Sapna Puri, PhD

Dr. Puri completed her graduate training in cell biology at Carnegie Mellon University, identifying mechanisms that regulate transport of proteins through the intracellular trafficking machinery. Her post doctoral training at UCSF focused on developing live imaging platforms to describe pancreas development, and understanding the rules that regulate the fate and function of the endocrine beta cell. She is currently a senior scientist in the Hebrok lab and is continuing her exploration of ways to break and fix the beta cell.

Dr. Puri’s research has been focused on understanding mechanisms that regulate the identity, functions, and expansion of the pancreatic beta cell.  Using a combination of mouse models and in vitro manipulation of beta cell lines and primary mouse and human islets, her research has uncovered a role for the hypoxia-responsive pathway in maintenance of beta cell identity.  Perturbing this pathway by stabilizing key regulatory factors leads to a loss of expression of key beta cell genes, which in turn reduces the level of insulin in these cells and cause “dedifferentiation”.  Such a loss of cellular identity naturally leads to diabetes in animal models, and the progression of this disease in the rodent models mimics what occurs in the human condition.  Dr. Puri is interested in uncovering the mechanisms that underlay such a change in beta cell identity, with the long term goal of being able to either block such a loss of function, or importantly, to reverse it.  Dedifferentiation of beta cells has been recently implicated in both Type 1 and Type 2 diabetes.  To identify regulators that are incorrectly expressed in beta cells leading to their compromised function would allow suppression of such factors and alleviation of the some of the effects of the disease.  Furthermore, Dr. Puri has spent considerable efforts in identifying the role of a specific protein in beta cell expansion.  Beta cells lose their ability to replicate as we age, and older beta cells have mechanisms in place that prevent their expansion.  In a search for ways to reverse this block in replication, Dr. Puri has characterized a mouse model that expresses increased levels of a protein called c-myc.  The expression of this protein in beta cells at levels greater than normal (but significantly lower than amounts that cause cell death) appears to trigger the replicative machinery in the beta cell and permits these cells to divide and increase in numbers, even in animals that are one year old (at which point replication is minimal).  Expression of c-myc in beta cells also impacts cellular identity, making it a key regulator of beta cell fate and function.