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David Michael Allman, Ph.D.
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Professor of Pathology and Laboratory Medicine
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Associate Director, Abramson Cancer Center Flow Cytometry Core Facility, University of Pennsylvania
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Vice Chair for Faculty Development, Dept. of Pathology & lab Medicine
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Department: Pathology and Laboratory Medicine
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Graduate Group Affiliations
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- Immunology 6a
- Pharmacology e
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Contact information
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230 John Morgan Building
3a 3620 Hamilton Walk
Philadelphia, PA 19104-6082
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3a 3620 Hamilton Walk
Philadelphia, PA 19104-6082
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Office: (215) 746-5547
34 Fax: (215) 573-2350
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34 Fax: (215) 573-2350
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Email:
dallman@mail.med.upenn.edu
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dallman@mail.med.upenn.edu
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Publications
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Links
c7 Search PubMed for articles
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c7 Search PubMed for articles
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Education:
21 9 B.S. 19 (Microbiology) c
36 Pennsylvania State University, 1982.
21 a Ph.D. 17 (Immunology) c
33 University of Pennsylvania, 1993.
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Permanent link21 9 B.S. 19 (Microbiology) c
36 Pennsylvania State University, 1982.
21 a Ph.D. 17 (Immunology) c
33 University of Pennsylvania, 1993.
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38 Plasma cell differentiation, B cell development
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18 Research Summary
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22b 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.
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156 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.
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58 Current projects in the lab include studies designed to address these questions:
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106 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.
1a5 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.
195 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.
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26 Recent selected publications:
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dd 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.
170 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.
131 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.
ef 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.
de 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.
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Description of Research Expertise
24 Research Interests:8
38 Plasma cell differentiation, B cell development
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18 Research Summary
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22b 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.
8
156 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.
8
58 Current projects in the lab include studies designed to address these questions:
8
106 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.
1a5 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.
195 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.
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26 Recent selected publications:
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dd 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.
170 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.
131 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.
ef 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.
de 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.
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18d Pongubala JM, Northrup DL, Lancki DW, Medina KL, Treiber T, Bertolino E, Thomas M, Grosschedl R, **Allman D, **Singh H : Transcription factor EBF restricts alternative lineage options and promotes B cell fate commitment independently of Pax5. Nature Immunol. 9(2): 203-215, February 2008 Notes: ** Shared senior authorship
10d Lindsley RC, Thomas M, Srivastava B, Allman D: Generation of peripheral B cells occurs via two spatially and temporally distinct pathways. Blood 109(6): 2521-8, March 2007 Notes: Epub 2006 Nov 14.
5d Thomas M, Calamito M, Srivastava B, Maillard I, 13 Pear WS, Allman D bb : Notch activity synergizes with B cell receptor and CD40 signaling to enhance B cell activation. Blood 109(8): 3342-50, April 2007 Notes: Epub 2006 Dec 19.
12d Allman D, Dalod M, Asselin-Paturel C, Delale T, Robbins SH, Trinchieri G, Biron CA, Kastner P, Chan S: Ikaros is required for plasmacytoid dendritic cell differentiation. Blood 108(13): 4025-34, Dec 2006 Notes: Epub 2006 Aug 15.
100 Harman BC, Miller JP, Nikbakht N, Gerstein R, Allman D: Mouse plasmacytoid dendritic cells derive exclusively from estrogen-resistant myeloid progenitors. Blood 108(3): 878, Feb 2006.
e3 Srivastava B, Quinn 3rd WJ, Hazard K, Erikson J, Allman D: Characterization of marginal zone B cell precursors. J Exp Med. 202(9): 1225-34, November 2005.
fc Allman D, Sambandam A, Kim S, Miller JP, Pagan A, Well D, Meraz A, Bhandoola A: Thymopoiesis independent of common lymphoid progenitors. Nat Immunol. 4(2): 168-174, February 2003.
ea Miller JP, Allman D: The decline in B lymphopoiesis in aged mice reflects loss of very early B-lineage precursors. J Immunol. 171(5): 2326-2330, September 2003.
130 Miller JP, Izon D, DeMuth W, Gerstein R, Bhandoola A, Allman D: The earliest step in B-lineage differentiation from common lymphoid progenitors is critically dependent upon interleukin-7. J Exp Med. 196(5): 705-711, September 2002.
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Selected Publications
f0 Harman BC, Northrup DL, Allman D: Resolution of unique Sca-1highc-Kit- lymphoid-biased progenitors in adult bone marrow. J Immunol. 181(11): 7514-7524, December 2008.18d Pongubala JM, Northrup DL, Lancki DW, Medina KL, Treiber T, Bertolino E, Thomas M, Grosschedl R, **Allman D, **Singh H : Transcription factor EBF restricts alternative lineage options and promotes B cell fate commitment independently of Pax5. Nature Immunol. 9(2): 203-215, February 2008 Notes: ** Shared senior authorship
10d Lindsley RC, Thomas M, Srivastava B, Allman D: Generation of peripheral B cells occurs via two spatially and temporally distinct pathways. Blood 109(6): 2521-8, March 2007 Notes: Epub 2006 Nov 14.
5d Thomas M, Calamito M, Srivastava B, Maillard I, 13 Pear WS, Allman D bb : Notch activity synergizes with B cell receptor and CD40 signaling to enhance B cell activation. Blood 109(8): 3342-50, April 2007 Notes: Epub 2006 Dec 19.
12d Allman D, Dalod M, Asselin-Paturel C, Delale T, Robbins SH, Trinchieri G, Biron CA, Kastner P, Chan S: Ikaros is required for plasmacytoid dendritic cell differentiation. Blood 108(13): 4025-34, Dec 2006 Notes: Epub 2006 Aug 15.
100 Harman BC, Miller JP, Nikbakht N, Gerstein R, Allman D: Mouse plasmacytoid dendritic cells derive exclusively from estrogen-resistant myeloid progenitors. Blood 108(3): 878, Feb 2006.
e3 Srivastava B, Quinn 3rd WJ, Hazard K, Erikson J, Allman D: Characterization of marginal zone B cell precursors. J Exp Med. 202(9): 1225-34, November 2005.
fc Allman D, Sambandam A, Kim S, Miller JP, Pagan A, Well D, Meraz A, Bhandoola A: Thymopoiesis independent of common lymphoid progenitors. Nat Immunol. 4(2): 168-174, February 2003.
ea Miller JP, Allman D: The decline in B lymphopoiesis in aged mice reflects loss of very early B-lineage precursors. J Immunol. 171(5): 2326-2330, September 2003.
130 Miller JP, Izon D, DeMuth W, Gerstein R, Bhandoola A, Allman D: The earliest step in B-lineage differentiation from common lymphoid progenitors is critically dependent upon interleukin-7. J Exp Med. 196(5): 705-711, September 2002.
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