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Faculty Profile: Michael Ison, MD, MS, professor of Medicine in the Division of Infectious Diseases and of Surgery in the Division of Organ Transplantation

Michael Ison, MD, MS

Michael Ison, MD, MS, is a professor of Medicine in the Division of Infectious Diseases and of Surgery in the Division of Organ Transplantation. He is also director of the Northwestern University Clinical and Translational Sciences Institute’s Center for Clinical Research.

His clinical and research interests focus on infections in transplant recipients, as well as viral infections including norovirus, cytomegalovirus and respiratory viral infections (influenza and adenovirus) in this patient population. He is also involved in collaborative research efforts aimed to identify variants of the SARS-CoV-2 virus as they emerge in Chicago and in helping to develop biobanks of specimens from patients with COVID-19.

Ison is also a member of the Northwestern University Transplant Outcomes Research Collaboration (NUTORC) and the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

What are your research interests?

My research focuses on two major areas of infections. My primary research focus is on respiratory viral infections in hospitalized and immunocompromised adults. Historically this has focused on influenza but has expanded to include RSV and COVID-19 more recently. We have worked diligently to develop and implement antiviral drugs to prevent and treat influenza and other respiratory viral infections. Through this work, we have demonstrated that oseltamivir is safe and effective for the prevention of influenza in immunocompromised patients and I have led key studies that led to licensure of peramivir and baloxavir for influenza. My second area of research is on post-transplant infections. We currently are leading a large multi-center study to identify the natural history and optimal treatment of norovirus in transplant patients, a debilitating and chronic disease in these patients.

What is the ultimate goal of your research?

My goal is to develop antiviral strategies for the prevention and treatment of a range of respiratory and non-respiratory viruses affecting hospitalized and immunocompromised adults. Unfortunately, as we have seen this past year, new pathogens remain a persistent threat to the health of mankind. Lessons gleaned from our ongoing work helped have informed our approach to research (the NUCATS-funded COVID-19 Biobank and Lurie Cancer Center-funded COVID-19 Convalescent Biobank), have provided tools for our ongoing research (I was part of the interagency working group that developed the Ordinal Scale being used for most COVID-19 hospitalized studies) and inform approaches to improve outcomes of infection. Likewise, antimicrobial resistance is a persistent threat in infectious diseases and impacts the success of antiviral drugs. Developing therapies that can be applied in ways to prevent resistance emergence while maintaining clinical efficacy is the ultimate goal of any infectious diseases research.

How did you become interested in this area of research?

I think mentors are critically important to interest in research. When I met with faculty at the University of Virginia to investigate potential research projects, my eventual mentor Fred Hayden proposed a series of studies using an immunocompromised mouse model of influenza and a series of clinical studies in humans. He set me up with two amazing collaborators: Larisa Gubareva, who is one of the world’s experts on influenza antiviral resistance and now the Lead of Molecular Epidemiology at the CDC’s Influenza Division, and Tom Braciale, who was the director of the Carter Immunology Center at the University of Virginia.

These mentors introduced me and facilitated my excitement about influenza and its unique impact on immunocompromised patients. They also connected me with the National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group where I learned how to collaborate with others to design multi-center clinical trials of antivirals for respiratory infections. I continued this interest to Massachusetts General Hospital where I worked with Jay Fishman during my Transplant Infectious Diseases Fellowship. We conducted the first study of the impact of oseltamivir on lung transplant recipients. Clinically, Jay also sparked my interest in viral infections outside the lung, as well. As the result of a unique case during my year in Boston, we established the U.S. Organ Vigilance System (OPTN Disease Transmission Advisory Committee), which helped focus my interest in donor-derived infections.

What types of collaborations are you engaged in across campus (and beyond)?

I love collaborative research — it’s always more fun to do research with a group than by yourself. Perhaps one of the most exciting times for me at Northwestern was when Daniela Ladner joined the transplant group and established NUTORC. This brought together clinical and non-clinical researchers to solve problems relevant to transplant. The initial presentations were incredibly exciting and engaging and led to a number of projected, including a NIH-funded study to optimize education about donor risk. My research has been inherently collaborative. There is nearly nothing I am working on that I can do myself; the infrequent infections and unique populations I study required a team effort. Several years ago, we began putting two collaborations together, one focused on our norovirus study and another focused on influenza vaccination in the transplant populations. Both brought transplant infectious disease leaders from some of the largest transplant programs together to solve common problems and each garnered NIH funding. They also set up platforms for future studies that are now in the planning stages.

2020 has been a challenging but exciting year in terms of collaborations. Due to ongoing work on COVID-19, I’ve had the chance to interact with a superstar group in Infectious Diseases (Judd Hultquist, Lacy Simons, Ramon Lorenzo Redondo and Egon Ozer) who have led efforts to identify variants as they emerge in Chicago and truly made the COVID-19 Biobank happen. I have also worked with researchers in nephrology, cardiology and immunology to understand the impact of COVID-19 on humoral response and outcomes of COVID-19.

I was also lucky to be asked to lead the NUCATS Center for Clinical Research, which has resulted in a significant expansion of collaborations across campus. What is has shown is how many incredible resources are out there for clinical researchers to leverage to optimize their research. I’ve met and begun working with a huge number of people who I hadn’t work with previously. It’s been exciting to learn and build innovative ways to improve recruitment and retention of subjects, to engage a larger pool of potential subjects and, most importantly, move our research beyond the confines of NMH.

How is your research funded?

My research is funded through a number of approaches. Our current norovirus project and our influenza vaccine studies are funded by the NIH, as have several prior projects. I have worked with a range of pharmaceutical companies to perform clinical trials, including several as the lead investigator that helped to design and implement large multi-national research studies. Some of my most interesting research has been funded by the hard work of summer students, residents and fellows. These projects significantly advanced our epidemiologic understanding of critical infections such as norovirus, influenza, respiratory syncytial virus and parainfluenza virus. This data has been used by the interagency working group on endpoints of influenza antiviral studies and to inform NIH-funded studies.

Where has your work been published?

The past year has resulted in several high impact publications. The CAPSTONE-2 study that expanded the indication of baloxvir was recently published in Lancet Infectious Diseases. A summary of 10 years of experience with the organ vigilance system was published in American Journal of Transplantation. We also published a five-year experience on what we’ve learned about optimal screening of candidates and recipients of lung transplant to prevent development of Ureaplasma-associated hyperammonemia syndrome in Clinical Infectious Diseases. We’ve also had great team science published this year related to COVID-19 clades in Chicago in >EBioMedicine.