Pancreatic cancer, cancer stem cells, circulating tumor cells, precision medicine
Our research efforts center on large-scale and high-resolution interrogation of (metastatic) cancer stem cells in their natural microenvironment using functional genetics. We use valuable fresh patient material, single-cell omics technologies, and complementary approaches for functional taxonomy of cancer stem cells. This will define the landscape of stemness and therapeutic resistance via non-genetic evolution in cancer stem cells and provide the basis for developing novel, more effective treatment strategies.
The three overarching high-level objectives of our research program are:
1. Identify and validate novel and common targets that are vital for cancer stem cell functions, specifically focusing on the Chinese patient population.
2. Develop multimodal therapeutic strategies to jointly eliminate cancer stem cells, differentiated cancer cells and the protective stroma.
3. Test these novel treatment strategies using precision medicine approaches.
The underlying hypothesis for our research program is that comprehensive functional interrogation of cancer stem cells results in the identification of novel targets with broad applicability. Inhibition of these newly defined pathways will reduce CSC content and thus prevent tumor relapse during/following treatment.
Significant funds provided by the SJTU School of Medicine and the Shanghai Government have been invested to bring Prof Heeschen and his team to the Center for Single-Cell Omics. We are looking for skilled, professionals and academic personal at all levels:
● Assistant and Associate Professors
● Postdocs (https://www.shsmu.edu.cn/rlzy/info/1011/1728.htm)
● PhD students
● Master students
Available projects are focusing on:
● Dissecting the heterogeneity of (circulating) cancer cells at single-cell level;
● Epigenetic regulation of cancer stem cells using multiomics approaches (e.g. scNMT-seq, CITE-seq)
● Studying the genetic and epigenetic evolution resulting in resistance to therapy;
● Studying the distinct metabolism of (metastatic) cancer stem cells at single-cell resolution;
● Identifying novel therapeutic targets using single-cell functional genomics;
● Identification of novel immune targets for cancer (stem) cells;
● Designing and testing novel immunotherapies (e.g. tunable CAR T-cell) and CSC-targeting therapies;
● Developing an ex vivo precision medicine platform for cancers with unmet medical need;
● Early detection of pancreatic cancer using single-cell omics technology
For inquiries, please contact me at firstname.lastname@example.org
The program has also funded the purchase of intestines suites of equipment, including cutting-edge facilities for the isolation, handling and propagation of rare (circulating) cancer stem cells, and their subsequent comprehensive molecular and phenotypic analysis.
Pancreatic cancer still has the worst outcome of any cancer in China and the world. At the same time, the incidence of pancreatic cancer keeps increasing, with currently ~448,000 new cases in 2019. This number is predicted to further increase in the coming years. Due to its extreme lethality with no effective treatments available at present, pancreatic cancer is currently the 3rd most frequent cause of cancer-related deaths, but may even become the 2nd most frequent cause by 2030.
Pancreatic tumors are heterogeneous, not only because of diverse subclones that arise during tumor evolution, but also because they are driven by functional heterogeneity within each subclone. So-called cancer stem cells (CSC) are responsible for intraclonal functional heterogeneity.
My lab and others have provided conclusive evidence, down to single cells, that cancer stem cells represent the root of the disease, by giving rise to all differentiated progenies within each cancer subclone. These cells are also key elements during tumor dissemination and represent an important cause of disease relapse. We now need to further advance our understanding of cancer stem cell biology as a prerequisite for the development of more efficient therapies that also target these highly tumorigenic cells.
Using cutting-edge technologies developed in our own lab, we are systematically identifying common regulators that control stemness, metabolism and immune privilege in pancreatic cancer. The ultimate goal of our research relies on the development of new multimodal treatment regimens that generate rapid and significant impact on pancreatic cancer progression (i.e. doubling or greater in the median survival for pancreatic cancer patients).
Using single-cell technology, we are building comprehensive molecular portraits of cancer stem cells, at the genetic, transcriptomic proteomic, and metabolomic level. This information is integrated by bioinformatic modelling and subsequently interrogated using in vitro and in vivo functional genomics. The continuous accumulation of new data is feeding back into the modelling process and helps improving the fitness of our CSC model. We have already identified (and validated) various new candidate genes, many of them suitable for further clinical development.
Our studies are directly relevant to improving therapy in pancreatic cancer. We will provide vital and novel information on how to efficiently target cancer stem cells, and, in collaboration with Prof Bai-Yong SHEN at Ruijin Hospital, translate our findings into the clinic, by providing thorough scientific evidence for the design of Phase I-II precision medicine trials, CSC-centered and circCSC-guided. This will directly address and improve the still devastating prognosis of pancreatic cancer patients.
M Agerbæk, …, C Heeschen. Nature Comm 2018 (57 citations)
I Miranda, …, C Heeschen. Nature Methods 2015 (372 citations)
B Sainz, …, C Heeschen. Cancer Cell 2014 (215 citations)
E Lonardo, …, C Heeschen. Cell Stem Cell 2013 (516 citations)
PC Hermann, ... C Heeschen. Cell Stem Cell 2007 (2,807 citations)
C Heeschen, ... Nature Medicine 2003 (1,618 citations)
C Heeschen, ..., CW Hamm NEJM 2003 (1,123 citations)
C Heeschen, ... Nature Medicine 2001 (839 citations)
C Heeschen*,CW Hamm*, ... NEJM 1999 (884 citations)
CW Hamm*, C Heeschen*, ... NEJM 1997 (1,387 citations)
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Prof Heeschen’s Biography
Prof Heeschen was born in Kiel (Germany) and obtained his MD in 1997 at the Free University of Berlin (Germany). His clinical training in Internal Medicine ran from 1996 – 2004 at the University of Hamburg and the University of Frankfurt. During this time, he also spent 2.5 years at the Falk Cardiovascular Research Center at Stanford University (USA) where he worked on basic and translational aspects of angiogenesis and vasculogenic stem cells and subsequently obtained his PhD in 2003.
Prof Heeschen became an independent investigator in 2004 as Professor of Experimental Oncology and Transplantation and Head of the Department of Experimental Medicine at Ludwig-Maximilian-University in Munich (Germany). In 2008, he moved to the Spanish National Cancer Research Centre (CNIO) as a founding member of the Clinical Research Programme. In 2013, he became the lead of the new Centre for Stem Cells in Cancer & Ageing at Barts Cancer Institute, London, UK. In October 2019, Prof Heeschen was recruited to Shanghai Jiao Tong University to establish his translational research program at the Center for Single-Cell Omics.
Prof Heeschen has published more than 150 articles in prestigious scientific journals such as the New England Journal of Medicine, Nature Medicine, The Lancet, Cancer Cell, Cell Stem Cell, the Journal of Experimental Medicine, and PNAS, among others. His work has been cited 30,000 times. Prof Heeschen has made seminal contributions to the field of stem and vascular cell biology that have advanced our understanding of the basic processes of stem cell function and trafficking. His research has been recognized through numerous international awards and has earned him two successive ERC Advanced Investigator Grants for pancreatic cancer research.