Dr. Goutham Narla - Reactivating an Enzyme's Function to Treat Disease

March 10, 2020

Goutham Narla, MD, PhD, Chief and Associate Professor in the Division of Genetic Medicine and member of the Rogel Cancer Center, is a medical geneticist who specializes in the care of high-risk cancer patients, including prostate, breast, ovarian, and colon cancer patients. Dr. Narla's current research focuses on the identification and characterization of the key negative regulators, tumor suppressor proteins of cancer development and progression, and the development of small molecule-based therapies that activate tumor suppressor genes. He pursues these research areas avidly with the hope of translating his lab’s findings into the development of new classes of drugs for disease treatment. Teaching is also a passion of Dr. Narla's. He co-founded the Young Scientist Foundation which teaches and mentors high school students and helps them to see the possibilities of a career in science, and is proud of the many graduate and undergraduate students he's worked with during his research career. In addition, Dr. Narla serves as an Associate Director of the University of Michigan Medical Scientist Training Program (MSTP).

Behind the Scenes with Dr. Goutham Narla

Dr. Goutham Narla

What is your research about?

My laboratory is focused on understanding the mechanisms of protein phosphatase 2A (PP2A) dysregulation across a range of disease processes including cancer, and on the development of small molecule modulators of PP2A as novel therapeutic strategies for cancer treatment.

I am currently interested in defining the mutational spectrum and mechanisms of PP2A inactivation in a wide range of human cancers, identifying novel PP2A substrates and regulated pathways in cellular and in vivo model systems, and exploring the translational potential of novel series of small molecule direct activators of PP2A in a series of cellular and in vivo models.

We have generated a series of genetically engineered models (GEM) with knock-in mutations of recurrent PP2A mutations that have been identified in human cancer. We are looking to characterize the phenotype of these mouse models and cross them to various tumor-prone mice.

Additionally, we have solved a high resolution cryo-EM structure of one of these small molecules bound to the heterotrimeric PP2A holoenzyme and are utilizing this information to better understand the mechanisms regulating PP2A biogenesis and in the development of novel classes of chemical modulators of distinct holoenzymes.

Dr. Narla has published over 90 papers - you can find his most recent one highlighted below:

U-M Research Suggests Studies of a Key Tumor Suppressor Protein Need a Second Look

What is the goal of your research?

The ultimate goal of our research is to leverage our knowledge and understanding of the mechanisms underlying PP2A’s pathological inactivation to develop novel drugs to restore its function which could result in the treatment of a broad range of diseases.

Why is this area of research important to you?

I am interested in this area of research because, to date, the study of the negative regulators of protein phosphorylation, specifically protein phosphatases, has been a neglected area in cell biology. These “brakes” on cell growth and cell division represent critical enzymes in the regulation of diverse cellular processes that are hijacked in a wide variety of human disease including cancer. My hope is that by better understanding the processes regulating this fundamentally important class of enzymes at the structural, biochemical, and biological level, we can develop tailored, therapeutic strategies to reactivate them for the treatment of disease.

What are your clinical interests?

I am a medical geneticist and the Chief of the Division of Genetic Medicine in the Department of Internal Medicine. My clinical interests are in the care of high-risk cancer and medical genetics patients. I oversee a division that cares for over 4,000 genetics patients per year and it has been an honor to help lead this division in the care of these highly complex patients.

How did you become interested in this area?

One of the first patients that I ever cared for as a medical resident was a young woman who came in with acute shortness of breath and widely metastatic breast cancer. She was only 34-years-old. She quickly succumbed to her disease and I will never forget the feeling of losing such a young woman to breast cancer. I immediately became very interested in understanding the genetic basis of cancer and how inherited variants in genes like BRCA1 or 2 can predispose our patients to developing cancer at a young age.

What accomplishment are you most proud of?

I am most proud of having trained 9 graduate students and 16 undergraduate students during my research career. Many of them have gone on to medical school, graduate school, or MSTP programs, and the graduate students that I have trained continue to be involved in academic medicine and research. My trainees challenge and inspire me on a daily basis and I am forever grateful for the opportunity to teach them and yet at the same time learn from them.

What advice would you give to someone who is considering specializing in genetic medicine?

I would tell anybody interested in the field of genetic medicine that there has never been a time of a greater outpouring of knowledge about the hereditary basis of disease. Large scale sequencing efforts and fundamental biology have allowed us, with greater certainty, to pinpoint the exact DNA changes that cause diseases ranging from Marfan syndrome to breast cancer. Importantly, that knowledge has now been leveraged in many cases to the development and approval of specific drugs directed at these pathways and have allowed health care providers to treat patients in a personalized manner.

Who has inspired you the most?

My parents, both of who are in the medical field, inspire me every day and have shown me through their love of medicine and science that this is the most amazing career in the world. My wife is a world-renowned scientist and I am forever grateful for her support, inspiration, and collaboration on many projects that are labs work on together.

How do you balance your work and personal life?

My three amazing children constantly remind me of the importance of work-life balance. I work smarter than ever – I am more efficient, more focused, and more determined when I come to work because of them. I know that come 5 pm, I want to leave to pick them up, make dinner, and spend time with them.

What five words best describe you?

Driven, empathetic, creative, compulsive, and resilient.

More about Dr. Narla…

You can read more about his research at Michigan Research Experts.

You can keep up with what he and his lab are doing on twitter @gouthamnarla and @NarlaLabUMich.