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Patient-Centered Innovation

New neurosurgery chair combats brain cancer with multifaceted biological approach

As a boy in the small mountain city of Zakopane, Poland, Maciej S. Lesniak, MD, MHCM, never imagined he would become a physician because he saw that his mother, an obstetrician and gynecologist, was often rushing off at all hours to deliver babies. With a zeal for languages and culture, stoked by his family’s eventual moves to Munich, Germany, and then to Chicago when he was a teenager, he thought he’d pursue a career in international law. But as an undergraduate at Harvard University, he came to realize that legal “paperwork” appealed to him much less than the science and human interaction of medicine.

Today, as a world-renowned neurosurgeon and brain cancer researcher, Dr. Lesniak embraces the long hours of his profession because he loves what he does.

“I can’t imagine doing anything else in life,” says the new chair of the Department of Neurological Surgery at the Feinberg School of Medicine, who investigates biological approaches to attacking malignant brain tumors and works to translate that research into clinical therapies for his patients.

Lesniak developed his passion for neurosurgical oncology while a student at the Johns Hopkins University School of Medicine. Nudged by his mentor, Catherine D. DeAngelis, MD, MPH, the fourth-year student served a month-long neurosurgical rotation under two Hopkins professors involved in cutting-edge research: then-neurosurgery chair Donlin M. Long, MD, PhD, and current chair Henry Brem, MD.

Maciej S. Lesniak, MD, MHCM

Maciej S. Lesniak, MD, MHCM

“I fell in love with the profession, mostly because of the people; I was fascinated by what they did,” says Dr. Lesniak, noting that Dr. Brem had been leading clinical trials on the breakthrough drug Gliadel, approved by the U.S. Food and Drug Administration in 1996 for treating patients with recurring gliomas. “I thought, ‘Here is a field where you can focus on a certain disease, you can actually do research, and you can run clinical trials and do something amazing.’”

He stayed at Hopkins to complete in 2002 both a six-year neurosurgery residency and a two-year fellowship in neurosurgical oncology and immunology. Since then, Lesniak has become a leading researcher of glioblastoma multiforme, the most aggressive primary brain cancer. Acclaimed also for his surgical skills and patient care, he has received multiple accolades, including repeated listings in Castle Connolly’s “America’s Top Doctors,” and this year, the National Institutes of Health “Outstanding Investigator Award.”

Currently the principal investigator or co-investigator of eight NIH-funded studies, totaling more than $25 million in grant support, Lesniak comes to Northwestern after 12 years at the University of Chicago, where he was a tenured professor of neurosurgery and neurology and the director of the Neuro-Oncology Research Laboratories. At Northwestern, Dr. Lesniak is also a member of the the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, and is the Lurie Cancer Center’s program leader for Neuro-Oncology.

With more than 175 peer-reviewed journal articles and book chapters, he collaborates with and mentors other oncological researchers in the fight against primary and metastatic brain cancer.

“I am absolutely thrilled to be here,” says Lesniak, Michael J. Marchese Professor at Feinberg. “I think Northwestern is the vision of the future of medicine in this country. The amount of effort that is being dedicated to invest in people and the delivery of care and the science is unprecedented. This is one of the reasons I wanted to be a part of it.”

Bench to Bedside

Lesniak describes his research as broad because it encompasses four domains: stem cell biology, nanotechnology, gene therapy and immunotherapy. “In my opinion, those are four major areas where a lot of the biologically-based discoveries will be made,” he says. “This doesn’t negate the importance of chemotherapy or radiation therapy. But my interest has been in these biologically-driven agents and developing them with the FDA for use in clinical trials.”

Fascinated by immunotherapy since his residency at Hopkins, Dr. Lesniak has been investigating what makes brain tumors immunosuppressant and why the immune system is weak in the context of brain cancer. Several years ago, he and his colleagues, as well as other research teams around the country, identified that the over-accumulation of tumor-infiltrating regulatory T cells (Tregs), especially thymus-derived natural Tregs, plays a key role in immunotherapeutic failure in patients who have glioblastoma multiforme.

A postdoctoral fellow mentored by Dr. Lesniak at the University of Chicago, Derek A. Wainwright, PhD, who is now an assistant professor, conducted research indicating that a tryptophan-catabolizing enzyme overexpressed in glioblastoma multiforme influences Tregs levels in malignant tumors.

Brain tumor. Colored scanning electron micrograph (SEM) of a glioma, a type of tumor that arises from glial cells of the central nervous system. STEVE GSCHMEISSNER/SCIENCE PHOTO LIBRARY

Brain tumor. Colored scanning electron micrograph (SEM) of a glioma, a type of tumor that arises from glial cells of the central nervous system.
STEVE GSCHMEISSNER/SCIENCE PHOTO LIBRARY

“Once we identified this pathway and published our findings, we then worked with a pharmaceutical company that has an agent that inhibits this pathway to start a Phase I clinical trial,” Dr. Lesniak explains.

In the realm of stem cell biology, he points to work he has done over the past five years in conjunction with Karen Aboody, MD, who co-leads the developmental cancer therapeutics program at City of Hope in California. In this venture sponsored by the National Institute of Neurological Disorders and Stroke, Drs. Lesniak and Aboody have been developing a neural stem cell-based therapy for delivering an oncolytic virus to brain tumors.

“Karen and I have championed this to the FDA at numerous levels,” says Dr. Lesniak, noting that he is about to finalize the investigational new drug (IND) application. “I think we’re going to have a trial in a year or two.”

The nanotechnology segment of his research remains in earlier stages. Initially working with scientists at Argonne National Laboratory, Lesniak and his team developed a way to target malignant cells using inorganic titanium dioxide nanoparticles, a photoreactive material that can bond with biomolecules. Linked to an antibody, these nanoparticles bind specifically to cancer cells and will interfere with their mitochondria, potentially destroying them when exposed to focused visible light.

“We’re working on this line of research now with a group from the University of Cambridge — in terms of both optimizing the nanoparticles and building a machine that can actually deliver the magnetic field,” Dr. Lesniak says.

In addition to research and other facets of his career – teaching, writing and now, increasingly, administration – Lesniak maintains a robust neurosurgical practice. Approximately 70 percent of his practice involves intracranial surgery to remove both benign and malignant tumors, including skull-based and pituitary tumors. He has performed many awake craniotomies when tumors reside close to critical functional locations in the brain.

Compassionate, Personalized Care

With a warm and personable demeanor, Dr. Lesniak consistently earns high marks on physician-rating websites for his bedside manner and willingness to spend time with patients, as well as his diagnostic and surgical skills, promptness and follow-up care.

“When people call with a diagnosis of a brain tumor, it is one of the scariest moments in their lives… My philosophy has always been that we are here to make this experience as easy as possible on them,” he says. Unless in the operating room all day or away from Chicago, “I see people on their schedule, not mine.”

Another key aspect of his care approach is that he educates patients about their condition and provides options. “Many patients I see with malignant brain cancer,” notes Dr. Lesniak, “come to me simply because they’ve not been given any hope or options.”

Dr. Lesniak and Milo enjoy fall in Chicago.

Dr. Lesniak and Milo enjoy fall in Chicago.

For patients diagnosed with malignant brain cancer, the standard of care is tumor resection, followed by chemotherapy with temozolomide and radiation therapy. “If you look at the two-year survival of patients who are on these therapies, it’s about 25 percent,” says Dr. Lesniak. “But without them, the survival rate drops to single digits.” He hopes the biological therapies he is working to develop will significantly improve the prognosis for such patients.

Whatever the diagnosis, prognosis or intervention, Dr. Lesniak remains deeply connected to his patients throughout the course of their treatment and beyond. “I’m very involved in the lives of my patients throughout the entire process,” he says. “It’s not about what I do in the OR; it’s about what I do outside of the OR. I want to be a resource to everyone involved in coordinating a patient’s care.”

At the University of Chicago, after clearing multiple hurdles, Dr. Lesniak even started an innovative, new pet therapy program: oncology patients could bring their own dogs to the hospital.

“I’ve had many patients who’ve been more concerned about being in a hospital for too long because they didn’t know what was happening to their dog or cat,” he explains. “That was quite striking. If we are really taking care of people and their needs, and their needs include maintaining bonds, why should pets be treated differently? We need to recognize that they are an important part of providing care.”

A lifelong dog lover himself, Lesniak lives with a Portuguese water dog named Milo. His four-legged friend accompanied him to campus at the University of Chicago, initially to participate in a colleague’s research project on canine interaction and patient stress levels.

Promoting Positive Morale

As head of neurosurgery at Northwestern, Dr. Lesniak, who is 45 and radiates youthful energy, says his priority is to create a positive work atmosphere that focuses on patients and their needs.

“We spend most of our day at work – 10, 12 and sometimes 16 hours,” he observes. “By the time you get home, you may have only a couple of hours to spend with your loved ones before going to sleep.

“So it is very important for us to have a healthy working environment — collegial, enthusiastic, supportive, productive — which translates into happy people at home, who come back to work and actually want to be here. When we do that, we take that positive attitude to our patients.”