Name: Ali Poyan Mehr, MD

Institution: Beth Israel Deaconess Medical Center

Grant: Carl W. Gottschalk Research Scholar Grant (2018)

Project Title:  Metabolic and Molecular Predictors of Acute Kidney Injury in Humans and Their Clinical Response to NAD+ Augmentation
 

How would you sum up your research in one sentence?

• Our group is interested in understanding metabolic mechanisms by which the normal kidney resists different kinds of stress. Our hope is that such understanding can perhaps help reduce the burden of AKI.

Provide a brief overview of the research you will conduct with help from the grant.

• Based on preclinical studies by Dr. Samir Parikh’s group at BIDMC, the mitochondrial biogenesis regulator PGC1α was shown to exert a protective effect against acute kidney injury (AKI) through the biosynthesis of NAD+. Through the support I am receiving from the ASN Foundation, our group will study the role of NAD+ biosynthesis in human AKI, including the presence of enzymatic dysregulation, metabolic signatures, and potential therapeutic targets. These are some of the questions I hope to address, in part by conducting a multi-center randomized, placebo-controlled clinical trial examining the safety and efficacy of NAD+ augmentation in preventing AKI.

What inspired you to focus your research in this area?

• In addition to the tremendous morbidity and mortality associated with AKI, we have no targeted therapy to prevent or alleviate AKI. When Samir's group reported the findings around NAD+ and the kidney in Nature two years ago, we thought there was an urgent need to examine this pathway in patients. If we can identify susceptible individuals based on their unique patterns of NAD+ metabolism and enhance their resistance to stress by manipulating NAD+, this could be an important advance for patients.

What impact do you hope your research will have on patients?

• My hope is that the studies we will be conducting over the next few years will help further advance our understanding of human AKI. This may include increasing our precision in the identification of “at risk” patients and help decrease the burden of AKI through targeted therapeutics.

What are your short- and long-term career goals?

• My short-term goals is to become a well-trained clinical trialist in nephrology, identify and work with collaborators who are interested in studying AKI. and successfully implement our studies. My long-term goal is to make an impact in patients by translating preclinical science to the bedside

What has surprised you most about your career?

• Serendipity is real. As an exchange student, I had the fortune to join John Forrest’s lab at Yale. At that time, I neither had imagined a career in nephrology nor the possibility of migrating to the U.S. Those who know John Forrest also know the influence he has exerted on careers of dozens, perhaps hundreds of students and trainees. So, I stayed and trained to become a nephrologist. During my post-graduate training at BIDMC, my career was marked by several unexpected turns and events. At the very start were Drs. M. Zeidel, V. Sukhatme, and A. Karumanchi, who interviewed me for a physician-scientist track, granted me the opportunity to train at the BIDMC, and continue to provide mentorship and support to this date. By the time I entered the nephrology fellowship training Dr. M. Pollak had arrived to take over the leadership of the division of nephrology. It was his ongoing support and mentorship which encouraged me to pursue my desire to train as a physician-scientist and enabled me to remain in one of the most stimulating academic environments. Among the most influential moments in this environment, was the time when Samir and I met to discuss the opportunity of translational research in AKI. Since then, Samir’s mentorship and guidance has not only enabled me to pursue translational research studies and secure two consecutive awards in the field of clinical AKI research (CAO Award from BIDMC and this prestigious ASN Foundation Award), but has created the foundation for my career as a clinical trialist. None of the turning points could have been foreseen.

What advice would you give to others to encourage them to apply for this grant funding?

• Identify a scientific domain which is close to your heart, find strong mentors who will support your aspirations, work hard to collect preliminary data. All else will fall into place, soon or later.

In my free time I like to…

• Spend time with my wife on various activities, including cooking, gardening, and reading.