Michael Paul Cancro

faculty photo
Professor of Pathology and Laboratory Medicine
Department: Pathology and Laboratory Medicine
Graduate Group Affiliations

Contact information
284 John Morgan Building
3620 Hamilton Walk
Philadelphia, PA 19104
Office: (215) 898-8067
Fax: (215) 573-2350
Lab: (215) 898-6668
Education:
B.S. (Zoology)
University of Maryland College Park, 1973.
Ph.D. (Zoology/Genetics)
University of Maryland College Park, 1976.
Postdoc (Immunology)
University of Pennsylvania, 1977.
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Description of Research Expertise

Research Interests

B lymphocyte development, selection, and homeostasis; immunobiology of aging.

Research Summary

The size and makeup of mature B cell compartments is controlled by the proportion of immature B cells that complete differentiation, coupled with the average lifespan of mature B cells. Determining the selective and homeostatic factors controlling these parameters is thus key to understanding how the B cell repertoire is established and maintained. Our previous work defined the developmental stages spanning immature B cell formation in the marrow and final maturation in the periphery. More recently, we have focused on the molecular basis for survival and differentiation within these developmental subsets, with emphasis on the role of BLyS and BLyS receptors. Through developmental and kinetic studies in normal and mutant mice, we have found that BLyS controls peripheral B cell numbers in two ways: by varying the proportion of cells that complete transitional B cell development, and by serving as the primary determinant of mature follicular B cell lifespan. Ongoing studies are aimed at determining the molecular and cellular mechanism of BLyS activity in these subsets, as well as how BLyS responsiveness is integrated with BCR signaling. Additionally, we have begun studies of how these selective and homeostatic processes change with age. Our results indicate that the size and dynamics of most B cell subsets shift with age, suggesting age-associated alterations in both intrinsic and microenvironmental factors that govern these processes.

Selected Publications

Naradikian, MS, Hao, Y and Cancro MP: Age Associated B cells: Key mediators of both protective and autoreactive humoral responses Immunol. Rev. John Wiley & Sons, Ltd. 269(1): 118-129, January 2016 Notes: doi: 10.1111/imr.12380.

Sindhava, VJ, Oropallo, MA, Moody, K, Naradikian, M, Higdon, LE, Zhou, L, Myles, A, Green, N, Nündel, K, Stohl, W, Schmidt, AM, Cao, W Dorta-Estremera, S, Kambayashi, T Marshak-Rothstein, A, Cancro, MP: A TLR9-dependent checkpoint governs B cell responses to DNA-containing antigens J Clin Invest March 2017.

Naradikian, MS, Myles, A, Beiting, DP, Roberts, K, Dawson L, Herati, R, Bengsch, B, Linderman, S, Stelekati, E, Spolski, R, Wherry, EJ, Hunter, C, Hensley, S, Leonard, W, and Cancro MP: Cutting Edge: IL4, IL21, and IFNγ interact to govern TBET and CD11c expression in TLR-activated B cells. J. Immunol 197(4): 1023-1028, August 2016.

Russell Knode, LM, Naradikian,MS, Myles, A, Scholz, JL, Hao,Y, Liu,D, Ford,ML, Tobias J, Michael P. Cancro,MP , Gearhart, PA : Age-associated B cells express a diverse repertoire of VH and V genes with somatic hypermutation J Immunol 198: 1921-1927, February 2017 Notes: Prepublished 16 January 2017 doi: 10.4049/jimmunol.1601106.

Hao Y, O’Neill P, Naradikian MS, Scholz JL, Cancro MP : A B cell subset uniquely responsive to innate stimuli accumulates in aged mice. Blood 118(5): 1294-304, August 2011.

Cancro MP: The BLyS family of ligands and receptors: an archetype for niche-specific homeostatic regulation. Immunol Rev. Trinchieri, G. (eds.). 202: 237-249, December 2004.

Harless SM, Lentz VM, Sah AP, Hsu BL, Clise-Dwyer K, Hilbert DM, Hayes CE, Cancro MP: Competition for BLyS-mediated signaling through Bcmd/BR3 regulates peripheral B lymphocyte numbers. Curr Biol. 11(24): 1986-1989, December 2001.

Scholz JL, Cancro MP: Resolve, revise, and relax: The 3 Rs of B cell repertoire adjustment. Immunol Lett. 143(1): 2-8, March 2012.

Dosenovic P, Soldemo M, Scholz JL, O'Dell S, Grasset EK, Pelletier N, Karlsson MC, Mascola JR, Wyatt RT, Cancro MP, Karlsson Hedestam GB: BLyS-mediated modulation of naive B cell subsets impacts HIV Env-induced antibody responses. J Immunol. 188(12): 6018-26, June 2012.

Goenka R, Matthews AH, Zhang B, O’Neill PJ, Scholz JL, Migone T-S, Leonard WJ, Stohl W, Hershberg U, Cancro MP: Local BLyS production by T follicular cells mediates retention of high affinity B cells during affinity maturation J. Exp. Med. 211: 45-56, January 2014.

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Last updated: 07/17/2017
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