Cancer Genetics and Functional Genomics

Prof Ron Firestein leads the Cancer Genetics and Functional Genomics lab, and the Next Generation Precision Medicine program at Hudson Institute.

Research Group

Overview

The work of the Cancer Genetics and Functional Genomics Research group, directed by Professor Ron Firestein, is focused on using functional and integrated genomic approaches to understanding the basic underpinnings of cancer. Major themes in the lab are

Integrative genomic approaches to identify new oncogenic drivers in cancer. The Cancer Genetics and Functional Genomics lab has undertaken sophisticated integrative genomic analyses of colorectal, lung and breast cancers. Using innovative functional genomic screens (CRISPR, shRNA/siRNA) the team has uncovered a number of novel oncogenic drivers and dissected their mechanistic input into cancer signalling pathways. Importantly, two of these targets have led to novel small molecule programs that are currently in drug development (CDK8 and LDHB).
Identification and characterisation of Wnt pathway regulators in colon cancer. While a post-doc at Dana Farber Cancer Institute, Prof Firestein identified CDK8 as a colon cancer oncogene that regulates the Wnt/b-catenin pathway (Firestein R. et al Nature 2008). Since then, the Cancer Genetics and Functional Genomics lab has developed mouse models and in vivo systems to characterise the function of CDK8 and its paralog, CDK19, in normal homeostasis, development and cancer progression. The team has also collaborated with other groups to develop targeted therapies to upstream regulators of the Wnt pathway.
Elucidation of novel cancer therapeutic biomarkers in preclinical models and clinical samples. The lab’s recent work has identified an important role for enhancer mediated transcripts, i.e. eRNAs, as biomarkers for distinct cancer states and predicting therapeutic response. We are now working to systematically characterise eRNA function and expression in tumours using state of the art genomic editing technologies.

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Diseases we research

Research Group Head | Professor Ron Firestein

There is an urgent need for new and more precisely targeted medicines to treat childhood cancers. My work uses functional and integrated genomic approaches to understanding the basic underpinnings of cancer and identifying treatment options to target them.

Meet the team

News from the lab

21 February 2024

Curing childhood cancer: all roads lead to Melbourne

See more news articles about Cancer Genetics and Functional Genomics

Student opportunities

Publication highlights

Sun CX, Daniel P, Bradshaw G, Shi H, Loi M, Chew N, Parackal S, Tsui V, Liang Y, Koptyra M, Adjumain S, Sun C, Chong WC, Fernando D, Drinkwater C, Tourchi M, Habarakada Dilru, Sooraj D, Carvalho D, Storm PB, Baubet V, Sayles LC, Fernandez E, Nguyen T, Pörksen M, Doan Anh, Crombie D, Panday M, Zhukova N, Dun MD, Ludlow LE, Day B, Stringer B, Neeman N, Rubens J, Hutton Raabe E, Vinci M, Tyrrell V, Fletcher JI, Ekert PG, Dumevska B, Ziegler DS, Tsoli M, Syed Sulaiman NF, Loh AHP, Low SYY, Sweet-Cordero EA, Monje M, Resnick A, Jones C, Downie P, Williams B, Rosenbluh J, Gough D, Cain JE, Firestein R (2023) Generation and Multi-Dimensional Profiling of a Childhood Cancer Cell Line Atlas Defines New Therapeutic Opportunities. Cancer Cell, 41:660-677.e7.
Dannappel MV, Zhu D, Sun X, Chua HK, Poppelaars M, Suehiro M, Khadka S, Lim Kam Sian TC, Sooraj D, Loi M, Gao H, Croagh D, Daly RJ, Faridi P, Boyer T, Firestein R (2022) CDK8 and CDK19 regulate intestinal differentiation and homeostasis via the chromatin remodeling complex SWI/SNF. J Clin Invest, 132:e158593.
Sooraj D, Sun C, Doan A, Garama DJ, Dannappel MV, Zhu D, Chua HK, Mahara S, Wan Hassan WA, Tay YK, Guanizo A, Croagh D, Prodanovic Z, Gough DJ, Wan C, Firestein R (2022) MED12 and BRD4 Cooperate to Sustain Cancer Growth Upon Loss of Mediator Kinase. Mol Cell, 82:123-139.e7.
Wan C, Mahara S, Sun C, Doan A, Chua H, Xu D, Bian J, Li Y, Sooraj D, Cierpicki T, Grembecka J, Firestein R (2021) Genome-scale CRISPR-Cas9 screen of Wnt/β-catenin signalling identifies therapeutic targets for Colorectal Cancer. Sci Adv, 7:eabf2567, 2021.
Adler AS, McCleland ML, Yee S, Yaylaoglu M, Hussain S, Cosino E, Quinones G, Modrusan Z, Seshagiri S, Torres E, Chopra VS, Haley B, Zhang Z, Blackwood EM, Singh M, Junttila M, Stephan JP, Liu J, Pau G, Fearon ER, Jiang Z, Firestein R (2014) An integrative analysis of colon cancer identifies an essential function for PRPF6 in tumor growth. Genes Dev, 28:1068-1084.
Liu J, McCleland M, Stawiski EW, Gnad F, Mayba O, Haverty PM, Durinck S, Chen YJ, Klijn C, Jhunjhunwala S, Lawrence M, Liu H, Wan Y, Chopra V, Yaylaoglu MB, Yuan W, Ha C, Gilbert HN, Reeder J, Pau G, Stinson J, Stern HM, Manning G, Wu TD, Neve RM, de Sauvage FJ, Modrusan Z, Seshagiri S, Firestein R, Zhang Z (2014) Integrated exome and transcriptome sequencing reveals ZAK isoform usage in gastric cancer. Nature Commun, 5:3830.
Adler AS, McCleland ML, Truong T, Lau S, Modrusan Z, Soukup TM, Roose-Girma M, Blackwood EM, Firestein R (2012) CDK8 maintains tumor dedifferentiation and embryonic stem cell pluripotency. Cancer Res, 72:2129-39.
Firestein R, Hahn WC (2009) Revving the throttle on an oncogene: CDK8 takes the driver seat. Cancer Res, 69:7899-901.
Firestein R, Bass AJ, Kim SY, Dunn IF, Silver SJ, Guney I, Freed E, Ligon AH, Vena N, Ogino S, Chheda MG, Tamayo P, Finn S, Shrestha Y, Boehm JS, Jain S, Bojarski E, Mermel C, Barretina J, Chan JA, Baselga J, Tabernero J, Root DE, Fuchs C, Loda M, Shivdasani RA, Meyerson M, Hahn WC (2008) CDK8 is a colorectal cancer oncogene that regulates beta-catenin activity. Nature, 455:547-51.

Our research group is keen to discuss funding opportunities

Support our research

Cancer Genetics and Functional Genomics

Overview

Diseases we research

Research Group Head | Professor Ron Firestein

Meet the team

News from the lab

Funding turbocharges search for children’s brain cancer cure

NHMRC Investigator Grants 2023

2023 Science Innovation Seed Funding Awards

Conquering childhood cancer | Eli’s story

2023 Harold Mitchell Travel Fellowships

Victorian government funds paediatric cancer research

Surviving childhood cancer – Luca’s story

Curing childhood cancer: all roads lead to Melbourne

Student opportunities

Publication highlights

Our research group is keen to discuss funding opportunities