After going through the IACM PDF file of workshop attendee details, I'm tagging the following people @lmheiser, @Gaodch, and @jiyang.yu to start a conversation about our shared interests in understanding how context (microenvironment, cell-cell interaction, or cell state context) alters response to drugs (also opening up the discussion to anyone else as well of course).
For example, my specific question is when does context create a drug-response that results in increased aggressiveness? I would love to schedule an interactive discussion.
Created by Kristen Naegle knaegle @knaegle good ;-) Looks like 5/24 3pm EST was a majority, so I signed up including @lmheiser and @jiyang.yu
@Gaodch does that work for you or @liudon or @aedinc. Sign up if it does!
5/23, 4pm EST works for me. Don Liu Thanks @lmheiser. The following works for me:
5/22, 1pm EST (sorry @knaegle, cannot make it 2pm EST)
5/23, 4pm EST
5/24, 3pm EST
@lmheiser. These work for me, with a preference on 5/22 since it's in the beginning of the week.
5/22, 2pm EST
5/24, 3pm EST Kristen and I met this morning, and are still fleshing out ideas for a project. We are trying to get something scheduled for early next week so that we can start to solidify and move forward in advance of the workshop.
@Gaodch, @jiyang.yu: it would be great to have you participate in these discussions. @aedinc, please also feel free to join in.
Here are some possible times:
5/22, 1pm EST
5/22, 2pm EST
5/23, 4pm EST
5/24, 12pm EST
5/24, 3pm EST
Best,
Laura Hi @aedinc! Here is a link that describes our MEMA platform: www.synapse.org/MEP_LINCS .. you won't have to go far ;)
We have been using this platform to understand how signals from the microenvironment influence cancer-associated phenotypes, such as proliferation, differentiation, and therapeutic response. Your idea to predict site of metastasis is an interesting one, and I'd be interested in chatting about this more.
Best,
Laura @lmheiser, I am interested to learn more about your microenvironment microarray platform. Have you published on this? I would like to explore if a primary tumor has dependence (on certain growth factors/cytokines etc) and if these can predict site of metastasis. GTeX normal tissue gene expression data show highly variant tissue specific profiles of these. For example bone is very different to liver etc. @liudon To test this we would need to profile a large number of cell lines or primary lines, that have known profiles of metastatsis (eg to bone v lung v liver v brain etc). Aedin
Sorry, @lmheiser, cannot make it 12pm now, crazy Friday. Will catch up later. Thanks. Yes, I can. Luckily a meeting was moved since I first replied. I'll go sign up now for 12pm EST. I am available 12pm EST friday. @knaegle, @Gaodch: can you make it then?
Sorry, have an important meeting Friday 1pm EST, but 12pm EST is good to me if possible. Thanks. @lmheiser I've reserved Friday 1pm time slot to discuss. @Gaodch, @jiyang.yu and others, please feel free to join.
I have super-resolution microscopy to study the synapse between immune cells and tumor cells/
We also have strong expertise and experience to study the immunological synapse between immune cell and tumor cells.
Can we put all the technologies and expertise together to understand the tumor microenvironment and synapse during metastasis?
Thanks
Don Thanks @lmheiser for coordinating! Friday 1pm works for me! Last week we had some interesting discussions about topics in this thread, including various technologies we could use to tackle the problem. Here are some possible times to meet again:
Thursday 1pm EST
Friday 12pm EST
Friday 1pm EST Can't make it today with traveling, sorry all - Apologies everyone, I'll have to skip today's call, I'm under the weather. I look forward to reading the notes!
Absolutely @aedinc, these calls are open to everyone. In fact, it's encouraged to join as many calls during the formulation stage as you wish. (If you see the notes connected to Week 1 calls, Nas covers that very topic).
Hi
This is interesting to me. Can I join the 5/12 call? signed up 5/12 4pm EST as well. Thanks Laura. 5/12 at 4pm works for me. Thanks for organizing Laura.
Looks like the 5/11 1pm slot may already be taken. How about 5/12 at 4pm EST? 5/11 1 pm
We had a great first discussion yesterday, and I look forward to continuing them on with this group. Here are some possible times for us to meet next week:
5/8 1pm EST
5/10 3pm EST
5/11 1pm EST
Please let me know what might work for you, and then I will reserve a teleconf time. @knaegle Thanks for tagging me. Really sorry for not being able to attend any proposed time this week for this discussion.
Our internal single-cell RNA-Seq data of stroma (microenvironment) and tumor cells from a chemo-resistant PDX model suggested some interesting findings on subpopulations in both stroma and tumor cells that might contribute to drug resistance. I have privileged access the single-cell RNA-Seq (both C1 and drop-seq) facility in my department (dedicated to three comp bio faculty only). Also my group has been developing network inference algorithms from scRNASeq data taking advantage of my rich experience in bulk-tumor based network reverse engineering. The scRNA-Seq technology and systems biology algorithms will definitely be able to help to address questions like this. Thursday 12pm works for me. Unfortunately I can't do 12:00 on 5/4 Great @lmheiser, I signed us both up at 12pm 5/4. @soloriol @Gaodch, please join us!
Hi all,
We have generated a microenvironment microarray platform that allows us to interrogate the effects of 1000's of combinatorial microenvironmental proteins (ECMs and ligands). Using this platform, we can assess the influence of microenvironmental signals on cell phenotype, including drug response. I'd be happy to discuss further in a teleconference this week.
I'm available 5/4 12PM EST I have a 3D printing platform that I am currently using to evaluate how fibroblasts effect breast cancer metastasis. We have some early data that indicate we can drive a very epithelial-like breast cancer cell line through EMT when fibroblasts are in direct contact with the cancer cells. We can essentially create different tissue layers and evaluate the patio-temporal effect on cancer cells. I don't know if that would be a useful tool for what you were thinking, but I would like to discuss in more detail. The interactions between immune cells and the tumor microenvironment include:
1) soluble factor production (transforming growth factor-beta, indoleamine 2,3-dioxygenase, interleukin [IL]-4, prostaglandin E2) by tumor cells or other cells in the tumor microenvironment;
2) inhibitory cells at the tumor site, which include myeloid-derived suppressor cells, regulatory T cells, tumor-associated macrophages, tumor-associated fibroblasts, and tumor cells (Pietra et al., 2016);
3) dysfunctional immune cells at the tumor site. These dysfunctional immune cells are characterized by the upregulated expression of several inhibitory receptors, such as PD-1, and the downregulation of critical, stimulatory NK receptors, such as NKG2D.
4) Among these factors, one of the most important cellular interactions in the tumor microenvironment is the interaction between immune cells and tumor cells, also known as the immune cell immunological synapse or immune synapse (IS). A immune cell must form an effective IS with susceptible target cells to kill them.
I am looking for a collaborator who is interested in the immune synapse in the tumor microenvironment. We have been working on immune cell synapse for more than 20 years.
I have an NIH Grant deadline May10 and will be limited in my ability to discuss until May11. @lmheiser, @snyderjc1 and @Gaodch
How about one of the following:
5/3 3PM EST
5/4 11AM EST
5/4 12PM EST
Hi @knaegle, @snyderjc1, and @gaodch,
Thanks for coming up with a new topic, this is a idea that could move the field forward. To move it along further I suggest signing up for a teleconference this week. The signup sheet can be found [online](https://docs.google.com/spreadsheets/d/1hY53jRaqoBMnb9HhuE8dN3k4ejX37gG-4C4pattxkuM/edit#gid=1701101959) and as many of you can sign up for as many topics as you'd like. Just put the 'call topic' in column F. The workshop organizing committee is ready to host and facilitate these calls as need be, all you need to to do is call in the number in the column A. You can use this forum or communicate offline to find a time when all of you can call in to discuss further.
Perhaps @lmheiser will also be interested in joining?
The sooner you circle around a project the more time you will have to prepare for a successful project in June. Please feel free to ask me if you have any questions about the process.
-sara I am very interested in the topic of chemoresistance. Thank Kristen for starting this discussion. Development of chemoresistance remains the major therapeutic barrier in the treatment of metastatic cancer. This makes me believe that to study drug response and mechanisms of chemoresistance have great clinic relevance. We may address the question from both microenvironment and tumor cell themselves.
I have an EMT lineage tracing model, established by using multiple transgenic mouse model (MMTV-PyMT/Fsp1-Cre/Rosa26-GRFP, Tri-PyMT). We have shown that EMT tumor cells exhibit survival advantages under chemotherapeutic stress and significantly contributed to the formation of chemoresistant lung metastasis. These have encouraged me to further investigate EMT-targeting strategies as a means to overcome chemoresistance in breast cancer.
We are using our Cancer rainbow technology (as discussed in my post regarding "only the strong survive") to grow organoids (intestinal and mammary). Therefore, we can compete multiple genetic drivers with one another and then test current oncological treatments. Also, we have a collaborative P30 Screening center with access to >300K small molecules for drug screening.
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