PEOPLE

Michael Paul Cancro, PhD

Professor of Pathology and Laboratory Medicine
Perelman School of Medicine at the University of Pennsylvania 

Vice Chair for Faculty Development & Academic Affairs
Department of Pathology and Laboratory Medicine

Contact InformationPerelman School of Medicine at the University of Pennsylvania
Department of Pathology and Laboratory Medicine
John Morgan Building, Rm 284
3620 Hamilton Walk
Philadelphia, PA 19104
Tel: 215-898-8067
Email: cancro@pennmedicine.upenn.edu

Specialty Division

Cancer and Immunobiology

Research Expertise

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

Research Summary:
The Cancro laboratory studies B lymphocyte development, homeostasis and activation. Early work from our lab defined the transitional B cell subset; a developmental stage spanning immature B cell formation in the bone marrow and final maturation in the periphery. In addition, we have made key conceptual and mechanistic contributions towards understanding how the cytokine BLyS (a.k.a. BAFF) and its receptors control peripheral B cell selection and numbers. Most recently, we have focused on our recent discovery of a novel B cell subset that enlarges continuously with age, termed Age Associated B cells (ABCs). Our ongoing studies have revealed that this subset is characterized by the expression of the transcriptional regulator Tbet, and includes a spleen resident memory B cell pool that is key to anti-microbial immunity, but that is also expanded in several autoimmune diseases. Current work is thus aimed at understanding the origins of ABCs, as well as their roles in both protective immunity and autoimmune disease.

Itmat Expertise

B lymphocyte development; B lymphocyte activation; B lymphocyte tolerance; immune memory; autoimmunity; SLE

Graduate Groups

Immunology

Education

BS (Zoology), University of Maryland College Park, 1973 
PhD (Zoology/Genetics), University of Maryland College Park, 1976

Specialty Certification

Postgraduate Training

Postdoctoral Fellow, Immunology, University of Pennsylvania, 1976-78

Awards and Honors

AAI Junior Investigator Travel Award, 1980
Berwick Award for Medical Teaching, 1984
Masters of Arts (Honorary), University of Pennsylvania, 1984
Research Career Development Award (K04, NIAID), 1985-89
Lindback Award for Distinguished Teaching, 1986
Louis R. Dinon Teaching Award, 1987
Distinguished Basic Science Educator Award, 1989
Louis R. Dinon Teaching Award (2nd receipt), 1990
Peter C. Nowell Teaching Award, 1990
Elected Member, Henry Kunkel Society, 2006
Elected Member, John Morgan Society, 2010
Simon Flexner Award for Graduate Student Education, University of Pennsylvania, 2011
Lady Barbara Colyton Prize for Autoimmunity Research, 2012
Batsheva de Rothschild Visiting Professorship, 2012
Distinguished Service Award, Department of Pathology and Laboratory Medicine, 2019
Distinguished Fellow, American Association of Immunologists, 2020
American Association of Immunologists Distinguished Lectureship, 2021

Memberships and Professional Organizations

Immunology Graduate Group (IGG), University of Pennsylvania, 1978-present
--- Admissions Committee, 1979-84, 2000-present
--- Student Affairs Committee, 1979-91, 2003-10 (Co-Chairperson), 2011-present
--- Chair, IGG, 1986-89, 2000-03 (second term)
--- Executive Committee, 2004-present
International Society for Developmental and Comparative Immunology, 1978-present
American Association of Immunologists, 1978-present
--- Education Committee, 1988-92
--- Publications Committee, 2004-07
Allergy and Immunology (now CMI-A) Study Section, Ad Hoc Panel Member, 1984-2000
Immunological Sciences (IMS, now TTT) Study Section, Review Panel Member, 1985-88
University of Pennsylvania School of Medicine, Teaching Awards Committee, 1985-97 (Chairperson, 1988-97)
Immunobiology (IMB, now CMI-B) Study Section, Ad Hoc Panel Member, 1990-2010
University of Pennsylvania School of Medicine, Curriculum Committee, 1990-97 (Chairperson, 1992, 1994, 1996)
ZRG SSS-4 Special Emphasis Study Section, Member/Chairperson, 1990-2000
Liaison Committee on Medical Education (Accrediting body of AAMC), Faculty Fellow, 1992-93
AIDS Special Study Section, Panel Member, 1996-98
Henry Kunkel Society, 2000-present (Council Member, 2012-15)
USAMRMC Breast Cancer Cell Biology Study Section 3, 2002-04 (Chairperson, 2004)
University of Virginia School of Medicine, Training Program in Immunology (T32), Advisory Panel, 2004-10
NIH/NIAID:
--- F07 Study Section, Chairperson, 2005-08
--- Cooperative Centers for Translational Research on Human Immunology and Biodefense, Review Panel, 2008
--- Autoimmune Centers of Excellence, Member/Reviewer, 2009
--- Protection of Human Health Immunology and Vaccines (ZAI1 QV-I Study Section), Review Panel, 2010
--- Special Emphasis Review Panel (ZAI1-DR-A-M2), 2012
--- Special Emphasis Review Panel (ZAI1-PA-I J1) Autoimmune Centers of Excellence, Chairperson, 2013
--- Special Emphasis Review Panel (ZAI1-LAR-I-J1) Cooperative Centers on Human Immunology, Chairperson, 2013, 2018
--- Special Panel (ZRG1 IMM-H_02) “Immune Mechanisms,” Chairperson, 2015
--- Special Section (ZAI1-AWS-M-S1) Autoimmune Responses, Review Panel, 2016
--- ZAI1 NVM-I (J1) 1, Immunity in neonates and infants (U01) Review Panel, 2016
--- Special Panel (ZAI1-PA-I-S1) Human Immune Profiling Consortium Program, Chair, 2016, 2021
--- ZAI1 AZ-M (J1) Support for Conferences & Scientific Meetings (R13), Review Panel, 2017
--- Special Emphasis Panel for RFA AI 17-037 Immunity in the Elderly Clinical Trial Optional, Chairperson, 2018
--- Neonatal Immunity Special Emphasis Review Panel, Chairperson, 2019
--- New Innovators Award (DP2) Review Panel, Chairperson, 2020-23
--- Emergency Awards Rapid Investigation of SARS-CoV-2 & COVID-19 Special Emphasis Panel, Chair, June/Aug, 2020
--- Human Immune Profiling Consortium (HPC) Program Review Panel, Chairperson, 2021
--- Immune Development in Early Life (IDEAL) Program Review Panel, Chairperson, 2021
Trudeau Institute, Program in the Immunology of Aging, Advisory Panel, Co-Chair, 2006-12
Lupus Research Alliance, Reviewer, 2006-present
Aging Systems and Geriatrics (ASG) Study Section, Member, Ad Hoc, 2008-18
Alliance for Lupus Research Target Identification in Lupus (TIL) Review Panel, 2008
Arthritis Foundation Research Grant Program, Review Panel Team Leader, 2009-11
Faculty of 1000, Lymphocyte Development Section Member, 2010-present
College of CSR Reviewers (NIH), 2010-present
NIH/NIAID/DAIDS, ZAI1-NVM-I-M Program Initiatives in HIV Broadly Neutralizing Antibodies, Review Panel, Chair, 2012
Multiple Sclerosis Society Fast-Forward Grant Program Review Panel, 2012
NIH/NIA/NIAIA, ZAI1-LAR-I B cells in Healthy Aging, Review Panel, Chairperson, 2013
FDA, Division of Biologicals Scientific Advisory and Review Panel, 2014
University of Connecticut Health Sciences Center, Immunology of Aging Program, Advisory Panel, Co-Chair, 2014-19
Glaxo Smith-Kline
--- Expert Advisory Panel on B cell therapeutics (Frankfurt, Germany), 2014
--- Expert Panel on combination therapies in autoimmunity (London, UK), 2018
Rheumafonds (Dutch Arthritis Foundation); Netherlands Basic Research Program, Invited Reviewer, 2016
University of Alabama Birmingham School of Medicine
--- Depts. Of Microbiology & Immunology, U19 Program in Infectious Disease Immunology, Advisory Board, 2016-21
--- T32 Training Programs in Immunology, Microbiology, & Rheumatology, Advisory Board, 2016-21
NIH/NIGMS
--- ZGM1 TWD-Y (KR) NIH Pathway to Independence Award K99/R00 Applications, Review Panel, Chair, 2017
--- ZGM1 TWD-8 (KR) NIH Pathway to Independence Award K99/R00 Applications, Review Panel, Chair, 2018
--- ZGM1 (KR), ZGM1 TWD-9 (KR) NIH Pathway to Independence Award K99/R00 Applications, Review Panel, Chair, 2019
--- Pathway to Independence Award K99/R00 Applications, Review Panel, Chair, 2021
NIH/CSR
--- AARR (AIDS-Related Research) Special Emphasis Panel ZRG1 AARR-P (03), 2018
--- Aging Systems & Geriatrics Study Section, Reviewer, 2019
--- ZRG1 BDCN A (50) R Brain Disorders and Clinical Neuroscience Panel, 2019
--- ZRG1 BDCN B (55) Juvenile Protective Factors and Their Effects on Aging Review Panel, Acting Chair, 2020
--- ZRG1 BDCN-B (55) Dynamic Interactions Between Systemic or Non-Neuronal Systems & the Brain in Aging & in Alzheimer’s Disease, Review Panel, 2018
CDMRP, DOD Lupus Research Program Impact Award Review Panel, 2019
Austrian Research Foundation, Excellence in Vaccine Development Program, Expert Reviewer, 2021, 2023
Lupus Research Alliance Global Team Science Award Review Panel, 2021
NIH/NIDD, Pathway to Independence Award (K99/R00) Review Panel, 2021
Swiss National Science Foundation, Expert Reviewer, 2022-23
Medical Research Council, Late Investments Program, External Expert Reviewer, 2022
Versus Arthritis (UK), Fellowship Expert Group Reviewer, 2023-present

Web Links


Selected Publications

Partial RAG deficiency in humans induces dysregulated peripheral lymphocyte development and humoral tolerance defect with accumulation of T-bet+ B cells

Csomos K, Ujhazi B, Blazso P, Herrera JL, Tipton CM, Kawai T, Gordon S, Ellison M, Wu K, Stowell M, Haynes L, Cruz R, Zakota B, Nguyen J, Altrich M, Geier CB, Sharapova S, Dasso JF, Leiding JW, Smith G, Al-Herz W, de Barros Dorna M, Fadugba O, Fronkova E, Kanderova V, Svaton M, Henrickson SE, Hernandez JD, Kuijpers T, Kandilarova SM, Naumova E, Milota T, Sediva A, Moshous D, Neven B, Saco T, Sargur R, Savic S, Sleasman J, Sunkersett G, Ward BR, Komatsu M, Pittaluga S, Kumanovics A, Butte MJ, Cancro MP, Pillai S, Meffre E, Notarangelo LD, Walter JE. Nat Immunol 23(8):1256-1272, Aug 2022. doi: 10.1038/s41590-022-01271-6. Epub 2022 Jul 28. PMID: 35902638; PMCID: PMC9355881.

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Lipid nanoparticles enhance the efficacy of mRNA and protein subunit vaccines by inducing robust T follicular helper cell and humoral responses

Alameh MG, Tombácz I, Bettini E, Lederer K, Sittplangkoon C, Wilmore JR, Gaudette BT, Soliman OY, Pine M, Hicks P, Manzoni TB, Knox JJ, Johnson JL, Laczkó D, Muramatsu H, Davis B, Meng W, Rosenfeld AM, Strohmeier S, Lin PJC, Mui BL, Tam YK, Karikó K, Jacquet A, Krammer F, Bates P, Cancro MP, Weissman D, Luning Prak ET, Allman D, Locci M, Pardi N. Immunity 54(12):2877-2892.e7, Dec 2021. doi: 10.1016/j.immuni.2021.11.001. Epub 2021 Nov 4. Erratum in: Immunity. 2022 Jun 14;55(6):1136-1138. PMID: 34852217; PMCID: PMC8566475.

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Trivalent nucleoside-modified mRNA vaccine yields durable memory B cell protection against genital herpes in preclinical models

Awasthi S, Knox JJ, Desmond A, Alameh MG, Gaudette BT, Lubinski JM, Naughton A, Hook LM, Egan KP, Tam YK, Pardi N, Allman D, Luning Prak ET, Cancro MP, Weissman D, Cohen GH, Friedman HM. J Clin Invest 131(23):e152310, Dec 2021. doi: 10.1172/JCI152310. PMID: 34618692; PMCID: PMC8631595.

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Lymph node formation and B cell homeostasis require IKK-α in distinct endothelial cell-derived compartments

McCorkell KA, Jayachandran N, Cully MD, Freund-Brown J, Weinkopff T, Monslow J, Hu Y, Puré E, Freedman BD, Alvarez JI, Cancro MP, May MJ. Proc Natl Acad Sci U S A 118(48):e2100195118, Nov 2021. doi: 10.1073/pnas.2100195118. PMID: 34810256; PMCID: PMC8640927.

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The dynamic epigenetic regulation of the inactive X chromosome in healthy human B cells is dysregulated in lupus patients

Pyfrom S, Paneru B, Knox JJ, Cancro MP, Posso S, Buckner JH, Anguera MC. Proc Natl Acad Sci U S A 118(24):e2024624118, Jun 2021. doi: 10.1073/pnas.2024624118. PMID: 34103397; PMCID: PMC8214693. 

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The Transcription Factor T-bet Resolves Memory B Cell Subsets with Distinct Tissue Distributions and Antibody Specificities in Mice and Humans

Johnson JL, Rosenthal RL, Knox JJ, Myles A, Naradikian MS, Madej J, Kostiv M, Rosenfeld AM, Meng W, Christensen SR, Hensley SE, Yewdell J, Canaday DH, Zhu J, McDermott AB, Dori Y, Itkin M, Wherry EJ, Pardi N, Weissman D, Naji A, Prak ETL, Betts MR, Cancro MPImmunity 52(5):842-855.e6, May 2020. doi: 10.1016/j.immuni.2020.03.020. Epub 2020 Apr 29. PMID: 32353250; PMCID: PMC7242168.

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BCR-Induced Ca2+ Signals Dynamically Tune Survival, Metabolic Reprogramming, and Proliferation of Naive B Cells

Berry CT, Liu X, Myles A, Nandi S, Chen YH, Hershberg U, Brodsky IE, Cancro MP, Lengner CJ, May MJ, Freedman BD. Cell Rep 31(2):107474, Apr 2020. doi: 10.1016/j.celrep.2020.03.038. PMID: 32294437; PMCID: PMC7301411.

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Age-Associated B Cells

Cancro MPAnnu Rev Immunol 38:315-340, Apr 2020. doi: 10.1146/annurev-immunol-092419-031130. Epub 2020 Jan 27. PMID: 31986068.

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Ancient BCMA-like Genes Herald B Cell Regulation in Lampreys

Das S, Sutoh Y, Cancro MP, Rast JP, Han Q, Bommakanti G, Cooper MD, Hirano M. J Immunol 203(11):2909-2916, Dec 2019. doi: 10.4049/jimmunol.1900026. Epub 2019 Oct 30. PMID: 31666307; PMCID: PMC6864319.

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Nucleoside-modified mRNA encoding HSV-2 glycoproteins C, D, and E prevents clinical and subclinical genital herpes

Awasthi S, Hook LM, Pardi N, Wang F, Myles A, Cancro MP, Cohen GH, Weissman D, Friedman HM. Sci Immunol 4(39):eaaw7083, Sep 2019. doi: 10.1126/sciimmunol.aaw7083. PMID: 31541030; PMCID: PMC6822172.

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