics such as immunotherapy is currently informed by highly rudimentary data. As a result, predicting response rates to conventional systemic therapy, single or multi-target immunotherapy or combinatorial approaches is difficult and may lead to sub-optimal patient outcomes both regarding response and toxicity. The lab uses next-generation sequencing technology to define how and when, amongst the available armamentarium of systemic therapies, which are optimally utilized by delineating their mechanisms and the contexts within which they perform best.
2. Despite metastasis being the leading cause of cancer‐related death, we lack a unifying understanding of the large‐scale phenotypic reprogramming underlying metastatic disease. While several genes that are sufficient to induce metastatic progression have been identified, there is untapped value in the systematic identification of genes that are more universally necessary for progression, as valuable therapeutic targets. The Walsh lab interrogates cancer specific transcriptional interaction networks to elucidate the transcriptional control structures causally responsible for regulating genetic programs activated during primary tumor transition to metastases.
3. The CRISPR/Cas9 system is an invaluable tool for engineering a wide variety of genetic alterations. The Walsh lab develops novel CRISPR/Cas9 models that will be used in combination with high-throughput computational strategies to screen for therapeutic targets in lung, brain and ovarian cancers.
Walsh LA, Alvarez MJ, Sabio EY, Reyngold M, Makarov V, Mukherjee S, Lee KW, Desrichard A, Turcan S, Dalin MG, Rajasekhar VK, Chen S, Vahdat LT, Califano A, Chan TA. An Integrated Systems Biology Approach Identifies TRIM25 as a Key Determinant of Breast Cancer Metastasis. Cell Reports (2017). PubMed
Quail DF, Olson OC, Bhardwaj P, Walsh LA, Akkari L, Quick ML, Chen IC, Wenden N, Ben-Chetrit N, Walker J, Holt PR, Dannenberg AJ & Joyce JA. Obesity alters the lung myeloid cell landscape to enhance breast cancer metastasis through IL5 and GM-CSF. Nature Cell Biology (2017). PubMed
*Roy DM, *Walsh LA, Desrichard A, Huse JT, Wu W, Gao J, Bose P, Lee W, Chan TA *co-first authorship. Integrated Genomics for Pinpointing Survival Loci within Arm-Level Somatic Copy Number Alterations. Cancer Cell (2016). PubMed
Riaz N, Havel JJ, Kendall SM, Makarov V, Walsh LA, Desrichard A, Weinhold N, Chan TA.
Recurrent SERPINB3 and SERPINB4 mutations in patients who respond to anti-CTLA4
immunotherapy. Nature Genetics (2016). PubMed
Walsh LA, Roy DM, Reyngold M, Giri D, Snyder A, Turcan S, Badwe CR, Lyman J, Bromberg J, King TA, Chan TA. RECK controls breast cancer metastasis by modulating a convergent, STAT3-dependent neoangiogenic switch. Oncogene (2015). PubMed
Snyder A, Makarov V, Merghoub T, Yuan J, Zaretsky JM, Desrichard A, Walsh LA, Postow MA, Wong P, Ho TS, Hollmann TJ, Bruggeman C, Kannan K, Li Y, Elipenahli C, Liu C, Harbison CT, Wang L, Ribas A, Wolchok JD, Chan TA. Genetic basis for clinical response to CTLA-4 blockade in melanoma. The New England Journal of Medicine (2014). PubMed
Ho AS, Kannan K, Roy DM, Morris LG, Ganly I, Katabi N, Ramaswami D, Walsh LA, Eng S, Huse JT, Zhang J, Dolgalev I, Huberman K, Heguy A, Viale A, Drobnjak M, Leversha MA, Rice CE, Singh B, Iyer NG, Leemans CR, Bloemena E, Ferris RL, Seethala RR, Gross BE, Liang Y, Sinha R, Peng L, Raphael BJ, Turcan S, Gong Y, Schultz N, Kim S, Chiosea S, Shah JP, Sander C, Lee W, Chan TA. The mutational landscape of adenoid cystic carcinoma. Nature Genetics (2013). PubMed
*Turcan S , *Rohle D , *Goenka A , Walsh LA , Fang F , Yilmaz E , Campos C , Fabius AW , Lu C , WardPS , Thompson CB , Kaufman A , Guryanova O , Levine R , Heguy A , Viale A , Morris LG , Huse JT , Mellinghoff IK , Chan TA *Equal first Authorship. IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype. Nature (2012). PubMed
Morris L, Kaufman A, Gong Y,*Walsh LA, Turcan S, Eng S, Kanan K, Zou Y, Peng L., Banuchi V, Paty P, Vakiani E, Solit D, Zeng Z,Singh B, Ganly I, Liau L, Cloughesy P, Mischel P, Mellinghoff I, Chan T. Frequent mutation of the Drosophila tumor suppressor-related gene FAT1 in multiple human cancers leads to aberrant Wnt activation. Nature Genetics (2012). PubMed