Epigenetics of Immunity in Cancer
- Project duration: September 2019 - December 2022
- Project status: ongoing
- Funding: Italy-Austria 2014-2020 (EUTC / EU funding / Project)
- Total project budget: €288,625.00
Cancer is characterized by uncontrolled cell growth, which can spread to otherwise healthy tissue and organs. Only five to ten percent of cancers are caused by inherited genetics, the majority of the cases are triggered by external factors such as tobacco consumption, diet, infections, or radiation. These external factors may induce so-called epigenetic changes, which may result in cancer cells being no longer recognized by the immune system. Cancer cells thus "hide" from the immune system.
However, some of these epigenetic changes are reversible, and that's where the scientists are going to act on. Utilizing inhibitory compounds (in short, inhibitors) allows prevention of these changes and reactivate previously deactivated genes, so that the immune system can retake action and remove degenerated cells.
The "Epigenetics of Immunity in Cancer" (EPIC) project was started in September 2019, focusing on histone deacetylase (HDAC) inhibitors. The research team comprises of chemists, clinicians, biologists, and bioinformaticians from the universities of Udine, Salzburg, and Trieste, as well as the Institute for Biomedicine at Eurac Research in Bolzano. The team is testing the effect of HDAC inhibitors in cancer cells and their suppressive role in tumor progression. In particular, the University of Udine is checking HDAC inhibition based on a library of HDAC compounds, whereas the University of Trieste is optimizing promising compounds with the aid of computer programs followed by their synthesis. At the University of Salzburg, selected inhibitors are being tested in cell models with respect to their influence on the immune system. Data generated by all partners are shared with bioinformaticians at Eurac Research, who are tasked with their analysis. Invoking next generation sequencing methods, the differences between cancer cells with and without inhibitors are measured: which genes are active, where are they active and what consequences could these compounds have in the human organism. Data obtained from theses analyses are compared to international databases in order to gain additional knowledge on cancer development. In this way, the three-year lasting project is supposed to create the basis for novel advances in cancer immune therapy.
This project is funded by the European Regional Development Fund and the Interreg V-A Italia-Österreich 2014-2020
A pharmacological compound termed "NKL54" changes the epigenetic program in leiomyosarcoma cells: Nucleid Acids Research (NAR) accepted our publication and it went in print yesterday. Want to know more without reading the paper? We happily provide a summary in english and for our German and Italian readers, we have a press release.
EPIC in its final year
Welcome to 2022, the last year of the EPIC project. Far from having in mind to finish soon, we have recently submitted the inhibitor manuscript after a big revision phase once again to the Nucleic Acids Research (NAR) journal (see our blog from 2021-07-26). Further, our collaboration with the immunology group in Salzburg has been refreshed: a mass spectrometer proteomics dataset will be used to investigate the effect of two HDAC inhibitors on the protein production in acute myeloid leukemia (AML) cells.
Thanks for coming to NOI
It was great to see so many interested visitors at our EPIC booth at NOI techpark both on Friday and Saturday. We have talked to many curious students and were asked interesting questions by a broad range of people. Thanks to Emanuela Kerschbamer for taking over the Italian part of our German/Italian presentations! We also have our two animations available for download: move histone-dna.mp4 shows the nucleosome where DNA is wrapped around histone proteins. Movie hdac-saha.mp4 shows an HDAC protein with inhibitor SAHA blocking its catalytic site. Both movies are best viewed in an infinite loop in your favorite movie player.
EPIC at NOI project fair
Curious about the EPIC project? Want to hear more and talk to us?
The yearly EFRE project fair on October 22nd is the perfect opportunity to meet us, we are presenting EPIC at booth 13. See you there.
EPIC project will be prolonged
Today we have received the OK from our Interreg funding agency: we can extend the EPIC project by nine months, the new end will be December 31st, 2022. This is absolutely great news and we are happy to catch up the lost time caused by the shutdowns and slowdowns during the pandemy.
Finally, we have submitted our manuscript where we have compared cellular response to various HDAC inhibitors utilizing RNA-seq, ChIP-seq, and various chemical assays. The work is very comprehensive, by the end focussing on a small inhibitor called NKL54, so we aimed very high and submitted to Nucleic Acids Research (NAR). Fingers crossed!
Third virtual workshop with all partners
Today was our third interregional workshop. Partners from Salzburg and Udine presented their activities, but unfortunately Trieste was absent due to illness. We are wishing a quick recovery and are looking forward to a new date to see what's up in Trieste. Dr. Kerschbamer gave an elaborate presentation summarizing her contributions on the RNA-seq manuscript and two smaller investigations for the immunology group in Salzburg. The great thing here is that the latter was driven by the outcome of the former: insights from the RNA-seq experiments were translated to possible lab work on the immunology side!
Announcing Fall Symposium
We are preparing an online symposium with free participation. It will be held on Oct 5th at 2pm CET. There are going to be a total of five talks. Stay tuned for further information on this blog.
Most people think of scientists working at the lab bench, performing experiments or sitting in front of the computer working on theoretical problems. And this is mostly true. However, science also needs to be administrated. Planning, coordination and reporting to the stakeholder are the tasks that are performed at the (home) office desk. Since EPIC is financed by Interreg V-A Italy-Austria, which is a dedicated regional EU fund, there clearly is a proper interest on our activities from the funding agency's perspective. Is the project progressing as documented in the proposal? Do the different partners cooperate productively? How is the budget spent? Every half a year all partners are thus submitting their progress reports (coordinated by the lead partner in Udine) to their regional funding offices for evaluation. And that's exactly what we are currently doing here at the end of May: we formally demonstrate the progress made in our EPIC project.
Today is a special day: Dr. Kerschbamer joined the EPIC team exactly a year ago.
Online meetings with Udine partner
It's paper writing time. We have already had a series of meetings with the Lead Partner in Udine, who is also the driving force behind the manuscript. We are interpreting gene expression changes of leiomyosarcoma cells in different classes of HDAC inhibitors, which were the basis for the RNA-seq experiments mentioned earlier. We might have some interesting candidate genes, that's something we need to dive into a bit more, though. Overall, it looks like we have an interesting wetlab/bioinformatics paper growing here these days.
Online meeting with Udine partner
Last working day in this year and still fully focused on EPIC with another meeting. Today we had a look at the commonalities in gene expression change between different HDAC inhibitors. It is interesting to see a big expression landscape change already after 6 hours past inhibition. Maybe the commonalities will lead us to some sort of a first simple HDACi signature.
Online meeting with Udine partner
In the beginning of October we have received our first RNA-seq dataset from Udine. A couple of samples were re-sequenced and now it's time to look at it in more detail than we could spend in our virtual workshop. Today we compared two orthogonal approaches to analyzing the sequencing data and agreed on the next steps. Another meeting briefly before Christmas will serve as a follow-up.
Second virtual workshop with all partners
Today we had our second meeting with all network partners. Needless to say, it was online again. We have seen a total of seven presentations in the course of this four hour meeting. It's great to see how the different threads in the project converge to the overall goal of improving HDAC inhibition. Dr. Kerschbamer has summarized our ongoing collaborative work with Salzburg and then went into detail on her RNA-seq analysis, where she has investigated the cellular response to HDAC inhibition looking at a dataset originating from the Udine lab.
Online meeting with Salzburg collaborators
In our monthly get together with our partners from Salzburg, we have identified an interesting experimental setup that can use the transcription factor binding data we have obtained recently and discussed during the meeting.
First dataset has arrived
We have received our first transcriptome dataset from the Udine partner. It contains experiments on several HDAC inhibitors and a time series of RNA production in cells after 6 and 24 hours of treatment.
Online meeting with Salzburg collaborators
Off into the next round of scientific exchange with our lab partners from Salzburg. This time Dr. Kerschbamer has presented her test runs of software that can assign immune cell types from a mixture of RNA-sequenced cells, in this case we have chosen to look at colorectal cancer samples. She further demonstrated how we can use our immune system gene panel on restricting output from differential gene expression data.
Poster has arrived
Even though most of us are in their smart offices at home, from time to time we are visiting our workplace. What a coincidence, today we spent a day at work and our EPIC poster has finally arrived freshly from the press.
Next online meeting with Salzburg collaborators
Our goal is to meet with our network partners in Salzburg on a monthly basis. Today was the follow-up meeting and Dr. Kerschbamer gave a presentation on immune system gene expression in various cancer tissues.
Intensification of collaboration with Salzburg
After last meeting with all partners we have realized that the partners in Salzburg do have a couple of interesting scientific questions which we in Bolzano can help to answer. So today was the first online meeting between Bolzano and Salzburg, fortifying the north-south axis of our network. In this meeting, we have established closer contact and started to understand better what are the details of the questions that the Salzburg groups are currently working on. Dr. Kerschbamer provided an update of the talk she has given two weeks ago during the partner meeting.
First online meeting of all groups
During the last couple of months, science has seen a big change. Many conferences became online events, and we have seen that this type of meeting works pretty well. Sure, we are all missing out the personal contacts that usually are groomed during such events, but scientific content remains excellent.
The same happened in our EPIC network. We have planned a meeting in Trieste in June, but this has been postponed to some later date and we have now held the first online meeting on Cisco's WebEx platform (provided by the Salzburg partners). We got updates on the progress made from each partner and even after 1.5 months, Dr. Kerschbamer from our BZ EPIC team could give a presentation with first analyses of public cancer databases.
Udine has partially opened labs again
After more than two month of lockdown, the labs of our partners are slowly opening. Udine is currently reopening the lab with reduced personnel and working shifts. Others will follow this model.
Welcome Dr. Emanuela Kerschbamer
Our main bioinformatician for data analysis has arrived at Eurac. A very warm welcome to Emanuela Kerschbamer. Dr. Kerschbamer is trained in both the wet lab and in-silico analyses. She has studied biology and functional genomics in Bologna and Trieste, and got her PhD from the Univ. of Padua when working for the Research and Innovation Centre at Edmund Mach Foundation in San Michele all'Adige. Furthermore, she has been visiting scientist in Paris and Boston and after several years of post-doc work at the Univ. of Trento, she joined the EPIC team in May 2020.
SARS-CoV-2 hits EPIC
Lockdown due to the rising pandemic has also hit the EPIC project. Laboratories have been closed, people are starting to work remotely. Lots of experimentalists around the world are becoming concerned that research will stale. Without access to the labs, we will have difficulties in moving forward our experiments. At the moment we can catch up on literature, perform some planning and do administrative work. For us bioinformaticians it is easy to stay home and work from there, but without getting data from the lab, we have to continue tapping external databases and mine them. Let's hope our biologists can return to the lab in not too long time.
Our number crunching server has arrived. It's time to set it up and get some test runs done on it. Let's see how the sequencing pipelines scale on this machine.
First encounter with Bolzano administration
Our local grant administrators in Bolzano have invited all new Interreg project PIs to their office. We have given an overview on cancer and histone acetylases, deacetylases and how inhibition might help improve the immune system attacking cancer cells.
Meet and greet in Udine
Our lead partner in Udine, Claudio Brancolini, has invited all collaborators to join a kickoff meeting. It was good to see all principal investigators (PI) and the students involved in the network. Each PI has briefly presented his/her field of expertise and how they plan to contribute to the project. We have also been informed about important administrative issues.
Looking for a motivated researcher to join the EPIC team
The EPIC project has started at the end of September. Hiring is going on in all labs and we are also looking for a post-doc to join the EPIC team. See our jobs page for the current call.
21 March 2022
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