cytocentric visionaries re1

Cytocentric Visionaries: Dr. Robert Elliott

Dr. Robert Elliott, MD PhD, is a Surgeon for Diseases and Cancer of the Breast. He is also Director of the Elliott Breast Cancer Research and Treatment Center in Baton Rouge, Louisiana. He was gracious in joining us for an interview about the recent paper he published in PLoS with colleague Dr. X.P. Jiang, “The adverse effect of gentamicin on cell metabolism in three cultured mammary cell lines: “Are cell culture data skewed?” [1]

Alicia D. Henn
Dr. Elliott, we see you as a Cytocentric Visionary because of your work to find the best culture conditions for mitochondrial health. I read your recent paper about the adverse effect of antibiotics on cell metabolism. How did you come to this project?

Dr. Robert Elliott
About ten years ago, I had looked at EM sections from over 2,000 patients of mine with breast cancer. The patients with normal appearing mitochondria, by number and ultrastructure, had very low grade tumors and did quite well. A second group, with sparse and abnormally shaped mitochondria was an intermediate group. They didn’t fare as well. The third group had hardly any mitochondria and had very aggressive tumors. They hadn’t fared well at all.

People had transferred mitochondria to other types of cells before, but nobody had done it in cancer. So I thought I’d isolate normal mitochondria from a normal cell line, and add them to cancer cells. That reversed their metabolism. I call it MOT, Mitochondria Organelle Transplantation. MOT may be a biotherapy for neurodegenerative diseases and cancer if we can work it out.

Dr. Jiang in our group found that the mitochondria not only are evolutionarily like bacteria, but they still maintain and share similar ribosomes for protein synthesis.

I said, “Well we’ve got to look and see what antibiotics do to mitochondria function.” 

We found out that ciprofloxacin and doxycycline affect the mitochondria and damage these cells badly. It causes membrane potential decrease, increases in ROS, glycolytic enzymes, and glucose transporters. Later on, you get a rebound of ROS and OXPHOS. I think that causes mitochondria DNA damage.

Then I said, “Well, let’s look at all of the papers I’ve been referencing all these years.”

It was good work, don’t get me wrong, but in every one of those papers, even though they’re talking about mitochondrial metabolism and health, they had used antibiotics. So I wrote that paper that you’re talking about.

ADH
So how can we improve cell culture?

RE
We’re totally eliminating antibiotics in our cultures after what we’ve learned. I am convinced, without a shadow of a doubt, that it takes 3 to 4 to 5 generations to get antibiotic defects corrected in the cell. If you wait for a few days without antibiotics before experiments, you still got some damaged mitochondria.

ADH
You think we could apply mitochondrial based therapy to neurodegenerative diseases?

RE
I believe that mitochondria are going to play a big role in cancer and neurodegenerative diseases as well as some of the genetic mitochondria diseases. I truly believe it’s going to be a big biotherapy someday.

ADH
There’s a new concept of metabolism not being just something that runs in the background, but something that can actually drive cell phenotype and cell function.

RE
I totally believe it. I think that genetic research has been great for the last 40 years in a lot of ways but I am truly convinced that if they had listened to Warburg more carefully, that we’d be farther along in treating cancer than we are now.

What cancer does is use aerobic glycolysis most of the time when they’re replicating and growing and metastasizing and they use a lot of iron. If they weren’t able to make ferritin they’d kill themselves off taking iron. They even get rid of the exit protein ferroportin. There’s no tumor that’s homogeneous. There are multiple mutations in same specimen. So why are we trying to treat cancer with all these special mutation targets? Let’s try and attack the common pathways in cancer which are glycolysis and iron metabolism.

ADH
You’ve got me thinking now. We’ve connected microbes with heart valve damage. Should we give heart patients antibiotics if there’s already ROS involved in some mitochondrial damage?

RE
I’m glad you’re thinking the way you’re thinking. My dream is, and I need to live long enough to see it, to have a mitochondria bank for an emergency situation for stroke or heart attack.

ADH
How would a mitochondrial bank work?

RE
Well, it is just a vision. I have thought about it and talked about it a lot. It’ll become a reality when you can learn how to grow them and store them the right way. I do envision that we will be able to isolate mitochondria in a less damaging way. I think that we could have a media that we can put them in to make them healthy, just like we grow bacteria. I believe we’ll be able to do it.
I believe that each hospital might have a mitochondrial bank for emergencies like heart attack and stroke. Neuromedical will have another bank for people who have neurodegenerative disease. It will improve the quality of life. That’s what I believe.
It’s going to take money and its going to take some experts. I guarantee it’s going to take more than me and Dr. Jiang. I really think we need to form a Mitochondria Biotherapy Society. You have to get people that are interested in it to come together, even if it starts with five or six people.

ADH
And we will have to be able to culture mitochondria in vitro?

RE
We’ve actually grown mitochondria. When they are stressed they get into colonies and feed off each other the best they can. We’ve actually grown them for 30-40 days and we took them and froze them and brought them back up. They were weak, they had damage. My goal is to try and see which ones are going to be the best to pull from the human as a donor. I think we can reverse heart attacks, I think we can reverse strokes, and I think it’ll help even Alzheimer’s.

ADH
And changing mitochondrial function may help cancer metabolism as well?

RE
That’s another thing; we found that another thing that was expressed in these cells was that that HIF1 Alpha went up. We saw lot more HIF and that’s very much involved in cancer. In the tumor microenvironment you do have acidic anoxic barriers and they still survive. They are used to living in a very harsh environment.

ADH
Now that we have HIF and a molecular mechanism for why five minutes out of oxygen makes a difference, do you think it’s time to go back and look at cell culture under truly controlled conditions and say “let’s start over with this and see if physiologic oxygen levels do make a difference?”

RE
I think it’s time to do that! I think you have to get a more physiologic media, too. I know it can’t be perfect conditions in vitro all the time but I do think there’s a lot of room for improvement. I think a lot of it is definitely skewed right now.

ADH
Your work with mitochondria is adding a whole new layer to how we handle cells. Is this going to be your legacy?

RE
I hope so. I’m tired of seeing cancer patients suffer. You just couldn’t ignore it. You get involved with doing the research. You see that it may actually be a kind of serendipity in a way I guess you can say. It might be that we wind up kicking neurodegenerative disease, heart disease and stroke, better than any cancer.

ADH
Is there anything else you’d like people to know?

RE
A big step is get antibiotics out of media. If you’ve got a better system that helps keep the cells healthier, you got to know if the mitochondria in the cells are healthy. So I’m trying to get the healthiest cells I can get to have the best mitochondria I can get to isolate and do all these other things.

ADH
We have a concept we call Cytocentric, which means putting the cells first. Incubators and BSCs are certainly not optimal for the needs of the cells; they’re set up for the needs of people. Now you have added another level. We have to be Mitocentric as well as Cytocentric.

RE
That’s exciting to me. I think that’s good!

ADH
Thank you for your time and for your work, Dr. Elliott. We will help get the word out.

 

1. Elliott, R. L.; Jiang, X. P., The adverse effect of gentamicin on cell metabolism in three cultured mammary cell lines: "Are cell culture data skewed?". PloS one 2019, 14 (4), e0214586.

 


alicia author iconAbout the Author

Alicia D Henn, PhD, MBA

Alicia Henn has been the Chief Scientific Officer of BioSpherix, Ltd for two years. Previously, she was a researcher at the Center for Biodefense Immune Modeling in Rochester, NY. Alicia obtained her PhD in molecular pharmacology and cancer therapeutics from Roswell Park Cancer Institute in Buffalo, NY and her MBA from the Simon School at University of Rochester in Rochester, NY.