Computational Biology and Integrative Genomics of Cancer

FlorenceCavalli_DSC9777

Florence Cavalli Cheffe d'équipe Tel:

Team Overview

Transcriptional deregulation is a critical aspect of cancer biology, that affects tumor initiation, maintenance, response to treatment and recurrence. Indeed, the transcriptional program responsible for development and cell type diversity is also responsible for cancer cell states. This program is controlled by master transcriptional regulators that drive genes’ transcriptional output. We study transcriptional (de)regulation and cancer master transcriptional regulators in two major contexts: (i) temporal heterogeneity specifically in the setting of recurrent disease and (ii) intra-tumoral heterogeneity. These types of heterogeneity are of critical clinical importance since they represent two major causes of treatment failure. The few studies performed on treatment resistant recurrences showed that they are highly genetically different from the matched untreated diagnostic samples. In addition, intra-tumoral heterogeneity studies focused on genetic events have shown significant geographical heterogeneity across several tumor types. However, despite the identification of genetic and epigenetic events with spatial and temporal disparity, the heterogeneity at the level of master regulators, that drive cancer from ontogeny through to oncogenesis is unknown and the specific driver pathways resulting in treatment resistance have proved elusive. An improved understanding of the transcriptional program and especially of the master regulators driving the cancer-specific programs is therefore of critical importance.

In order to decipher mechanisms of resistance, we focus on the master regulators that drive transcriptional output. An understanding of the temporal changes in transcriptional programs is a powerful tool to understand tumor evolution and treatment resistance. We analyse and perform integrative studies of NGS data, single-cell data and clinical information from patient samples to increase our understanding of tumor heterogeneity and resistance to treatment especially in high-grade gliomas.

Postdoctoral position available

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Key publications

Year of publication 2021

Richards LM*, Whitley OKN*, MacLeod G, Cavalli FMG, Coutinho FJ, Jaramillo JE, Svergun N, Riverin M, Croucher DC, Kushida M, Yu K, Guilhamon P, Rastegar N, Ahmadi M, Bhatti JK, Bozek DA, Li N,  Lee L, Che C, Luis E, Park NI, Spears J, Cusimano MD, Das S, Bernstein M, Haibe-Kains B, Lupien M, Luchman HA, Weiss S, Angers S, Dirks PB, Bader GD, Pugh TJ.

Gradient of developmental and injury-response transcriptional states define functional vulnerabilities underpinning glioblastoma heterogeneity.

Nature Cancer2021, 2:157–173. doi:10.1038/s43018-020-00154-9

Skowron P*, Farooq H*, Cavalli FMG*, Morrissy AS*, Ly M, Hendrikse LD, Wang EY, Djambazian H, Zhu H, Mungall KL, Trinh QM, Zheng T, Dai S, Stucklin ASG, Vladoiu MC, Fong V, Holgado BL, Nor C, Wu X, Abd-Rabbo D, Bérubé P, Wang YC, Luu B, Suarez RA, Rastan A, Gillmor AH, Lee JJY, Zhang XY, Daniels C, Dirks P, Malkin D, Bouffet E, Tabori U, Loukides J, Doz FP, Bourdeaut F, Delattre OO, Masliah-Planchon J, Ayrault O, Kim SK, Meyronet D, Grajkowska WA, Carlotti CG, de Torres C, Mora J, Eberhart CG, Van Meir EG, Kumabe T, French PJ, Kros JM, Jabado N, Lach B, Pollack IF, Hamilton RL, Rao AAN, Giannini C, Olson JM, Bognár L, Klekner A, Zitterbart K, Phillips JJ, Thompson RC, Cooper MK, Rubin JB, Liau LM, Garami M, Hauser P, Li KKW, Ng HK, Poon WS, Yancey Gillespie G, Chan JA, Jung S, McLendon RE, Thompson EM, Zagzag D, Vibhakar R, Ra YS, Garre ML, Schüller U, Shofuda T, Faria CC, López-Aguilar E, Zadeh G, Hui CC, Ramaswamy V, Bailey SD, Jones SJ, Mungall AJ, Moore RA, Calarco JA, Stein LD, Bader GD, Reimand J, Ragoussis J, Weiss WA, Marra MA, Suzuki H, Taylor MD.

The transcriptional landscape of Shh medulloblastoma.

Nature Communications, 12(1):1749. doi: 10.1038/s41467-021-21883-0.

Year of publication 2018

Cavalli FMG*, Hübner JM*, Sharma T*, Luu B, Sill M, Zapotocky M, Mack SC, Witt H, Lin T, Shih DJH, Ho B, Santi M, Emery L, Hukin J, Dunham C, McLendon RE, Lipp ES, Gururangan S, Grossbach A, French P, Kros JM, van Veelen MC, Rao AAN, Giannini C, Leary S, Jung S, Faria CC, Mora J, Schüller U, Alonso MM, Chan JA, Klekner A, Chambless LB, Hwang EI, Massimino M, Eberhart CG, Karajannis MA, Lu B, Liau LM, Zollo M, Ferrucci V, Carlotti C, Tirapelli DPC, Tabori U, Bouffet E, Ryzhova M, Ellison DW, Merchant TE, Gilbert MR, Armstrong TS, Korshunov A, Pfister SM, Taylor MD, Aldape K, Pajtler KW, Kool M, Ramaswamy V.

Heterogeneity within the PF-EPN-B ependymoma subgroup.

Acta Neuropathologica, 136(2):227-237. doi: 10.1007/s00401-018-1888-x

Year of publication 2017

Cavalli FMG*, Remke M*, Rampasek L, Peacock J, Shih DJH, Luu B, Garzia L, Torchia J, Nor C, Morrissy AS, Agnihotri S, Thompson YY, Kuzan-Fischer CM, Farooq H, Isaev K, Cho B-K, Kim S-K, Wang K-C, Lee JY, Grajkowska WA, Perek-Polnik M, Vasiljevic A, Faure-Conter C, Jouvet A, Giannini C, Nageswara Rao AA, Li KWK, Ng H-K, Eberhart CG, Pollack IF, Hamilton RL, Gillespie GY, Olson JM, Leary S, Weiss WA, Lach B, Chambless LB, Thompson RC, Cooper MK, Vibhakar R, Hauser P, van Veelen M-LC, Kros JM, French PJ, Shin Ra Y, Kumabe T, López-Aguilar E, Zitterbart K, Sterba J, Finocchiaro G, Massimino M, Van Meir EG, Osuka S, Shofuda T, Klekner A, Zollo M, Leonard JR, Rubin JB, Jabado N, Albrecht S, Mora J, Van Meter TE, Jung S, Moore AS, Hallahan AR, Chan JA, Tirapelli DPC, Carlotti CG, Fouladi M, Pimentel J, Faria CC, Saad, AG, Massimi L, Liau LM, Wheeler H, Nakamura H, Elbabaa SK, Perezpeña-Diazconti M, Ponce de León FC, Robinson S, Zapotocky M, Lassaletta A, Huang A, Hawkins CE, Tabori U, Bouffet E, Bartels U, Dirks P, Rutka JT, Bader GD, Reimand J, Goldenberg A, Ramaswamy V, Taylor MD.

Intertumoral heterogeneity within medulloblastoma subgroups,

Cancer Cell, 31(6): 737-754. doi: 10.1016/j.ccell.2017.05.005

Morrissy AS*, Cavalli FMG*, Remke M*, Ramaswamy V, Shih DJH,Holgado BL, Farooq H, Donovan LK, Garzia L, Agnihotri S, Kiehna EN, Mercier E, Mayoh C, Papillon-Cavanagh S, Nikbakht H, Gayden T, Torchia J, Picard D, Merino DM, Vladoiu M, Luu B, Wu X, Daniels C, Horswell S, Thompson YY, Hovestadt V, Northcott PA, Jones DTW, Peacock J, Wang X, Mack SC, Reimand J, Albrecht S, Fontebasso AM, Thiessen N, Li Y, Schein JE, Lee D, Carlsen R, Mayo M, Tse K, Tam A, Dhalla N, Ally A, Chuah E, Cheng Y, Plettner P, Li HI, Corbett RD, Wong T, Long W, Loukides J, Buczkowicz P, Hawkins CE, Tabori U, Rood BR, Myseros JS, Packer RJ, Korshunov A, Lichter P, Kool M, Pfister SM, Schüller U, Dirks P, Huang A, Bouffet Eric, Rutka JT, Bader GD, Swanton C, Ma Y, Moore RA, Mungall AJ, Majewski J, Jones SJM, Das S, Malkin D, Jabado N, Marra MA, Taylor MD.

Spatial heterogeneity in medulloblastoma

Nature Genetics, 49(5): 780-788. doi: 10.1038/ng.3838

*Shared co-first author

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