Paul Macklin gave a plenary talk at the 2013 NIH Physical Sciences in Oncology Annual Meeting. After the talk, he gave an interview to the Pauline Davies at the NIH on the need for data standards and model compatibility in computational and mathematical modeling of cancer. Of particular interest:
Pauline Davies: How would you ever get this standardization? Who would be responsible for saying we want it all reported in this particular way?
Paul Macklin: That’s a good question. It’s a bit of the chicken and the egg problem. Who’s going to come and give you data in your standard if you don’t have a standard? How do you plan a standard without any data? And so it’s a bit interesting. I just think someone needs to step forward and show leadership and try to get a small working group together, and at the end of the day, perfect is the enemy of the good. I think you start small and give it a go, and you add more to your standard as you need it. So maybe version one is, let’s say, how quickly the cells divide, how often they do it, how quickly they die, and what their oxygen level is, and maybe their positions. And that can be version one of this standard and a few of us try it out and see what we can do. I think it really comes down to a starting group of people and a simple starting point, and you grow it as you need it.
Read / Listen to the interview: http://physics.cancer.gov/report/2013report/PaulMacklin.aspx (2013)
We just got word from the USC Undergraduate Research Associates Program (URAP) that I will have funding for a 3-person, multidisciplinary team of undergraduates starting summer 2013. This project will aim to assemble a team consisting of a computer programmer, a mathematician, and a biologist to jointly develop and refine user interfaces to make computational modeling of cancer faster and more accessible to a wider group of students. This work goes hand-in-hand with our educational goals in the Consortium for Integrative Comptuational Oncology. More details to come (including a job poster and selection details), but this should be a very fun and worthwhile project.
I’m really grateful to the URAP for this opportunity to fund some bright USC undergraduates in a neat project. Last year, two of our interns (Margy Gunnar and Alice Hyun) were funded under this program, and it was a fantastic experience (at least for me!)
I’m very excited to be featured on this month’s cover of the Notices of the American Mathematical Society. The cover shows a series of images from a multiscale simulation of a tumor growing in the brain, made with John Lowengrub while I was a Ph.D. student at UC Irvine. (See Frieboes et al. 2007, Macklin et al. 2009, and Macklin and Lowengrub 2008.) The “about the cover” write-up (Page 325) gives more detail.
The inside has a short interview on our more current work, particularly 3-D agent-based modeling. You should also read Rick Durrett‘s perspective piece on cancer modeling (Page 304)—it’s a great read! (And yup, Figure 3 is from our patient-calibrated breast cancer modeling in Macklin et al. 2012. 😉 )
The entire March 2013 issue can be accessed for free at the AMS Notices website:
I want to thank Bill Casselman and Rick Durrett for making this possible. I had a lot of fun in the process, and I’m grateful for the opportunity to trade ideas!
Here is my current speaking schedule for 2013. Please join me if you can!
- March 22, 2013: Mathematical Biology Seminar, Department of Mathematics, Duke University, Durham, North Carolina
- Title: From integration of multiscale data to emergent phenomena: the prognosis for patient-calibrated computational oncology [abstract]
- April 19, 2013: Fourth Annual National Cancer Institute Physical Sciences in Oncology Center (NCI PS-OCs) Network Investigators’ Meeting, Phoenix, Arizona
- Title: Exploring possibilities for next-generation computational cancer models that work
together (a conversation starter) [abstract]
- Plenary talk
- May 30, 2013: Mathways into Cancer II International Workshop, Carmona, Spain
- Title: From multiscale data integration to predictions of emergent phenomena: the
prognosis for patient-calibrated computational oncology [abstract]
- Plenary talk
- June 12, 2013: Annual Meeting for the Society of Mathematical Biology (SMB), Mini-Symposium 11: Agent-based simulations in oncology: applications to therapeutics, Tempe, Arizona.
- Title: Progress towards user-friendly, 3-D multiscale agent-based simulators for large (500k+ cells) cancer systems: application to in situ growth and tumor-stroma interactions [abstract]
- June 12, 2013: Annual Meeting for the Society of Mathematical Biology (SMB), Mini-Symposium 26: Patient-Specific Modeling of Cancer, Tempe, Arizona.
- Title: Patient-calibrated 3-D simulations of ductal carcinoma in situ (DCIS) with comedonecrosis and calcification [abstract]
*** UPDATE: Registration has been extended to September 19, 2012, 5:00 pm Pacific Time. ***
The NCI-funded, Physical Sciences in Oncology Center (PSOC) at USC is hosting its second annual symposium on interdisciplinary cancer research on September 27, 2012 from 7 am to 6 pm. The event is free but registration is required.
The symposium will include a great diversity of expertise, spanning cell analysis, cancer evolution, modeling, drug delivery, and therapeutic response. We also have two fascinating keynote speakers: David A. Kirby, author of Lab Coats in Hollywood, and Corby Kummer, senior editor and acclaimed food critic for the Atlantic Monthly. Here’s the confirmed lineup:
Eun Sok Kim (University of Southern California)
Cagri Savran (Purdue University)
Paul Newton (University of Southern California, and Co-Director of CICO)
Paul M. Kulesa (Stowers Institute)
It should be a wonderful event, and I hope you can attend!
You can find the full flyer and description here.
You can find the agenda here.
On May 18th, Paul Newton and I received received significant startup funding from the USC James H. Zumberge Research and Innovation Fund to establish the Consortium for Integrative Computational Oncology (CICO). We’re grateful for this opportunity to build a new resource for USC and the broader cancer community!
CICO seeks to develop and promote cross-disciplinary, integrative collaborations across the USC (particularly the Viterbi School of Engineering and the Keck School of Medicine) in clinically-oriented cancer modeling. Among our guiding principles:
- Computational modeling of cancer must be driven by clinical needs. Modelers need to work hand-in-hand with clinicians at all steps of the modeling process.
- Computational oncology works at its fullest potential when working with clinical data. This focus:
- drives advances in mathematical model design,
- allows us to evaluate and choose between competing models,
- helps biologists to test, validate, and refine current cancer biology orthodoxy,
- helps clinicians to better interpret their data, and
- is most likely to lead to computational tools that will make an impact in the clinic.
- Integrative computational oncology holds the potential to integrate advances from mathematical modeling, experiments, and clinical data into comprehensive tools that give a better understanding of cancer than any of these individual pieces alone.
- Integrative computational oncology must include student education at its core, to create a true “ecosystem” of clinically-focused modeling students from the undergraduate to postdoctoral level.
You’ll be hearing a lot more about CICO as we ramp up in the coming year!
Today, Paul Newton and I submitted a joint grant to the National Science Foundation in the Physical and Engineering Sciences in Oncology (PESO) program. PESO is a neat program jointly run by the NSF and NCI, that has spun off the NCI’s recent physical sciences approach to cancer. Our proposal brings together a a variety of techniques (spanning agent-based models, signaling, tissue biomechanics, fluid flow, nonlinear transport, and Markov chains) to study targeted aspects of cancer metastasis, from early microinvasion to circulating tumor cells (CTCs) to whole-body dissemination of metastatic disease.
On a personal note, this is my first proposal as a Co-PI. *fingers crossed*
For those of you in the neighborhood, I’ll be giving a on patient-calibrated computational modeling of breast cancer, and on the role of mathematical modeling in facilitating a deeper understanding of pathology and mammography.
Monday, February 6, Center for the Applied Mathematical Sciences (CAMS) at the University of Southern California.
Link and abstract: http://cams.usc.edu/Colloquia/2-6-2012.html
I am pleased to report that our paper has now been accepted. You can download the accepted preprint here. We also have a lot of supplementary material, including simulation movies, simulation datasets (for 0, 15, 30, adn 45 days of growth), and open source C++ code for postprocessing and visualization.
I discussed the results in detail here, but here’s the short version:
- We use a mechanistic, agent-based model of individual cancer cells growing in a duct. Cells are moved by adhesive and repulsive forces exchanged with other cells and the basement membrane. Cell phenotype is controlled by stochastic processes.
- We constrained all parameter expected to be relatively independent of patients by a careful analysis of the experimental biological and clinical literature.
- We developed the very first patient-specific calibration method, using clinically-accessible pathology. This is a key point in future patient-tailored predictions and surgical/therapeutic planning.
- The model made numerous quantitative predictions, such as:
- The tumor grows at a constant rate, between 7 to 10 mm/year. This is right in the middle of the range reported in the clinic.
- The tumor’s size in mammgraphy is linearly correlated with the post-surgical pathology size. When we linearly extrapolate our correlation across two orders of magnitude, it goes right through the middle of a cluster of 87 clinical data points.
- The tumor necrotic core has an age structuring: with oldest, calcified material in the center, and newest, most intact necrotic cells at the outer edge.
- The appearance of a “typical” DCIS duct cross-section varies with distance from the leading edge; all types of cross-sections predicted by our model are observed in patient pathology.
- The model also gave new insight on the underlying biology of breast cancer, such as:
- The split between the viable rim and necrotic core (observed almost universally in pathology) is not just an artifact, but an actual biomechanical effect from fast necrotic cell lysis.
- The constant rate of tumor growth arises from the biomechanical stress relief provided by lysing necrotic cells. This points to the critical role of intracellular and intra-tumoral water transport in determining the qualitative and quantitative behavior of tumors.
- Pyknosis (nuclear degradation in necrotic cells), must occur at a time scale between that of cell lysis (on the order of hours) and cell calcification (on the order of weeks).
- The current model cannot explain the full spectrum of calcification types; other biophysics, such as degradation over a long, 1-2 month time scale, must be at play.