Description of Research Expertise

Research Interests:

Plasma cell differentiation, B cell development

Research Summary


In my laboratory we study several aspects of antibody-secreting plasma cells. Plasma cells are the main source of antibodies throughout the body, and thus play essential roles in host protection. Yet, plasma cells can also endanger health in a variety of scenarios including chronic transplant rejection, autoimmunity, and multiple myeloma. Our ultimate goals are to define the unique biosynthetic pathways used by plasma cells to survive and achieve and maintain antibody titers, and to use this information to eliminate pathogenic plasma cells.

Plasma cells are unique cells: This is due to their capacity to secrete exceptionally large quantities of antibodies, and their ability to persist as exceptionally long-lived cells. A chief question driving our work is how pathways needed for high throughput antibody synthesis intersect with life and death decisions in these cells.

Current projects in the lab include studies designed to address these questions:

1. How to activate B cells divide and build up the endoplasmic reticulum (ER), as needed to secrete large quantities of antibodies, without dying? Here we are focusing on a variety of poorly studied regulators of ER function in B cells and plasma cells.
2. How do established (long-lived and non-dividing) plasma cells regulate ER function to maintain antibody titers? How do these processes differ in normal plasma cells versus malignant plasma cells? On the last point we are leveraging a variety of mouse models and a xenotransplant model we devised that supports the survival of human plasma cells harvested from normal donors and patients with multiple myeloma.
3. How do plasma cell extrinsic factors available in the bone marrow influence ER function and therefore plasma cell survival? For this point we are building on our recent results (derived from a collaboration with NIH investigator Avinash Bhandoola) revealing that plasma cells maintain ER homeostasis by using purinergic receptors to perceive extracellular ATP in bone marrow microenvironments.

Recent selected publications:

1. Ishikawa, M., Z. S. Hasanali, Y. Zhao, A. Das, M. Lavaert, C. J. Roman, J. Londregan, D. Allman, and A. Bhandoola. 2024. Bone marrow plasma cells require P2RX4 to sense extracellular ATP. Nature 626: 1102-1107.
2. Hasanali, Z. S., A. L. Garfall, L. Burzenski, L. D. Shultz, Y. Tang, S. Kadu, N. C. Sheppard, W. Liu, D. Dopkin, D. T. Vogl, A. D. Cohen, A. J. Waxman, S. P. Susanibar-Adaniya, M. Carroll, E. A. Stadtmauer, and D. Allman. 2024. Human IL-6 fosters long-term engraftment of patient-derived disease-driving myeloma cells in immunodeficient mice. JCI Insight 9.
3. Gaudette, B. T., C. J. Roman, T. A. Ochoa, D. Gomez Atria, D. D. Jones, C. W. Siebel, I. Maillard, and D. Allman. 2021. Resting innate-like B cells leverage sustained Notch2/mTORC1 signaling to achieve rapid and mitosis-independent plasma cell differentiation. J Clin Invest 131: 151975-151992.
4. Gaudette, B. T., D. D. Jones, A. Bortnick, Y. Argon, and D. Allman. 2020. mTORC1 coordinates an immediate unfolded protein response-related transcriptome in activated B cells preceding antibody secretion. Nat Commun 11: 723-739.
5. Jones, D. D., B. T. Gaudette, J. R. Wilmore, I. Chernova, A. Bortnick, B. M. Weiss, and D. Allman. 2016. mTOR has distinct functions in generating versus sustaining humoral immunity. J Clin Invest 126: 4250-4261.