Michael Paul Cancro, Ph.D.
3620 Hamilton Walk
Philadelphia, PA 19104
Lab: (215) 898-6668
University of Maryland College Park, 1973.
University of Maryland College Park, 1976.
University of Pennsylvania, 1977.
Description of Research ExpertiseResearch Interests
B lymphocyte development, selection, and homeostasis; immunobiology of aging.
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 PublicationsKnox JJ, Myles A, and Cancro MP: T-bet+ memory B cells: generation, function, and fate. Immunological Reviews. John Wiley & Sons, Ltd. 228(1): 149-160, January 2019.
Wang S , Wang J, Kumar V, Karnell J, Naiman B , Phillip S. Gross, Saifur Rahman, Kamelia Zerrouki, Hanna R, Morehouse C, Holoweckyj N, Liu H, Autoimmunity Mol Med Team, Manna, Z Goldbach-Mansky R, Wilson M, Hasni S, Siegel R, Sanjuan M, Streicher K, Cancro MP, Kolbeck, R and Ettinger, R: IL-21 drives expansion and plasma cell differentiation of autoreactive CD11chiT-bet+ B cells in SLE. Nature Communications 9: 1758, May 2018.
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 127(5): 1651-1663, 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.
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.
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.
Cancro MP: Signalling crosstalk in B cells: managing worth and need. Nat Rev Immunol. 9(9): 657-661, September 2009.
Miller JP, Stadanlick JE, Cancro MP: Space, selection, and surveillance: setting boundaries with BLyS. J. Immunol. 176(11): 6405-10, June 2006.
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.
Cancro MP: Peripheral B-cell maturation: the intersection of selection and homeostasis. Immunol Rev. Monroe JG, Koretzky G. (eds.). 197: 89-101, Feb 2004.