Investigator Spotlight: April 2016
Alexandra Butler, MBBS
Dr. Butler is an adjunct professor of medicine and endocrinology at City of Hope National Medical Center in Duarte, California. Dr. Butler joined nPOD in 2015.
- Tell us about your education and background – where are you from, where did you go to school?
My childhood was split between the US and the UK, and I have family on both sides of the Atlantic. The bulk of my school years were spent in England and, subsequently, I went to medical school at the University of Newcastle upon Tyne in northern England. A few years later, I moved to the Mayo Clinic in Rochester, Minnesota to do a Pathology residency.
- Where do you currently work and what is your position? What does a “day in the life” look like for you?
Currently, I am an adjunct professor of medicine/endocrinology City of Hope National Medical Center in Duarte, California. Prior to that I was at the University of California, Los Angeles for 12 years. Typically, I split my time between doing microscopy and analysis of pancreas tissue sections, planning projects, supervising students and writing.
- Why diabetes? How did you get involved in diabetes and/or what made you want to work in diabetes research?
When I was a pathology resident, I became aware that the pancreas was an overlooked organ. At a routine autopsy, only a small piece of the tail of pancreas is collected for microscopic analysis. Because of this, a great deal of information has traditionally been lost, particularly as we know that changes in the pancreas organ are frequently patchy rather than homogeneous .
- Tell us about your research.
My research is interested in the regenerative capacity of human endocrine cells in human pancreas. Chromogranin A is a global marker of endocrine cells. Most endocrine cells in the pancreas, in addition to Chromogranin A, also express other hormones, Insulin and Glucagon being most frequent, with Pancreatic Polypeptide, Somatostatin and Ghrelin in smaller numbers of endocrine cells. We have found that in adult human pancreas a small number of pancreatic endocrine cells (<1% of the total number) express Chromogranin A, but not any of the other known pancreatic hormones; we have termed these cells Chromogranin Positive Hormone Negative [CPHN] cells. We found that there is a very high percentage of CPHN cells in sections from human fetus and newborn pancreas, which suggests that these cells are a precursor of mature endocrine cells. We also found that the percentage of CPHN cells is higher in pancreas from both type 1 and type 2 diabetic subjects, suggesting that this may be an attempt at restoring the beta cells lost as a consequence of the disease. Additionally, our observations that these cells occur most commonly in small clusters of 1-3 cells rather than in established islets, suggesting that these cells may be newly formed endocrine cells. The source of these CPHN cells is of great interest, as they could potentially occur de novo (neogenesis), by transformation of existing cells (transdifferentiation) such as from cells in the ducts or exocrine pancreas, or by replication of existing endocrine cells. Our goal is to characterize these cells by looking at the frequency of replication and apoptosis, and relevant transcription factors in the CPHN cell population. Our findings will have significance with regard to the regenerative capacity of human endocrine cells in human pancreas.
- What are your thoughts on the progress being made in T1D research as a whole?I think this is a very exciting time to be involved in diabetes research, as there are so many new tools available to us to study the pancreas in both health and disease states. However, in order to utilize those tools effectively, it is important to have high quality human pancreas available to study, and this is where the JDRF nPOD consortium has created an unparalleled resource for researchers.
- Why is diabetes research so important?
Type 1 diabetes afflicts 5-10% (approximately 1 million people) of the diagnosed diabetic population in the United States. The incidence of both type 1 and type 2 diabetes is increasing, so it is critical to better understand the underlying causes and mechanisms of disease induction and progression in order to develop strategies to ameliorate and prevent the burden these lifelong diseases have on both the individual patient, their families and our healthcare system.
- Do you have anything extra you would like to share? Is there anyone to thank or acknowledge?
I would like to thank the donor patients and families whose insightful generosity has enabled the nPOD program to grow and thrive. In addition, the funding support from the JDRF has been instrumental in supporting the vision underlying the nPod program and bringing it to fruition. It is a testament to the program’s success that so many researchers from around the country and the world now consider the tissue provided by nPod to be a central facet in their research efforts.
- When you’re not working, what do you like to do for fun?
I love to be outdoors, and so I am very fortunate to live in southern California where outdoor recreation is enjoyable all year round. I enjoy running, hiking in the hills and biking.