Programs > Fellowships > Fellows > June 2009 > Diego Acosta-Alvear, Ph.D.

Diego Acosta-Alvear, Ph.D.
University of California, San Francisco - Howard Hughes Medical Institute
San Francisco, CA

Project Title: Regulation of the unfolded protein response in multiple myeloma
Sponsor: Peter Walter, Ph.D. 

Multiple myeloma is an aggressive, incurable blood disease with poor survival rates and approximately 20,000 cases per year in the United States. While therapeutic improvements have been made in the last decade, the disease remains incurable and the patients eventually succumb after becoming refractory to currently available treatments. Moreover, the biological cause(s) of the disease remain poorly understood.  It is known that an essential mechanism called the unfolded protein response (UPR) is involved in protein synthesis for normal cellular functions, such as growth, communication, and survival. Therefore, a tight regulation of the UPR is a critical part of normal cell physiology.  Accumulating evidence posits that some UPR components promote the survival of cancer cells and thus may contribute to myeloma progression.

Dr. Acosta-Alvear will investigate the activation and regulation of UPR in multiple myeloma cells.  He aims to establish molecular signatures associated with aberrant regulation of the UPR in multiple myeloma and to develop biochemical tools to manipulate the UPR to restrain tumor progression.  By demonstrating that the UPR is instrumental to multiple myeloma survival, he may justify its exploitation as a valid target for developing therapeutics.  These findings may also be extended to other types of tumors, as accumulating evidence links UPR to cell survival in other cancers.

What is the unfolded protein response (UPR)?

The UPR is a conserved signaling cascade that exists in every cell and is in charge of telling the cell whether or not there is stress in a critical organelle called the "endoplasmic reticulum".  The endoplasmic reticulum is an essential place in the cell where all the synthesis and processing of important proteins happens.  If there is stress in the endoplasmic reticulum, the UPR takes measures to correct this stress.  We have been studying the UPR for the past 15 years, but it is only recently that it has been linked to many diseases.  We are interested in understanding how the regulation of the UPR contributes to the pathogenesis of cancer, and in particular multiple myeloma.

What is the connection that the UPR has with multiple myeloma?

Multiple myeloma is a very rare blood disease that arises from antibody-secreting plasma cells.  Plasma cells are responsible for making antibodies that travel around the body fighting infection; the production of antibodies is a very demanding process that occurs in the endoplasmic reticulum.  Plasma cells therefore need a very active endoplasmic reticulum in order to make the antibody molecules and thus the UPR is essential to their physiology.  Sometimes plasma cells can have a mutation the transforms them into a melignant cell, which in this case turns into myeloma.  These malignant plasma cells grow without restraint and cause the typical pathological problems associated with multiple myeloma.  That is why we are interested in studying the UPR, because the UPR is essential for the differentiation of normal plasma cells and its regulation might be critical for the pathogenesis of malignant plasma cells which are the myeloma cells.

How did you become interested in immunology research?

During my Ph.D., I was working on cellular differentiation and from those studies found out that some stress control mechanisms are also regulated during the differentiation process, one of these the UPR.  I became very interested in understanding how this essential signaling cascade played a role in other cellular contexts.  The link between UPR and the immune system is an inherent one, which means that a misregulated UPR can negatively affect the immune system.  When I joined this lab, I turned my focus into how the UPR is related to multiple myeloma and am now interested in understanding how the UPR controls the physiology and pathology of this cancer.

I’m originally from South America; I was born in Ecuador.  My father has a private practice in Ecuador as a lawyer and my mother is an ambassador for Ecuador to foreign countries.  She’s now performing her duties as ambassador in Bolivia.  Because of the constant travelling due to their jobs I ended up studying biology in Columbia and I moved to the U.S. to pursue my graduate education.  In my free time I like to play the electric base guitar and also have a passion for building guitars.  I enjoy going out to dinner with my wife and testing new foods and restaurants around town.