KPC tumor pSMAD2 ECAD

Our Laboratory focuses on identifying more effective cancer treatments for pancreatic ductal adenocarcinoma (PDA) patients that are based on the biological mechanisms that drive cancer.

In particular, our research focuses on:

  1. Characterizing fibroblast and immune cell heterogeneity in normal, inflamed and malignant states.
  2. Pharmacologically and genetically dissecting cancer/fibroblast signaling interactions.
  3. Developing therapeutic strategies that target tumor-promoting stromal components of PDA.

Vacancies

Research Associate (Fixed Term)
Deadline: 11 August 2019

Research Assistant (Fixed Term)
Deadline: 11 August 2019

About Giulia

I received my Master’s degree in Biomolecular Sciences and Genetics from the University of Pavia, Italy. My Ph.D. dissertation was completed with Sir Shankar Balasubramanian at the Cancer Research UK Cambridge Institute. During my doctoral training, I demonstrated the existence of RNA and DNA secondary structures called G-quadruplexes in human cells by developing a G-quadruplex-specific antibody. This antibody has become a standard tool for the study of these structures in homeostasis and cancer.

During my post-doctoral training, I furthered my interest in characterizing the biochemical differences between normal and malignant cells by studying the signaling pathways active in the microenvironment of pancreatic ductal adenocarcinoma (PDA). In particular, using organoid and mouse models, I investigated the crosstalk between cancer cells and cancer-associated fibroblasts (CAFs). I co-led the establishment of a three-dimensional co-culture system of PDA organoids and fibroblasts, which recapitulated the extracellular matrix deposition and symbiotic interactions observed in vivo. Using this co-culture system and mouse models of PDA, I helped to identify two distinct CAF subtypes, with potentially different roles in PDA progression. I also demonstrated that these cell populations dynamically interconvert, depending upon spatial and tropic cues. Importantly, this cell plasticity represents a therapeutic opportunity as it may be more beneficial to convert, rather than just ablate, tumor-promoting CAFs into potentially tumor-restraining populations. In addition, I determined the critical ligands and receptors responsible for specifying these CAF subtypesin vitroand in vivo, laying the groundwork for the generation of new models that will allow to genetically dissect the roles of these populations.

Contact: gbiffi@cshl.edu and Giulia.Biffi@cruk.cam.ac.uk 

EM image of organoids.
GFP organoids-PSCs mCherry coculture.

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Teaching experience

2016 – Teaching assistant for the CSHL Course “Organotypic and next Generation culture methods”
2018 – Instructor for the CSHL Course “Organotypic culture methods”
2019 – Teaching Assistant and Lecturer at the CSHL Workshop on Pancreatic Cancer

Awards

11/18 – Cancer Center Trainee Travel Award, CSHL In-House symposium
11/18 – Poster prize awarded from the WSBS at CSHL, CSHL In-House symposium
10/17 – Ghislieri Prize 2017
06/15 – Human Frontier Science Program fellowship
12/14 – EMBO long-term fellowship
11/13 – International Prize NorthSouth Pescarabruzzo Foundation 2013
07/13 – Commencement speaker at the graduation ceremony at the University of Pavia, Italy

Selected publications

Biffi G., Tannahill D. McCafferty J. and Balasubramanian S. Quantitative Visualization of DNA G-quadruplex Structures in Human Cells. Nature Chem 5, 182-6 (2013). Publication highlighted in several international newspapers including BBC news (http://www.bbc.co.uk/news/science-environment-21091066).

Biffi G., Di Antonio M., Tannahill D. and Balasubramanian S. Visualization and Selective Chemical Targeting of RNA G-quadruplex Structures in the Cytoplasm of Human Cells. Nature Chem 6, 75-80 (2014).

Boj SF.*, Hwang C-I.*, Baker LA.*, Chio IIC.*, Engle DD.*, Corbo V.*, Jager M.*, Ponz-Sarvise M., Tiriac H., Spector MS., Gracanin A., Oni T., Yu KH., van Boxtel R., Huch M., Rivera KD., Wilson JP., Feigin ME., Ohlund D., Handly-Santana A., Ardito-Abraham CM., Ludwig M., Elyada E., Alagesan B., Biffi G., Yordanov GN., Delcuze B., Creighton B., Wright K., Park Y., Morsink FHM., Molenaar IQ., Rinkes IHB., Cuppen E., Hao Y., Jin Y., Nijman IJ., Iacobuzio-Donahue C., Leach SD., Pappin DJ., Hammell M., Klimstra DS., Basturk O., Hruban RH., Offerhaus GJ., Vries RGJ., Clevers H. and Tuveson DA. Organoid Models of Human and Mouse Ductal Pancreatic Cancer. Cell 160:1–15 (2015).

Daniel Öhlund*, Abram Handly-Santana*, Giulia Biffi*, Ela Elyada*, Ana S. Almeida, Mariano Ponz-Sarvise, Vincenzo Corbo, Tobiloba E. Oni, Stephen A. Hearn, Eun Jung Lee, Iok In Christine Chio, Chang-Il Hwang,Hervé Tiriac, Lindsey A. Baker, Dannielle D. Engle, Mikala Egeblad, Douglas T. Fearon, James M. Crawford, Hans Clevers, Youngkyu Park, and David A. Tuveson. Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer.J Exp Med (2017).

Giulia Biffi and David A. Tuveson. Double trouble for tumours. Nature (2017). (News & Views)

Giulia Biffi and David A. Tuveson. Deciphering cancer fibroblasts. JEM (2018). (Highlight)

Giulia Biffi, Tobiloba E. Oni, Benjamin Spielman, Yuan Hao, Ela Elyada, Youngkyu Park, Jonathan Preall, and David A. Tuveson.IL-1-induced JAK/STAT signaling is antagonized by TGF-bto shape CAF heterogeneity in pancreatic ductal adenocarcinoma. Cancer Discov (2019).

Giulia Biffi and David A. Tuveson. A FATal combination: fibroblast-derived lipids and cancer-derived autotaxin promote pancreatic cancer growth. Cancer Discovery (2019). (In the spotlight)

Elyada, E., Bolisetty, M.*, Laise, P.*, Flynn, W.F.*, Courtois, E.T., Burkhart, R.A., Teinor, J.A., Belleau, P., Biffi, G., Lucito, M.S., Sivajothi, S., Armstrong, T.D., Engle, D.D., Yu, K.H., Hao, Y., Wolfgang, C.L., Park, Y., Preall, J., Jaffee, E.M., Califano, A., Robson, P., & Tuveson D.A. Cross-species single-cell analysis of pancreatic ductal adenocarcinoma reveals antigen-presenting cancer-associated fibroblasts. Cancer Discov (in press).