MC3 Member Spotlight: Isaac Brownell, MD, PhD
Isaac Brownell, MD, PhD is a senior investigator at the National Institute of Health (NIH) who focuses on Merkel cell carcinoma (MCC). He is also an advisory board member of the MC3 Institute.
Dr. Brownell and collaborators at the NIH Intramural Research Program employed robot-assisted screening of nearly 4,000 compounds to identify potential therapeutic targets in both virus-positive and virus-negative MCC. This high-throughput approach revealed that several promising agents inhibit aurora kinases, a family of enzymes critical for proper cell division. Functional studies demonstrated that knockdown of the aurora kinase B gene impaired MCC cell survival, particularly in virus-positive tumors. Notably, treatment of mouse models with the aurora kinase B inhibitor AZD2811 not only reduced tumor burden but, in virus-positive tumors, also prevented recurrence after therapy was discontinued. These findings are both novel and clinically significant and highlight the essential role of NIH support in advancing research for rare malignancies such as MCC. 
To learn more about this research, read here: Robot-Assisted Experiments Point to Treatments for Rare Cancer | NIH Intramural Research Program
Another recent study from Dr. Brownell’s team explores the biology of spontaneous MCC regression. Using T-cell receptor (TCR) sequencing, the investigators found that tumors undergoing spontaneous regression exhibited TCR repertoire changes very similar to those seen in tumors responding to immune checkpoint inhibitor therapy. These results provide compelling evidence that spontaneous regression in MCC is driven by clonal expansion of adaptive immune responses. Beyond its biological insights, this study highlights what can be done at the NIH when clinicians are supported to investigate rare diseases and use cutting edge technologies to investigate unique events such as spontaneous tumor regression.
To learn more about this research, read here: Spontaneous tumor regression and immunotherapy response demonstrate clonal T-cell expansion in Merkel cell carcinoma - PubMed
Dr. Brownell’s research team
Back row left: Patrick Hallaert who was first author on the spontaneous tumor regression paper.
Back row right: Khalid Garman who was co-first author on the aurora kinase B paper with Tara Gelb (not pictured).
