As a boy growing up in Soviet Russia, Dr. Denis Evseenko was drawn to the wonders of scientific discovery. Though closed off from many of the resources of the Western world at the time, it was a city that housed its own wealth of scientific institutions and provided a fertile and supportive environment for his inquisitive young mind.
Early in his medical training Dr. Evseenko decided to focus entirely on research into embryonic stem cells, specifically the genesis of mesodermal tissues (a broad definition that includes blood, muscle, bone and cartilage). He was excited about the possibilities inherent in cutting-edge science, but also aware of the often complicated path of translational science. He knew if he were to take the next step, he had to do things differently.
“I had a noble vision to develop progressive therapies for the patient,” said Dr. Evseenko. “It was a very practical vision, too, because I realized how limited therapeutic opportunities could be for the basic scientist, and I had seen many great potential discoveries die out before they ever reached the clinic. Could I help to create the bridge between stem cells, research and actual therapeutics?”
From the moment he first arrived at UCLA a little over three years ago, Dr. Evseenko has done just that. He is investigating how regenerative stem cells fundamentally connect, relate and correlate to cancer, and developing new stem cell-based treatments for patients with arthritis as well as ligament and tendon injuries. He has built his laboratory upon the foundational bedrock of cross-collaboration between researchers, clinicians, and the cutting-edge resources unique to UCLA. It is precisely the challenge of taking science “from bench to bedside” that fuels his passion for medicine.
Discovering the Possibilities of Stem Cells
In 2004, Dr. Evseenko left Russia to study at prestigious Liggins Institute at the University of Auckland in New Zealand. It was an exciting time for stem cell research, in which he found his niche. A chance meeting with renowned stem cell scientist Dr. Gay Crooks led to an invitation to join the stem cell research lab that she was developing halfway around the world in Southern California. Though he was newly married and with a young daughter in tow, it was exactly the opportunity the young researcher was looking for.
“California is probably as far away from Russia as you can probably get in terms of weather, but I was always interested in the possibilities there,” laughed Dr. Evseenko. “Gay’s lab was focused on hematopoietic stem cells and it was great because that’s where stem cells originate. We shared a passion for fundamental questions of human development and therapeutics, and how it could be possible to use stem cell science to create new organs and tissues.”
Dr. Evseenko spent five years learning from Dr. Crooks and her colleagues, discovering different ways to control mesodermal cells and creating progressive models to understand their origins and development. His aim was to create improved and more targeted treatments.
Finding His Focus
“Over the years in research, people would often ask me, ‘Is it possible to one day make bones and cartilage from stem cells?’” Dr. Evseenko said. “Because it’s a big problem, particularly cartilage—it degrades as we age and that can become debilitating to our daily lives. It remains one of the major problems in medicine that has no answer.”
Degenerative conditions of the joints and cartilage affect millions of sufferers worldwide. Though rarely life-threatening, these conditions can strike anyone of any age and lead to impairment of activity. As it is a disease with no cure, current drug treatments are focused on pain management and improving quality of life. As the condition worsens, artificial joint replacement is common. It is costly and invasive, and the lifespans of artificial joints are limited (typically around 15 years). With joint replacement costs projected to multiply sevenfold in coming years, it is a looming financial burden for the health care industry.
“When I first arrived at UCLA, I immediately knew I wanted to build the architecture to facilitate the entire cycle here to treat these degenerative conditions,” said Dr. Evseenko. He was invited to become a member of UCLA’s Jonsson Comprehensive Cancer Center and Broad Stem Cell Research Center, and quickly contacted orthopedic surgeons to gauge interest in progressive therapies, and talked with scientists in biomechanics who were leveraging the top-notch robotic facilities at UCLA. “I told them that though we could not do basic science, our lab could help with clinical application of therapies and to create new models and protocols. We could truly build the entire supply line.”
A New Paradigm
Dr. Evseenko’s bold vision of translational science is already blazing new trails in research of regenerative stem cells and their relationship to cancer. Cellular differentiation is the process by which a less specialized cell becomes a more specialized cell type. In cancer, cells can revert to a state that is akin to blast cells (cells that are immature and undifferentiated), resulting in unwanted and uncontrolled cell division. Regenerative stem cells are similar in their ability to reproduce like cancer cells, such as when they reproduce to repair tissue, yet they are subsequently able to “put on the brakes” and not continue to make too many of themselves and mature after reparation is complete. Dr. Evseenko and his colleagues are particularly interested in the mechanisms of rejuvenation that make cancer cells younger and “blast like,” and how these processes are fundamentally related to adult stem cells and the regeneration of specific tissues.
His lab is currently investigating potential correlations between how human cartilage forms in early stages of human fetal development, specifically from five to twelve weeks. “If you look at cells at five weeks, they are like cancer cells in that they have already developed networks to expand and grow, and are dividing like crazy,” said Dr. Evseenko. “Joints that, at five weeks, are two millimeters in size will have grown to one centimeter in size by twelve weeks. A few more weeks after that, they will have tripled in size. This growth is lost post-natal, but in the fetus these mechanisms are highly active.” Dr. Evseenko’s lab is examining these mechanistic links and analyzing the developmental data, applying it to sarcoma and other stem cells in cancers that they can then target for potential future treatments.
As a member of the Broad Center for Stem Cell Research, Dr. Evenseeko is further investigating the potential of human pluripotent stem cells (hPSCs) to be used to grow cartilage. By identifying and characterizing how hPSCs form in early human development, he and his colleagues can overcome the significant obstacles inhibiting their ability to use hPSCs to generate new tissue for transplantation. By working to understand these processes, Dr. Evseenko and colleagues can illuminate the way for potential new treatments including alternatives to joint replacement.
Dr. Evseenko represents the new paradigm of scientists who are translating research and discovery to the clinic to directly impact patient care. He stands at the forefront of the new generation of scientists at UCLA’s Jonsson Comprehensive Cancer Center who are harnessing the regenerative power of stem cells to blaze new trails in medicine and cancer treatment.
Dr. Evseenko’s lab is funded by National Institutes of Health, Department of Defense, California Institute of Regenerative medicine, Arthritis Research National Foundation and UCLA Broad Stem Cell Research Center.
— Peter M. Bracke, 2014