Talking translational research with Dr. Deepa Kolaseri and Dr. Manish Patel
Curious about how scientific discoveries become real-world therapies? Physician-scientist Manish Patel, DO, and Deepa Kolaseri, PhD, scientific director of translation chat about the journey of translational research from laboratory to patient care highlighting its importance and impact on healthcare advancements. Drs. Patel and Kolaseri are our special expert guests at our next Fireside Chat, happening August 13!
What is your educational background? What intrigued you about your field of specialty, and what brought you to the University of Minnesota?
Dr. Deepa Kolaseri: I have a PhD in Immunology from the University of Alberta, Edmonton, Canada. During my doctoral studies, I studied how a healthy immune system fights off viral infections. Later, as a postdoctoral scientist, I researched how the immune system reacts to cancer. This led me to develop a new therapy for neuroblastoma, a type of cancer in children, based on certain proteins found in cancer cells. I was able to turn my research into real treatments for kids with this cancer. The University of Minnesota provided an opportunity to leverage my experience to enhance the translation of research from laboratory into clinical applications.
Dr. Manish Patel: I went to undergraduate at Vanderbilt University and majored in molecular biology. I attended Medical school at Kirksville College of Osteopathic Medicine, and did my Residency at Northwestern University’s Evanston Campus. I spent one year as an Empire State Research fellow at Winthrop University Hospital, and completed a hematology/oncology fellowship at the University of Minnesota. I have been interested in oncology since my fourth year of medical school when I did a rotation at IU Medical Center. My first rotation in residency was oncology; I remember two particular patients that got me hooked after my oncology rotation. The first was a patient with a gastrointestinal stromal tumor or GIST—a type of cancer that begins in the digestive system—who had an amazing response to Gleevec, an oral targeted therapy medication used to treat cancer which, at that time, was typically only used for a type of leukemia. The second patient was a man with lung cancer who had a near complete response to gefitinib, a type of targeted cancer drug that tells cancer cells to stop growing. A few months later, gefitinib was withdrawn from the market as "ineffective" and I learned later why that was the case. I came to Minnesota as I was following my wife who matched into the UMN Neurology program. When I moved here, I started to volunteer in Dr. Robert Kratzke's lab.
What is translational research and who does it impact?
Dr. Kolaseri: Translational research is the process of taking discoveries made in a laboratory and turning them into practical applications to improve patient outcomes and enhance public health. It could be new treatments, therapies, diagnostics or preventative measures that could be used in a clinical setting. Translational research impacts patients and their families, healthcare providers, research scientists, policymakers, and biotechnology and pharmacology companies who help create therapies and medicines for patients.
Dr. Patel: Translational research, to me, means research that bridges the gap between laboratory research and clinical research. This, of course, should have an impact on patient care as its goal in the end is to improve outcomes for patients. When done well it should be bi-directional. That means we learn something about biology from clinical experience that goes back to the “bench,” back to lab studies, to gain new information based on the findings.
Why is translational research so important? What stages of cancer research does your work affect?
Dr. Kolaseri: Translational research is very important because it transforms scientific discoveries into practical medical applications that improve patient care and public health. It bridges the gap between laboratory research and clinical practice or public policy, and therefore accelerates the development of new treatments, therapies, and diagnostic tools.
My work primarily focuses on treatment, specifically immunotherapy, for a variety of cancers. We are currently working to expand our support to include other areas such as diagnosis, prevention, and beyond.
Dr. Patel: Translational research is critical. We can only do so much with clinical trials—we cannot answer all questions with them. By the time something gets to trial, we can see the final outcome, but we don't always understand why. Samples collected during research go back to the lab to start to understand why. My lab team studies new therapies for cancer and tries to develop strategies to take that work to the clinic. My clinical work involves many phase I and phase II trials, which are the first tests of the drugs, or combinations in trials where we try to learn how best to use these drugs for patients.
What are some examples of translational research related to cancer?
Dr. Kolaseri: 1. Development of Targeted Therapies: HER2-Positive Breast Cancer: Research identified the HER2 protein as a driver in certain breast cancers. This led to the development of drugs that specifically target HER2-positive breast cancer cells. These treatments were then applied to other cancer types that also expressed, or carried, the HER2 protein.
2. Immunotherapy: CAR-T Cell Therapy: Engineering of patients' T-cells to express chimeric antigen receptors (CARs) that target cancer cells. T-cells are a type of white blood cell that help protect the body from infection and can help fight cancer. A similar approach involves bispecific T-cell engagers (BiTEs) that bring T-cells into the tumor to kill cancer cells.
3. Precision Medicine: Cancer Genomics: DNA sequencing of cancer patients' tumors to identify specific mutations that are driving the cancer. This information guides the use of targeted therapies tailored to the genetic profile of the tumor, and also provides family counseling information for the closest relatives of these patients (if the genetic mutations are inherited).
4. Combination Therapies: Combining Immunotherapy and Targeted Therapy: Translational research has led to the development of combination treatments that use both immunotherapy and targeted drugs to enhance efficacy. Sometimes, two therapies is better than one without increasing serious side effects.
Dr. Patel: The patient I mentioned above who responded to gefitinib is a great example. It was thought that gefitinib was not effective because most patients didn't respond. Because of translational research, it was found that only those lung cancer patients who had an EGFR mutation responded to the drug and not any others. There are several other examples as well. For instance, a lab scientist once discovered a fusion protein that was seen in some lung cancer samples, called eml4-alk. Two years later, we were testing a drug targeting ALK which is now FDA approved!
How is translational research here at the Masonic Cancer Center advancing understandings of cancer and how we prevent, diagnose, and treat it?
Dr. Kolaseri: At the Masonic Cancer Center (MCC), we have multiple cutting-edge labs and a robust basic research team dedicated to understanding cancer biology, genetics, and immunology. Our translational research team works to accelerate the process of moving discoveries from the lab to clinical applications. Additionally, our experienced Clinical Trials Office ensures the efficient implementation of these trials. Our translational research prioritizes and focuses on (1) designing combination therapies whenever possible for better efficiency than using a single approach, (2) identifying mechanisms of resistance and developing second-line therapies and strategies to overcome resistance, and (3) developing minimally invasive techniques and treatments that provide quicker recovery time and improved patient outcomes.
Dr. Patel: Virtually all the work at the Masonic Cancer Center is aimed at ultimately advancing outcomes for patients with cancer. We have a breadth of laboratory science that is aimed at different aspects of cancer biology which we want to eventually translate to the clinic. Likewise, all of the clinical research is aimed at the same thing. This requires that the clinical observations we make get communicated back to our colleagues who conduct laboratory research, particularly with samples being collected and analyzed so that we can refine the approach for the next clinical trial.