Irma Husain, MBBS
Irma Husain, MBBS
2021 Ben J. Lipps Research Fellowship Award
Institution: Duke University Hospital
Project Title: Role of Macrophage AIF-1 in Ischemia Reperfusion Injury and Kidney Allograft Rejection.
How would you sum up your research in one sentence?
My research dives into dissecting the role of macrophages and their specific therapeutic targets in ischemia reperfusion injury and kidney allograft rejection in transplantation.
Provide a brief overview of the research you will conduct with help from the grant.
During acute rejection, macrophages account for a major population of infiltrating leukocytes in human allograft biopsies and their depletion has shown some protective effect. However, given their plasticity and heterogeneity they play numerous roles including tissue repair and regeneration. Therefore, an ideal target would be one that can be used to selectively dampen inflammatory macrophages while promoting reparative ones. This is why I am interested in exploring a protein known as Allograft Inflammatory Factor-1 (AIF-1), initially identified in inflammatory macrophages infiltrating rejecting cardiac allografts. Based on my preliminary data, I hypothesize that AIF-1 is a critical mediator of macrophage function during ischemic injury thereby promoting kidney inflammation. Furthermore, following kidney transplantation, it promotes intra-graft macrophage mediated T-cell activation and aggravates allograft injury. Therefore, inhibition of AIF-1 will result in ameliorating both ischemia-reperfusion injury and acute rejection, and increase graft longevity. To this end, I will be using murine AIF-1 knock outs, both global and cell specific, in a mismatched kidney transplantation model to illicit and target allograft rejection.
What impact do you hope your research will have on patients?
Although much progress has been made in the field of transplantation, current immunosuppression therapies have significant side effects including metabolic disorders, infections and nephrotoxicity. Furthermore, long term allograft survival has only marginally improved despite significant reduction in incidence of acute rejection. Newer targets, possibly those directed towards innate immune cells (e.g. macrophages) may have the potential to prolong allograft survival for kidney transplant recipients. This should have multiple downstream beneficial effects both for the kidney recipients and others waiting on recipient lists.
What are your career goals at the end of the grant period? Five years out? Ten years out?
Through this grant, in the short-term, I hope to develop the skills to design, conduct and troubleshoot my experiments and learn novel research methodologies. In the long term, I aspire to be a Transplant Nephrologist physician-scientist. I hope to make a significant contribution to the field through cutting edge research and leadership roles as a researcher together with positively impacting clinical patient care as a clinician.
What inspired you to focus your research in this area?
Increments in quantity and quality of life of transplant recipients can be achieved through prolonging allograft survival and minimizing immunosuppression side effects. I believe that recent attention to the role of innate immune cells in allograft survival has brought forward the need to develop therapeutics targets for them. With inspiring mentorship from Dr. Xunrong Luo and support from Dr. Allan Kirk, I have been able to take up these laboratory endeavors.
Something you may not know about me is…
I'm always on the hunt for fascinating SCUBA diving destinations
In my free time I like to…
Tend to my garden and many house plants, experiment with cooking and enjoy the company of my adorable pets (a cat, a dog and fish)