Lawrence H. Boise, PhD

Professor

Department of Cell Biology

Professor

Department of Hematology and Medical Oncology

Office: Winship Cancer Institute, Room C4012

Phone: 404-778-4724

Email: lboise@emory.edu

Office Location:

Mailing Address:

Emory University - Winship Cancer Institute

1365 Clifton Rd. NE, Atlanta, GA 30322 1751-001-1CE

Atlanta, GA 30322

Research Focus

My research can be divided into two areas. The attached papers were from previous graduate students in each area. 

The first is designed to ask basic questions about the mechanisms of apoptosis. We had become interested in the possibility that the downstream effectors of apoptosis, caspases-3 and -7 may alter mitochondrial function independent of the release of cytochrome c; an event that is regulated by the Bcl-2 family of proteins. This was based on a paper we published in J. Biol. Chem. in 2000 where we were able to show that caspase-dependent loss of mitochondrial membrane potential could occur under conditions where cytochrome C release was blocked. This work was performed by two former graduate students in the lab (Bryan Johnson and Enrique Cepero). Henry went on to show that different caspases had distinct and sequential effects on mitochondrial function. While we are still interested in how this occurs our focus has changed to other non-apoptotic functions of effector caspases. MEFs deficient in both effector caspases are now available and we have observed differences in their adherence and motility. Additionally we believe there are differences in their ability to activate autophagy under conditions of nutrient deprivation. A graduate student who is in the Cancer Biology program at the University of Miami (Matthew Brentnall) is currently investigating the mechanisms by which these caspases regulate adhesion and motility as this could have important implications in cancer survival and metastasis and potentially explain why effector caspases are deleted in cancers despite the fact that it is generally accepted that their activation is past the "point of no return" in the apoptotic process and aren't actually required for cell death to occur. 

The second area of interest in the lab is to try to understand how the biology of being a plasma cell can be exploited in the therapeutic treatment of the plasma cell malignancy, multiple myeloma. Plasma cells are the antibody producing cells found in the bone marrow. They are long lived and have extensive endoplasmic reticulum (ER) for the production and constitutive secretion of antibodies into the bloodstream. Myeloma is a disease of transformed plasma cells and unlike many other malignancies, myeloma plasma cells retain most of the characteristics of their normal counterparts however they gain proliferative capacity. We have taken the approach that maintenance of the normal plasma cell phenotype could provide opportunities for therapeutic intervention. One drug that is FDA-approved for treatment of myeloma is the proteasome inhibitor bortezomib. We reasoned that these cells may be sensitive to proteasome inhibition because of extensive protein production and demonstrated that the unfolded protein response (UPR) and ER stress pathways are activated by proteasome inhibitors in these cells. We also reasoned that the oxidative process of protein folding may render these cells susceptible to oxidative stress and have published several papers on their response to arsenicals, including a clinical trial. Finally we can now target the survival of these cells with Bcl-2 inhibitors and are determining the factors that regulate sensitivity to one such molecule. We continue to study the apoptotic pathways induced by all of these cellular stresses and have also started to study aspects of the UPR in normal plasma cell differentiation.

Publications