Sarah Nikiforow, MD, PhD
Dana-Farber Cancer Institute in the Division of Hematologic Malignancies
Outside the lab:
Running throughout the different seasons in Boston. It’s character building!
Last good movie or book you’ve enjoyed:
As a parent with young kids, I am hard pressed to remember a movie not made by Pixar. Solzhenitsyn and Dostoyevski have taken a back seat to “Pinkalicious” recently, but I can recite that from cover to cover!
What’s your focus?
Our bone marrow transplant research group at Dana-Farber Cancer Institute is applying the Adaptive immunoseq platform in several settings. The first focus is reconstitution and differentiation of the T cell population after cord transplant, where lymphopenia is prolonged and infectious complications are significant. Building on findings of improved neutrophil and platelet engraftment, we are specifically investigating how exposure to Prostaglandin E2 impacts the diversity and turnover of the T cell repertoire after double umbilical cord transplantation. Ex vivo manipulation prior to stem cell infusion to allow use of a single cord and decrease infections would have significant clinical impact.
The second focus is chronic graft versus host disease, a significant cause of disability and mortality in stem cell transplant recipients. Current preventative and treatment strategies are of limited utility. Regulatory T cells have been shown to play a role in preventing and ameliorating GvHD; we have previously shown a potential therapeutic role for low-dose interleukin 2 which expands this population. Our objective is to identify differences in reconstitution of regulatory T and conventional T cell repertoires in stem cell recipients with and without chronic GvHD, both with and without exposure to interleukin 2. We will gain insights into the basic immunology of Treg differentiation and into potential biologic and cellular therapies for chronic GvHD
How has immunoSEQ helped in your research?
The process of engraftment, thymic homing, differentiation, and expansion of lymphocytes post stem cell transplant is extremely dynamic. The ability to identify individual T cell clones, assess the diversity of a given population, and track turnover of dominant clones yields greater insights into these processes over time than can measurements of T cell percentages and numbers by flow cytometry.
So what did you think?
The scientists and statisticians at Adaptive have been extremely helpful in individualizing the process to our samples and clinical questions. It has been an active learning process on both sides. The assistance has not ended with generation of sequences but continued through discussion of what statistical analyses would be most enlightening in different clinical contexts. Adaptive has become an active collaborator in some aspects of our investigations.
A pleasant surprise was the bidirectionality of our conversations and the investment that Adaptive has shown in generating reproducibly high quality data from our samples. The second surprise was exactly how many questions can be asked and how many different manipulations are possible once TCR sequence data is generated.
When do you anticipate submitting your findings?
We have submitted an abstract on our findings in the umbilical cord setting to the Tandem meetings in February, 2013. We anticipate submitting findings on the regulatory T cell reconstitution in the next 6 months.