Goutham Narla, MD, Pardee-Gerstacker Professor in Cancer Research, talks about the challenging process of drug development, shares how his background in economics helps him succeed in his research career and discusses the importance of building strong mentoring relationships.

Your research in cancer has generated great momentum and gathered attention from the medical community and public at large. What are the latest updates on your research initiatives?
As a physician-scientist, I have had a long-standing interest in what regulates tumor cell growth; I have been investigating the specific ways tumor cells turn growth on and off through the use of proteins called oncogenes and tumor suppressors. In the beginning of my career, I spent a lot of time in the lab working on characterizing the function of tumor suppressor proteins. My subsequent goal was to develop drugs to those proteins. All of the cancer drugs we currently have on the market are aimed at turning off the accelerators of tumor growth, ultimately inhibiting the function of these oncogenes. However, we know that the other side of the coin, specifically turning on the brakes, could be equally important for cancer treatment. Over the past few years, my team has been able to develop a new class of drugs that turn the proteins back on to stop tumor cell growth and shrink tumors in mice. This discovery served as the basis for establishing an oncology start-up company called Dual Therapeutics. We hope that we will be able to dose our first cancer patient with this new class of drugs in the near future.

You were selected as the first Harrington Scholar. How has the Harrington Discovery Institute at University Hospitals in Cleveland, Ohio – part of the the Harrington Project for Discovery & Development – influenced and impacted your research?
I think the Harrington Discovery Institute has had a tremendous impact on our work. Both pharmaceutical industry and academic medicine are aligned in the pursuit of the common goal to develop better treatment options for patients. However, these two industries speak very different languages and have developed very different expertise and approaches over time. The amazing thing about the Harrington Discovery Institute is that it identifies discoveries that originated in academic medical center labs, similar to my own, and guides physician-scientists through the foreign and difficult process of drug development. There are a lot of challenging questions classically trained physician-scientists have to answer. What does it take to make a drug that is effective for a patient? What properties of the drug substance need to be optimized? How will the drug be delivered? The help and guidance that we received from the Harrington Discovery Institute has been critical in answering these questions and assisting us in bringing drugs forward with the ultimate goal being FDA approval. With the help of the Harrington Discovery Institute, we were able cut down the drug development time in half. I think that benefits everyone, and most importantly our patients.

Cancer drug development is a complicated process; what are some of the challenges that are still slowing the process down for you that you would like to see addressed on a large scale?
Drug development is incredibly challenging, as there are a lot of opportunities to move the treatment forward as well as to fail. One challenge we are faced with is we really need to understand the biology of cancer better. There are a lot of drugs that are effective in mice but they are not readily translatable or applicable to people. We need to concentrate on developing better models and be rigorous in our approach to them. We also need to think beyond developing one drug to treat one cancer, as the best cancer drugs target multiple pathways simultaneously. While the regulatory agencies and pharmaceutical companies are set up in the way that they test one drug on one patient, I think the real breakthrough will come when we combine effective cancer drugs in new, thoughtful ways, while minimizing the toxicity and side effects for our patients.  If we want to make a meaningful difference in cancer, we will not only have to identify new drugs but also create new combinations of these drugs to better target cancer.

Not many people know that before you started your career in medicine, you were interested in finance and are an economics major. How does your background in economics help you in your daily work and research activities?
I became an economics major because I originally wanted to do something completely different from my parents, who have focused their careers on science and medicine. I loved studying economics in college but then I realized that I also loved science. The economics background, however, helped me better understand what motivates people and manage risk. In order to be successful in drug development, you have to understand the economic principles behind it. We all want to develop drugs in academic medical centers, yet some of us fail to realize the high risk of failure and its incredible cost. When we understand the cost and risk involved, we will be able to speak the language of our colleagues in the pharmaceutical industry so that they get behind our scientific discoveries. Ultimately we need to learn to align exciting scientific breakthroughs with economic incentives so that we can better translate the discoveries of today into the treatments of tomorrow. In order for a pharmaceutical company to make a significant investment into drug development, they have to see the return on it. This is not greed; this is the reality of being a smart investor.

In addition, running a lab is very similar to running a small business: you have to keep track of the operating budget, manage monthly spending, assess scientific opportunities and develop an investment portfolio. While you have to be careful with your spending, you don’t want to put your funding in reserve, as that would prevent you from doing leading-edge research and moving the needle forward. Having an economics background also helps in managing risk since science truly is a risky venture, often times carrying a long-term payout.

How do you build a network of individuals that challenge and energize you to make your next discovery? How do you identify good mentors?
Your mentors should be the people who have reached the next level of professional development that you have identified for yourself, whether it is promotion, tenure, clinical expertise or scientific acumen. You should seek ways to connect with people who inspire you and are true leaders in their fields. I believe all faculty members of University Hospitals Case Medical Center have the intellectual quotient to be successful; however, great mentors are differentiated by emotional quotient: ability to be charismatic, have an engaging personality, listen and interact in meaningful ways with others.

Another group that serves as a continuous source of inspiration for me is my team. When I go into the lab and see people concentrated on their projects, it energizes me to keep up with them. Surrounding yourself with an ambitious team of individuals passionate about moving medical research forward will keep you on the edge and stimulate your professional growth.

Lastly, it is a privilege to see patients and catalyze the change in their lives by improving their health. When I am taking care of a young woman with metastatic breast cancer who is about the age of my wife, it moves me and motivates me to get up earlier in the morning to find new ways to contribute to her treatment. Patients continue to be my greatest source of motivation.

This spring you received the John S. Diekhoff Award in Mentoring. What is it that you are doing differently that makes your mentees so motivated and driven? How do you connect with them in such a meaningful way?
I think my mentorship style can be best defined as leading by example. You instill this by showing the students you are mentoring how you lead your life, care for your patients, carry out your research and treat people around you. You need to show your engagement and support through the interaction and work relationship with your mentees to communicate that you are as excited about their project as they are. You also have to identify ways to motivate your students, and incentivize them appropriately to help them realize their dreams. Finally, you have to understand that mentoring takes time; this is especially true for me as I am a big supporter of a personalized mentoring approach. You also have to be present and connected; it is impossible to establish a good mentoring relationship without going into the lab all the time, showing your support and sharing your vision and guidance.

Let’s turn things around for a bit: from a faculty member perspective, what makes a good mentee?
There should be some level of educational accomplishment; however much more importantly, a student should demonstrate motivation and ambition. I also value the ability to reach out and follow through and to be self-motivated. When students come into my lab to talk to me, I like to see that they come in prepared, they have read articles, they are conceptualizing projects they can work on and ways they can move the field forward.

A few years ago a high school student contacted me at Mount Sinai after emailing 32 other faculty members. He was hungry to get involved and work in a research lab. Every single person he contacted either ignored his emails or made it clear that he was not worth the time. When I responded to the student, I informed him that I did not have space for him in my lab but I would be happy to meet with him. The student was only in ninth grade but he came prepared, he read all of my papers, and we spent over three hours in my office discussing research. I ended up taking him in my lab. Now six years later, he is a college student with a full scholarship in Yale University, became an Intel finalist and had the honor of meeting President Barack Obama. What made me take him in my lab? His motivation when I first met him. I believe that when you put a motivated person in the right environment, great things will happen.

You have done a lot of wonderful work through the Young Scientist Foundation. You are placing high school students into labs and providing them with the unique opportunity to work with outstanding researchers and scientists. Why do you think this is important?
The Young Scientist Foundation was started by my wife, Analisa DiFeo, PhD, chef Floyd Cardoz and I. We all truly believe that education starts early in life and the right opportunity is the key to catalyzing an individual to reach his or her full potential. Today we are losing some of the most talented high school students to other fields because they just don’t have the opportunity to become involved in meaningful research and experience the impact their work can make on the scientific community. So far we have placed 37 high school students in various biomedical research labs, some of them have gone on to continue their scientific endeavors at Yale, Princeton, and Harvard. I think we all have the obligation to pay it forward for the next generation. We need to help young minds identify opportunities for growth and place talent in the right environment. We have recently started working with the inner city Cleveland high schools in partnership with the Case Western Reserve University School of Medicine to train and provide research experience to students who are not as fortunate as other kids in the area but are driven to dive into science and make an impact. While cancer research is challenging and drug development does not always pay off, I believe we will always succeed if we invest into the careers of young scientists and inspire them to lead the scientific breakthroughs of tomorrow.

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