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Faculty Profile: Alexei Tulin, PhD
Alexei Tulin, Ph.D., is a professor with the SMHS Department of Biomedical Sciences and leader of the department’s epigenetics program. His research has been supported by the NIH, Department of Defense, and other government agencies and foundations. He recently sat down with North Dakota Medicine to talk about his work.
Interview conducted and edited by Brian James Schill
Thank you for your time, Dr. Tulin. We should probably begin with the news of the major research grant you and your team recently received. How would you summarize that award?
This is a three-year award of $900,000 from the Department of Defense through its U.S. Army Medical Research Acquisition Activity program to support our research on prostate cancer. When we were searching for molecules that could inhibit the activity of PARP [Poly-ADP-Ribose-Polymerase] protein, we discovered a large collection of previously unknown “inhibitors” that either kill cancer cells entirely or reverse the cells’ tumorigenic activity—that is, they stop being cancerous. So we’re developing a drug that would target only the tumor cells, but not affect normal cells, in prostate cancer patients. The drug should be effective even against the “castration resistant” prostate cancer, which is the type of cancer that recurs even after the prostate has been removed. Employing these inhibitors for clinical treatments could provide patients with a less toxic, yet highly effective, drug regimen for eliminating remaining or recurring prostate cancer cells.
Dr. Tulin in his research lab in Columbia Hall on the UND campus in Grand Forks
That’s remarkable. And it sounds like what you’re doing falls within the category of Clinical and Translational Science, which the School has made a priority. I assume that if your project is successful you’ll have an opportunity to bring something to market that could help to people suffering from these conditions?
Exactly. Our top priority is to identify effective molecules and conduct all pre-clinical and clinical trials necessary for their approval and implementation to the clinic. This is a long and complex process, requiring interdisciplinary collaborations between several research teams and medical doctors.
So can you help me understand how epigenetics as a discipline fits into this work?
Yes. All cells in our body have the same genes and are programmed to produce the same proteins. Without epigenetic regulation there would be no specialized cells; no brain cells, skin cells, stomach cells, blood cells; all cells in our body would be identical to one another. Epigenetic mechanisms turn appropriate genes on and off during our development and aging. To put this in more technical language, epigenetic research explores the mechanisms that regulate the activation and deactivation of specific genes. Since graduate school, my primary interest has been the organization of DNA “packaging” and studying the normal mechanisms of development. My research team is using the Drosophila melanogaster fruit fly as a model organism, but we were also working with mammalian systems. Using Drosophila we discovered a new player in this regulation game known as the Poly-ADP-Ribose-Polymerase protein, commonly abbreviated as PARP. By itself, PARP has been known for 50 years. Its known functions were limited to its role in DNA repair. The key discovery of my team was showing the connection between PARP and gene regulation. We discovered that PARP can open tightly packaged, inactive DNA by pushing away packaging proteins. This unpacking mechanism is responsible for activating a number of genes involved in development and aging processes. Some of these PARP-regulated genes are known to be linked to cancer progression as well. We found, surprisingly, that PARP-dependent genes include functions that are involved in transforming normal cells into cancer cells. This discovery ignited my interest in cancer.
Do you intend to continue to study cancer specifically at UND? I imagine that if you’re leading an epigenetics team you need to be exploring a little bit of everything.
To be honest, my primary interest is not cancer or disease, but the development of the normal state of organisms. The fundamental biological questions. But we’ve found quite a large collection of new—that is never published—inhibitors in PARP that turn out to be good tools for fighting cancer. We were looking at many types of cancer—breast cancer, kidney cancer, ovarian cancer—but the most progress we saw in inhibiting cancer was in the prostate.
Where were you prior to UND?
Philadelphia. I was an associate professor at Fox Chase Cancer Center, which is part of the Temple University system.
And how long have you been in Grand Forks?
Since July. My kids are still in Philadelphia—the two younger ones. I have a child in college too.
So you’ve not yet experienced a full North Dakota winter…
No, but it does get very cold where I’m from—
Which is where, exactly?
—I grew up in a small satellite city near Moscow. I studied molecular biology and genetics as an undergraduate and eventually earned my PhD in epigenetics at the Moscow State University. I came to the U.S. in 1997 as a postdoctoral fellow at Johns Hopkins University. I like the snow, though. I like skiing. We have a Siberian Huskie named Aike who is very happy here. Unlike in Philadelphia, he can run around outside here.
What brought you to the U.S. originally?
It was becoming very difficult to do science [in Russia] in the 1990s. There are just so many more resources available to do what I do in the United States—more research funding.
Do you miss Russia?
I do. But I think I miss the Russia that I left, not Russia the way it is now. It’s interesting that when I go back it seems that today Russians are more “Americanized” than Americans themselves, you know, the way Americans are portrayed in popular culture and blockbuster movies. There seems to be an inordinate drive towards being successful in business and making fortunes in Russia now. In a way I feel more “foreign” there.