The Aparicio lab studies the genomic and phenotypic behaviour of breast and other cancers. Integrating leading edge technologies with patient-derived xenograft models of cancer, this research is working to better understand how cancer clones evolve and to identify novel strategies for cancer treatment and predictors of response.   

Dr. Aparicio’s research program encompasses the fields of cancer genomics, cancer evolution, single cell biology, mouse genetic models, high throughput screens, small molecule chemical probe development and translational breast cancer research. His work on the molecular taxonomy of breast cancer led to identification of new genes that could change the way breast cancer is diagnosed, and form the basis of next-generation treatments. This discovery was preceded by another breakthrough in decoding the genetic makeup of the most-deadly form of breast cancer, known as triple negative subtype (TNBC). Dr. Aparicio is also working to develop quantitative measures of clonal fitness in patients, including methods for single cell genome sequencing and PDX models of human cancer. He collaborates widely with other groups, with current projects including the genomic and biochemical analysis of lymphoma, ovarian cancer, and several rare pediatric cancers. He was a co-founder of Paradigm Therapeutics (now, Takeda Cambridge) and currently Contextual Genomics Ltd.

For more information about our teams and projects, please visit our lab website.

Members

Faculty/Leaders

Staff

Shadi Ansari

Microscopy Engineer

Vinci Au

Research Assistant/Technician

Caroline Baril

Research Assistant/Technician

Cherie Bates

Research Project Manager

Sean Beatty

Project Manager - Bioinformatics

Viviana Cerda Llanos

Research Assistant

William Daniels

Research Assistant

Shuyu Fan

Senior Biostatistician

Cynthia Ferguson

Research Projects and Operations Leader

Cristina Flores

Research Assistant/Technician

Benjamin Furman

Bioinformatics Scientist

BaRun Kim

Research Assistant/Technician

Esther Kong

Project Manager - Clinical Studies

Daniel Lai

Senior Bioinformatics Scientist

Joseph Micla

Full Stack Developer

Ciara O'Flanagan, PhD

Research Associate

Benoit Prevost-Potvin

Software Architect

Robert Reinert

Data Manager

Yukta Thapliyal

Programmer

Adrian Wan

Laboratory Research and Operations Manager

Elena Zaikova

Bioinformatics Scientist

Post-Docs

Viktoriia Cherkasova

Postdoctoral Fellow

Hoa Tran

Postdoctoral Fellow

Students/Trainees

Matthew Cho

Co-op Student

Sam Dang

Co-op Student

Eric Lee

Graduate Student

Yi Fei (Eric) Liu

Graduate Student

Cathy Liu

Co-op Student

Ben Roberts

Co-op Student

Evan Wright

Co-op Student

Selected Publications

Clonal Decomposition and DNA Replication States Defined by Scaled Single-Cell Genome Sequencing.

Cell, 2019
Laks, Emma, McPherson, Andrew, Zahn, Hans, Lai, Daniel, Steif, Adi, Brimhall, Jazmine, Biele, Justina, Wang, Beixi, Masud, Tehmina, Ting, Jerome, Grewal, Diljot, Nielsen, Cydney, Leung, Samantha, Bojilova, Viktoria, Smith, Maia, Golovko, Oleg, Poon, Steven, Eirew, Peter, Kabeer, Farhia, Ruiz de Algara, Teresa, Lee, So Ra, Taghiyar, M Jafar, Huebner, Curtis, Ngo, Jessica, Chan, Tim, Vatrt-Watts, Spencer, Walters, Pascale, Abrar, Nafis, Chan, Sophia, Wiens, Matt, Martin, Lauren, Scott, R Wilder, Underhill, T Michael, Chavez, Elizabeth, Steidl, Christian, Da Costa, Daniel, Ma, Yussanne, Coope, Robin J N, Corbett, Richard, Pleasance, Stephen, Moore, Richard, Mungall, Andrew J, Mar, Colin, Cafferty, Fergus, Gelmon, Karen, Chia, Stephen, , , Marra, Marco A, Hansen, Carl, Shah, Sohrab P, Aparicio, Samuel

Dissociation of solid tumor tissues with cold active protease for single-cell RNA-seq minimizes conserved collagenase-associated stress responses.

Genome biology, 2019
O'Flanagan, Ciara H, Campbell, Kieran R, Zhang, Allen W, Kabeer, Farhia, Lim, Jamie L P, Biele, Justina, Eirew, Peter, Lai, Daniel, McPherson, Andrew, Kong, Esther, Bates, Cherie, Borkowski, Kelly, Wiens, Matt, Hewitson, Brittany, Hopkins, James, Pham, Jenifer, Ceglia, Nicholas, Moore, Richard, Mungall, Andrew J, McAlpine, Jessica N, , , Shah, Sohrab P, Aparicio, Samuel

CLK-dependent exon recognition and conjoined gene formation revealed with a novel small molecule inhibitor.

Nature communications, 2017
Funnell, Tyler, Tasaki, Shinya, Oloumi, Arusha, Araki, Shinsuke, Kong, Esther, Yap, Damian, Nakayama, Yusuke, Hughes, Christopher S, Cheng, S-W Grace, Tozaki, Hirokazu, Iwatani, Misa, Sasaki, Satoshi, Ohashi, Tomohiro, Miyazaki, Tohru, Morishita, Nao, Morishita, Daisuke, Ogasawara-Shimizu, Mari, Ohori, Momoko, Nakao, Shoichi, Karashima, Masatoshi, Sano, Masaya, Murai, Aiko, Nomura, Toshiyuki, Uchiyama, Noriko, Kawamoto, Tomohiro, Hara, Ryujiro, Nakanishi, Osamu, Shumansky, Karey, Rosner, Jamie, Wan, Adrian, McKinney, Steven, Morin, Gregg B, Nakanishi, Atsushi, Shah, Sohrab, Toyoshiba, Hiroyoshi, Aparicio, Samuel

CX-5461 is a DNA G-quadruplex stabilizer with selective lethality in BRCA1/2 deficient tumours.

Nature communications, 2017
Xu, Hong, Di Antonio, Marco, McKinney, Steven, Mathew, Veena, Ho, Brandon, O'Neil, Nigel J, Santos, Nancy Dos, Silvester, Jennifer, Wei, Vivien, Garcia, Jessica, Kabeer, Farhia, Lai, Daniel, Soriano, Priscilla, Banáth, Judit, Chiu, Derek S, Yap, Damian, Le, Daniel D, Ye, Frank B, Zhang, Anni, Thu, Kelsie, Soong, John, Lin, Shu-Chuan, Tsai, Angela Hsin Chin, Osako, Tomo, Algara, Teresa, Saunders, Darren N, Wong, Jason, Xian, Jian, Bally, Marcel B, Brenton, James D, Brown, Grant W, Shah, Sohrab P, Cescon, David, Mak, Tak W, Caldas, Carlos, Stirling, Peter C, Hieter, Phil, Balasubramanian, Shankar, Aparicio, Samuel

Divergent modes of clonal spread and intraperitoneal mixing in high-grade serous ovarian cancer.

Nature genetics, 2016
McPherson, Andrew, Roth, Andrew, Laks, Emma, Masud, Tehmina, Bashashati, Ali, Zhang, Allen W, Ha, Gavin, Biele, Justina, Yap, Damian, Wan, Adrian, Prentice, Leah M, Khattra, Jaswinder, Smith, Maia A, Nielsen, Cydney B, Mullaly, Sarah C, Kalloger, Steve, Karnezis, Anthony, Shumansky, Karey, Siu, Celia, Rosner, Jamie, Chan, Hector Li, Ho, Julie, Melnyk, Nataliya, Senz, Janine, Yang, Winnie, Moore, Richard, Mungall, Andrew J, Marra, Marco A, Bouchard-Côté, Alexandre, Gilks, C Blake, Huntsman, David G, McAlpine, Jessica N, Aparicio, Samuel, Shah, Sohrab P

The somatic mutation profiles of 2,433 breast cancers refines their genomic and transcriptomic landscapes.

Nature communications, 2016
Pereira, Bernard, Chin, Suet-Feung, Rueda, Oscar M, Vollan, Hans-Kristian Moen, Provenzano, Elena, Bardwell, Helen A, Pugh, Michelle, Jones, Linda, Russell, Roslin, Sammut, Stephen-John, Tsui, Dana W Y, Liu, Bin, Dawson, Sarah-Jane, Abraham, Jean, Northen, Helen, Peden, John F, Mukherjee, Abhik, Turashvili, Gulisa, Green, Andrew R, McKinney, Steve, Oloumi, Arusha, Shah, Sohrab, Rosenfeld, Nitzan, Murphy, Leigh, Bentley, David R, Ellis, Ian O, Purushotham, Arnie, Pinder, Sarah E, Børresen-Dale, Anne-Lise, Earl, Helena M, Pharoah, Paul D, Ross, Mark T, Aparicio, Samuel, Caldas, Carlos

The clonal and mutational evolution spectrum of primary triple-negative breast cancers.

Nature, 2012
Shah, Sohrab P, Roth, Andrew, Goya, Rodrigo, Oloumi, Arusha, Ha, Gavin, Zhao, Yongjun, Turashvili, Gulisa, Ding, Jiarui, Tse, Kane, Haffari, Gholamreza, Bashashati, Ali, Prentice, Leah M, Khattra, Jaswinder, Burleigh, Angela, Yap, Damian, Bernard, Virginie, McPherson, Andrew, Shumansky, Karey, Crisan, Anamaria, Giuliany, Ryan, Heravi-Moussavi, Alireza, Rosner, Jamie, Lai, Daniel, Birol, Inanc, Varhol, Richard, Tam, Angela, Dhalla, Noreen, Zeng, Thomas, Ma, Kevin, Chan, Simon K, Griffith, Malachi, Moradian, Annie, Cheng, S-W Grace, Morin, Gregg B, Watson, Peter, Gelmon, Karen, Chia, Stephen, Chin, Suet-Feung, Curtis, Christina, Rueda, Oscar M, Pharoah, Paul D, Damaraju, Sambasivarao, Mackey, John, Hoon, Kelly, Harkins, Timothy, Tadigotla, Vasisht, Sigaroudinia, Mahvash, Gascard, Philippe, Tlsty, Thea, Costello, Joseph F, Meyer, Irmtraud M, Eaves, Connie J, Wasserman, Wyeth W, Jones, Steven, Huntsman, David, Hirst, Martin, Caldas, Carlos, Marra, Marco A, Aparicio, Samuel

The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups.

Nature, 2012
Curtis, Christina, Shah, Sohrab P, Chin, Suet-Feung, Turashvili, Gulisa, Rueda, Oscar M, Dunning, Mark J, Speed, Doug, Lynch, Andy G, Samarajiwa, Shamith, Yuan, Yinyin, Gräf, Stefan, Ha, Gavin, Haffari, Gholamreza, Bashashati, Ali, Russell, Roslin, McKinney, Steven, , , Langerød, Anita, Green, Andrew, Provenzano, Elena, Wishart, Gordon, Pinder, Sarah, Watson, Peter, Markowetz, Florian, Murphy, Leigh, Ellis, Ian, Purushotham, Arnie, Børresen-Dale, Anne-Lise, Brenton, James D, Tavaré, Simon, Caldas, Carlos, Aparicio, Samuel

Projects

Tumour heterogeneity and clonal dynamics of breast cancer

Cancer is a dynamic disease, and as a result a single tumour mass may comprise a diverse collection cancer clones with distinct phenotypes, mutations or sensitivity to treatment. Integrating deep and single cell genomic and transcriptomic sequencing with statistical modeling of clonal fitness, our lab is developing methods to study and predict the clonal dynamics of cancer in PDX and cell models, under natural and selective pressures such as drug intervention or CRISPR knockout.

Methods for studying cancers at single cell resolution

Single cell sequencing technologies allow the study of phenomena such as tumour heterogeneity, clonal dynamics, tissue microenvironments as well as the identification of novel and intermediary cell types, which may not be easily resolved with bulk sequencing strategies. Our lab has developed methods for the surveying of single cell genomics, and integrates them with methods to study the epigenome and transcriptome at single cell resolution, as well as with imaging techniques for spatial context

Sponsors

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