Chapter 07: Sarcoma Studies
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Description
In this Chapter Dr. Pollock talks about his shift in research focus to the molecular biology of sarcomas, discussing along the way two significant programs built as a result of his work.
He begins by talking about his 8-9 year collaboration with Dr. Dihua Yu, which began as a sarcoma-oriented laboratory, but eventually evolved to be a more encompassing initiative. In 2006, Dr. Pollock explains, he approached John Mendelsohn with the idea of creating a Sarcoma Research Center Program, as those studying the diseased were dispersed over the entire institution. The Program was created so researchers could share researchers and trainees. Dr. Pollock then explains that his study of sarcoma tumors initially looked at the role of the tumor suppressor gene p53, commonly mutated in this disease. He learned that p53 controls or influences many processes, including the regulation of angiogenesis. He explains how p53 regulates angiogenesis. He also sketches a few discoveries: angiogenesis can be reversed by restoring normal p53 genes to the tumor, a therapy that also restores cell cycle regulation and diminishes the invasiveness of the sarcoma. He notes that these studies did not go into clinical trials because of his increasing administrative responsibilities.
Identifier
PollokRE_02_20121010-C07
Publication Date
10-10-2012
Publisher
The Making Cancer History® Voices Oral History Collection, The University of Texas MD Anderson Cancer Center
City
Houston, Texas
Interview Session
Raphael Pollock, MD, Oral History Interview, October 10, 2012
Topics Covered
The Interview Subject's Story - The ResearcherThe Researcher Professional Practice The Professional at Work Collaborations Overview Definitions, Explanations, Translations Understanding Cancer, the History of Science, Cancer Research Discovery and Success Multi-disciplinary Approaches Building/Transforming the Institution MD Anderson Impact
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.
Disciplines
History of Science, Technology, and Medicine | Oncology | Oral History
Transcript
Tacey Ann Rosolowski, PhD:
Let me just quickly say that this is Tacey A. Rosolowski, and we’re about to begin our second session interviewing Dr. Raphael Pollock, Surgical Oncology, and the time is 2:50, and it is October 10, 2012. So you were saying when you set up your research lab—
Raphael Pollock, MD:
I was— Well, when we were making the transition from immunology to molecular biology, I was very fortunate to be able to recruit Dr. Dihua Yu, who is a senior faculty member at Anderson now. She and I partnered initially in establishing a sarcoma research laboratory that was a component of a space. Dr. Yu’s interests were, and remain focused on, breast cancer, but we had the opportunity to work together in developing what at the time was a smaller sarcoma-oriented research laboratory component within this very much larger laboratory that was in space that belonged to the Department of Surgical Oncology.
Tacey Ann Rosolowski, PhD:
Now, was defining that laboratory kind of a bureaucratic thing or were there actual equipment and—?
Raphael Pollock, MD:
It was a regular laboratory. Part of the problem is that we didn’t have enough separate rooms to be able to give each investigator their own laboratory with their name on the door, no one else’s. Philosophically I thought that it would be better, in any event, to try to encourage users to share resources. There’d be economy of scale and potentially crosspollination between investigators and trainees. I wanted to make it as egalitarian a scenario as possible. So that was the context in which this laboratory program was initially established. So Dr. Yu and I worked together for eight or nine years, and ultimately she decided that her career interests would be better served by being a full-time investigator in a full-time laboratory research department. Luckily she was able to be retained by the institution, so she went back into Mien-Chie Hung’s department, where she remains to this day as one of the senior leaders. What happened as part of that transition is part of my own personal story, as it were. The woman who I ultimately married, having finished her research training, was interested in an opportunity in sarcoma research, and so we decided to pool resources, and she moved into the role of principle investigator in the laboratory.
Tacey Ann Rosolowski, PhD:
And her name is?
Raphael Pollock, MD:
Dina Lev. And so my wife and I have shared this research enterprise, if you will, now for about almost a decade.
Tacey Ann Rosolowski, PhD:
Really? Now, that is the Sarcoma Research Center Program?
Raphael Pollock, MD:
Correct.
Tacey Ann Rosolowski, PhD:
And so that’s endured for quite a while.
Raphael Pollock, MD:
Yes, it has.
Tacey Ann Rosolowski, PhD:
And so tell me—I mean—when you started that program, did you have in mind that it was a program, or did it start as a laboratory and then the idea of having a program grew?
Raphael Pollock, MD:
Well, it started as a laboratory, and it grew to be even more encompassing. In 2006, as part of a retention opportunity here at Anderson, I approached John Mendelsohn about the possibility of setting up a multidisciplinary sarcoma research laboratory/center. The vision was driven by the reality that sarcoma laboratory research at MD Anderson was very fractionated and there were a number of investigators in multiple departments who were in separate, disconnected, noncontiguous space, and so the interaction was modes, to say the least. So the idea was to have a dedicated piece of real estate that could house everyone under one roof and then amplify this philosophy of shared resources, shared trainees, shared research conferences. So that’s what we were able to create.
Tacey Ann Rosolowski, PhD:
And where is that located?
Raphael Pollock, MD:
It’s currently located in SCRB 4 [South Campus Research Building 4], but the space that we were given initially to start this was in the old Naomi Street Building, so right by the Astrodome.
Tacey Ann Rosolowski, PhD:
So tell me about the evolution of your research when you were focused there and now the research that you’re undertaking with Dr. Lev, and have undertaken.
Raphael Pollock, MD:
So, initially we were very interested in looking at a molecule called p53, which is a tumor suppressor gene, and it happens to be the most commonly mutated gene in soft tissue sarcoma, so we wanted to learn more about what it’s role was in sarcoma and whether, if mutated, it might be the target of therapeutic intervention such as gene restorative therapy. So this was work that I did in collaboration with Dr. Yu in the early period of transition, and it was very fruitful investigations. We learned, among other things, that p53 controlled many, many biological processes, or at least influenced many biological processes in soft tissue sarcoma including the regulation—or partial regulation—of angiogenesis. So that was, at the time, an interesting and novel observation, since replicated by many people in many tumor systems.
Tacey Ann Rosolowski, PhD:
Can you tell me how it regulates angiogenesis?
Raphael Pollock, MD:
Well, it regulates it in two different ways. There is a growth factor called vascular endothelial growth factor—VEGF—whose elaboration is apparently, in sarcoma, under the control, or at least partial control, of p53 such that if p53 as a suppressor gene is mutated, then the regulation of this angiogenesis stimulating factor is disrupted and sarcoma cells can produce this in super-abundant amounts. The factor alone is not enough to trigger growth, however, and it needs a specific cell surface receptor. This is likewise under the control of p53 such that if p53 is mutated, the suppressor function is lost regarding the receptor, and so receptor expression likewise increases, so the cells are able to both secrete more of this factor as well as elaborate more of the receptor. So it stimulates the growth of angiogenesis.
Tacey Ann Rosolowski, PhD:
So the same mutation controls both of those functions?
Raphael Pollock, MD:
Well, I can’t tell you if the same mutation specifically controls both, but mutations in this gene. There are many, many mutations in the gene, and we hardly scratched the surface in terms of characterizing all of the different mutations, choosing instead to try to focus on a couple that might be targets of therapeutic intervention.
Tacey Ann Rosolowski, PhD:
How would your discovery about these two processes—? How would they lend themselves to therapeutic intervention?
Raphael Pollock, MD:
Well, by restoring normal wild-type p53 genes in sarcomas in which the gene was mutated, it changed a number of critical growth processes. It decreased angiogenesis remarkably. It restored certain types of cell-cycle regulation. It decreased invasiveness and migratory abilities of the sarcoma cells. So it really had a very profound impact in multiple different directions.
Tacey Ann Rosolowski, PhD:
Wow. Interesting. So you took normal, or unmutated, p53 and went into the sarcoma?
Raphael Pollock, MD:
We were able to reintroduce it in an approach that was analogous to gene therapy type approaches, and that was work, as I said, that I did in collaboration with Dr. Yu.
Tacey Ann Rosolowski, PhD:
What happened to that research?
Raphael Pollock, MD:
It got published, and it became the basis of several R01 grants from the NIH. And we never matured it to the point that it might go into clinical trials simply because I became more and more busy with administrative responsibilities, and when the transition to creating the Sarcoma Research Center was made, there were other projects that became even more interesting to Dr. Lev and myself.
Tacey Ann Rosolowski, PhD:
Do you want to tell me about those now?
Recommended Citation
Pollock, Raphael E. MD and Rosolowski, Tacey A. PhD, "Chapter 07: Sarcoma Studies" (2012). Interview Chapters. 1319.
https://openworks.mdanderson.org/mchv_interviewchapters/1319
Conditions Governing Access
Open
