Larry Boise, PhD


Larry Boise, PhD

Professor, Department of Hematology and Medical Oncology, School of Medicine

Professor, Department of Cell Biology, School of Medicine

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Graduate Programs

  • Full Member - Biochemistry, Cell and Developmental Biology
  • Full Member - Cancer Biology
  • Full Member - Immunology and Molecular Pathogenesis

Education

PhD, Virginia Commonwealth University, 1991

Contact Information

Email: lboise@emory.edu

Phone: 404-778-4724

Address:
Winship Cancer Institute, Room C4078 1365-C Clifton Road NE Atlanta, GA 30322 1751-001-1CE

An 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.

A second interest in the lab is understanding what the intrinsic and extrinsic signals are that control myeloma cell survival, how they are regulated and can influence therapeutic response. Our focus on intrinsic signals are primarily on the BCL2 family of apoptotic regulators. We study what determines why some cells may be dependent on one family member for survival and other cells on a different family member. This can be influenced both genetic (chromosomal translocations) and epigenetic (differentiation state) of the cell. Moreover, it can also be influenced by signals from other cells in the bone marrow micro-environment such as mesenchymal derived stromal cells or cytokines (IL6). We study how these and other signals influence BCL2 dependency and cell survival and influence response to therapy. This includes modern immunotherapy such as CAR-T cells.

Diversity: Inclusion in the Modern Workplace, 2021
Unconscious Bias Training, 2022
Diversity: Inclusion in the Modern Workplace, 2022

James Ackley

James Ackley

Cancer Biology

Entrance Year: 2018

Topic: Determining the role of the stromal micro-environment and mitochondrial apoptotic pathway in CAR-T function in multiple myeloma

Karan Bhatia

Karan Bhatia (he/him)

Cancer Biology

Entrance Year: 2023

Topic: Modeling the evolution of drug tolerant persisters in AML.

Vero Canarte

Vero Canarte (she/her)

Cancer Biology

Entrance Year: 2020

Topic: Role of CD28/CD86 signaling in the survival of Multiple Myeloma

David Weir

Cancer Biology

PhD, 2022

"CHARACTERIZATION OF CELL DEATH IN CASP3-DEFICIENT MOUSE EMBRYONIC FIBROBLASTS"


Tyler Moser-Katz

Biochemistry, Cell and Developmental Biology

PhD, 2022

"The Role of CD86 Trafficking and Signaling on Myeloma Survival and Proliferation"


Katelyn Ponder

Cancer Biology

PhD, 2018

"Mechanism of caspase-3 activation and Mcl-1 inhibition in the regulation of apoptosis"


Jason Conage-Pough

Cancer Biology

PhD, 2018

"Characterization of Constitutive BIM Phosphorylation in Plasma Cell Malignancies"


Catherine Ann Gavile

Immunology and Molecular Pathogenesis

PhD, 2017

"The role of the CD28-CD86 signaling module in maintaining myeloma cell viability"


Shardule Shah

Immunology and Molecular Pathogenesis

PhD, 2016

"Heat Shock Factor 1 Regulation in Multiple Myeloma Pathogenesis"


Brian Gaudette

Immunology and Molecular Pathogenesis

PhD, 2014

"Characterization of cell stress pathways in normal and abnormal plasma cells"