Higgins, John, MD



Phone: 617-643-6129
Email: Higgins.John@mgh.harvard.edu
Lab: Higgins, John


  • Grune J, Lewis AJM, Yamazoe M, Hulsmans M, Rohde D, Xiao L, Zhang S, Ott C, Calcagno DM, Zhou Y, Timm K, Shanmuganathan M, Pulous FE, Schloss MJ, Foy BH, Capen D, Vinegoni C, Wojtkiewicz GR, Iwamoto I, Grune T, Brown D, Higgins J, Ferreira VM, Herring N, Channon KM, Neubauer S, Oxford Acute Myocardial Infarction (OxAMI) Study, Sosnovik DE, Milan DJ, Swirski FK, King KR, Aguirre AD, Ellinor PT, Nahrendorf M Neutrophils incite and macrophages avert electrical storm after myocardial infarction. Nat Cardiovasc Res. 2022;:ePub - DOI: 10.1038/s44161-022-00094-w

  • Truslow JG, Goto S, Homilius M, Mow C, Higgins JM, MacRae CA, Deo RC Cardiovascular Risk Assessment Using Artificial Intelligence-Enabled Event Adjudication and Hematologic Predictors. Circ Cardiovasc Qual Outcomes. 2022;15(6):e008007 - PMID: 35477255 - PMCID: PMC9208816 - DOI: 10.1161/CIRCOUTCOMES.121.008007

  • Schloss MJ, Hulsmans M, Rohde D, Lee IH, Severe N, Foy BH, Pulous FE, Zhang S, Kokkaliaris KD, Frodermann V, Courties G, Yang C, Iwamoto Y, Knudsen AS, McAlpine CS, Yamazoe M, Schmidt SP, Wojtkiewicz GR, Masson GS, Gustafsson K, Capen D, Brown D, Higgins JM, Scadden DT, Libby P, Swirski FK, Naxerova K, Nahrendorf M B lymphocyte-derived acetylcholine limits steady-state and emergency hematopoiesis. Nat Immunol. 2022;23(4):605-618 - PMID: 35352063 - PMCID: PMC8989652 - DOI: 10.1038/s41590-022-01165-7

  • Szafraniec HM, Valdez JM, Iffrig E, Lam WA, Higgins JM, Pearce P, Wood DK Feature tracking microfluidic analysis reveals differential roles of viscosity and friction in sickle cell blood. Lab Chip. 2022;22(8):1565-1575 - PMID: 35315465 - PMCID: PMC9004467 - DOI: 10.1039/d1lc01133b

  • Perazzo A, Peng Z, Young YN, Feng Z, Wood DK, Higgins JM, Stone HA The effect of rigid cells on blood viscosity: linking rheology and sickle cell anemia. Soft Matter. 2022;18(3):554-565 - PMID: 34931640 - PMCID: PMC8925304 - DOI: 10.1039/d1sm01299a

  • Geisness AC, Azul M, Williams D, Szafraniec H, De Souza DC, Higgins JM, Wood DK Ionophore-mediated swelling of erythrocytes as a therapeutic mechanism in sickle cell disease. Haematologica. 2021;107(6):1438-1447 - PMID: 34706495 - PMCID: PMC9152977 - DOI: 10.3324/haematol.2021.278666

  • Foy BH, Sundt T, Carlson JCT, Aguirre AD, Higgins JM White Blood Cell and Platelet Dynamics Define Human Inflammatory Recovery. medRxiv. 2021;:ePub - PMID: 34189534 - PMCID: PMC8240689 - DOI: 10.1101/2021.06.19.21259181

  • Demers M, Sturtevant S, Guertin KR, Gupta D, Desai K, Vieira BF, Li W, Hicks A, Ismail A, Gonçalves BP, Di Caprio G, Schonbrun E, Hansen S, Musayev FN, Safo MK, Wood DK, Higgins JM, Light DR MetAP2 inhibition modifies hemoglobin S to delay polymerization and improves blood flow in sickle cell disease. Blood Adv. 2021;5(5):1388-1402 - PMID: 33661300 - PMCID: PMC7948285 - DOI: 10.1182/bloodadvances.2020003670

  • Powe CE, James K, Higgins JM Response to Letter to the Editor from Marie Monlun: "Longitudinal changes in the relationship between Hemoglobin A1c and glucose tolerance across pregnancy and post-partum". J Clin Endocrinol Metab. 2021;106(1):e401-e402 - PMID: 32589732 - PMCID: PMC7765642 - DOI: 10.1210/clinem/dgaa402

  • Foy BH, Carlson JCT, Reinertsen E, Padros I Valls R, Pallares Lopez R, Palanques-Tost E, Mow C, Westover MB, Aguirre AD, Higgins JM Association of Red Blood Cell Distribution Width With Mortality Risk in Hospitalized Adults With SARS-CoV-2 Infection. JAMA Netw Open. 2020;3(9):e2022058 - PMID: 32965501 - PMCID: PMC7512057 - DOI: 10.1001/jamanetworkopen.2020.22058

  • Foy BH, Carlson JCT, Reinertsen E, Padros Valls R, Pallares Lopez R, Palanques-Tost E, Mow C, Westover MB, Aguirre AD, Higgins JM Elevated RDW is Associated with Increased Mortality Risk in COVID-19. medRxiv. 2020;:ePub - DOI: 10.1101/2020.05.05.20091702

  • Cremer S, Schloss MJ, Vinegoni C, Foy BH, Zhang S, Rohde D, Hulsmans M, Fumene Feruglio P, Schmidt S, Wojtkiewicz G, Higgins JM, Weissleder R, Swirski FK, Nahrendorf M Diminished Reactive Hematopoiesis and Cardiac Inflammation in a Mouse Model of Recurrent Myocardial Infarction. J Am Coll Cardiol. 2020;75(8):901-915 - PMID: 32130926 - PMCID: PMC7254576 - DOI: 10.1016/j.jacc.2019.12.056

  • Malka R, Brugnara C, Cialic R, Higgins JM Non-Parametric Combined Reference Regions and Prediction of Clinical Risk. Clin Chem. 2020;66(2):363-372 - PMID: 32040586 - PMCID: PMC7055670 - DOI: 10.1093/clinchem/hvz020

  • Edelson PK, James KE, Leong A, Arenas J, Cayford M, Callahan MJ, Bernstein SN, Tangren JS, Hivert MF, Higgins JM, Nathan DM, Powe CE Longitudinal Changes in the Relationship Between Hemoglobin A1c and Glucose Tolerance Across Pregnancy and Postpartum. J Clin Endocrinol Metab. 2020;105(5):ePub - PMID: 32010954 - PMCID: PMC7236626 - DOI: 10.1210/clinem/dgaa053

  • Foy BH, Gonçalves BP, Higgins JM Unraveling Disease Pathophysiology with Mathematical Modeling. Annu Rev Pathol. 2020;15:371-394 - PMID: 31977295 - DOI: 10.1146/annurev-pathmechdis-012419-032557

  • Foy BH, Li A, McClung J, Ranganath R, Higgins JM Data-driven physiologic thresholds for iron deficiency associated with hematologic decline. Am J Hematol. 2019;95(3):302-309 - PMID: 31849101 - DOI: 10.1002/ajh.25706

  • Chaudhury A, Miller GD, Eichner D, Higgins JM Single-cell modeling of routine clinical blood tests reveals transient dynamics of human response to blood loss. eLife. 2019;8:ePub - PMID: 31845889 - PMCID: PMC6917488 - DOI: 10.7554/eLife.48590

  • Valdez JM, Datta YH, Higgins JM, Wood DK A microfluidic platform for simultaneous quantification of oxygen-dependent viscosity and shear thinning in sickle cell blood. APL Bioeng. 2019;3(4):046102 - PMID: 31803859 - PMCID: PMC6881198 - DOI: 10.1063/1.5118212

  • Di Caprio G*, Schonbrun E*, Gonçalves BP, Valdez JM, Wood DK, Higgins JM High-throughput assessment of hemoglobin polymer in single red blood cells from sickle cell patients under controlled oxygen tension. Proc Natl Acad Sci U S A. 2019;116(50):25236-25242 - PMID: 31767751 - PMCID: PMC6911208 - DOI: 10.1073/pnas.1914056116

  • Larkin M, Nathan DM, Bebu I, Krause-Steinrauf H, Herman WH, Higgins JM, Tiktin M, Cohen RM, Lund C, Bergenstal RM, Johnson M, Arends V, Research Group G Rationale and Design for a GRADE Substudy of Continuous Glucose Monitoring. Diabetes Technol Ther. 2019;21(12):682-690 - PMID: 31393176 - PMCID: PMC7207016 - DOI: 10.1089/dia.2019.0202

  • Cohen RM, Franco RS, Smith EP, Higgins JM When the A1c and the blood glucose don't match: how much is determined by race, by genetics, by differences in mean red blood cell age?. J Clin Endocrinol Metab. 2019;104(3):707-710 - PMID: 30445523 - DOI: 10.1210/jc.2018-02409

  • Lu X, Chaudhury A, Higgins JM, Wood DK Oxygen-dependent flow of sickle trait blood as an in vitro therapeutic benchmark for sickle cell disease treatments. Am J Hematol. 2018;93(10):1227-1235 - PMID: 30033564 - PMCID: PMC6604607 - DOI: 10.1002/ajh.25227

  • Chaudhury A, Noiret L, Higgins JM White blood cell population dynamics for risk stratification of acute coronary syndrome. Proc Natl Acad Sci U S A. 2017;114(46):12344-12349 - PMID: 29087321 - PMCID: PMC5699055 - DOI: 10.1073/pnas.1709228114

  • Noiret L, Slater A, Higgins JM Determinants of red blood cell alloantibody detection duration: analysis of multiply alloimmunized patients supports peritransfusion factors. Transfusion. 2017;57(8):1930-1937 - PMID: 28639314 - DOI: 10.1111/trf.14157

  • Lu X, Galarneau MM, Higgins JM, Wood DK A microfluidic platform to study the effects of vascular architecture and oxygen gradients on sickle blood flow. Microcirculation. 2017;24(5):ePub - PMID: 28129479 - PMCID: PMC5505799 - DOI: 10.1111/micc.12357

  • Malka R, Nathan DM, Higgins JM Mechanistic modeling of hemoglobin glycation and red blood cell kinetics enables personalized diabetes monitoring. Sci Transl Med. 2016;8:359ra130 - PMID: 27708063 - PMCID: PMC5714656 - DOI: 10.1126/scitranslmed.aaf9304

  • Hosseini P, Abidi SZ, Du E, Papageorgiou DP, Choi Y, Park Y, Higgins JM, Kato GJ, Suresh S, Dao M, Yaqoob Z, So PT Cellular normoxic biophysical markers of hydroxyurea treatment in sickle cell disease. Proc Natl Acad Sci U S A. 2016;113(34):9527-32 - PMID: 27512047 - PMCID: PMC5003247 - DOI: 10.1073/pnas.1610435113

  • Lu X, Wood DK, Higgins JM Deoxygenation Reduces Sickle Cell Blood Flow at Arterial Oxygen Tension. Biophys J. 2016;110(12):2751-8 - PMID: 27332133 - PMCID: PMC4919586 - DOI: 10.1016/j.bpj.2016.04.050

  • Huck A, Pozdnyakova O, Brunner A, Higgins JM, Fathi AT, Hasserjian RP Prior cytopenia predicts worse clinical outcome in acute myeloid leukemia. Leuk Res. 2015;39(10):1034-40 - PMID: 26220865 - PMCID: PMC5764101 - DOI: 10.1016/j.leukres.2015.06.012

  • Di Caprio G, Stokes C, Higgins JM, Schonbrun E Single-cell measurement of red blood cell oxygen affinity. Proc Natl Acad Sci U S A. 2015;112(32):9984-9 - PMID: 26216973 - PMCID: PMC4538663 - DOI: 10.1073/pnas.1509252112

  • Patel H, Patel H, Higgins JM Modulation of Red Blood Cell Population Dynamics is a Fundamental Homeostatic Response to Disease. Am J Hematol. 2015;90(5):422-8 - PMID: 25691355 - PMCID: PMC4717489 - DOI: 10.1002/ajh.23982

  • Higgins JM Red Blood Cell Population Dynamics. Clin Lab Med. 2014;35(1):43-57 - PMID: 25676371 - PMCID: PMC4717490 - DOI: 10.1016/j.cll.2014.10.002

  • Jaiswal S, Fontanillas P, Flannick J, Manning A, Grauman PV, Mar BG, Lindsley RC, Mermel CH, Burtt N, Chavez A, Higgins JM, Moltchanov V, Kuo FC, Kluk MJ, Henderson B, Kinnunen L, Koistinen HA, Ladenvall C, Getz G, Correa A, Banahan BF, Gabriel S, Kathiresan S, Stringham HM, McCarthy MI, Boehnke M, Tuomilehto J, Haiman C, Groop L, Atzmon G, Wilson JG, Neuberg D, Altshuler D, Ebert BL Age-Related Clonal Hematopoiesis Associated with Adverse Outcomes. N Engl J Med. 2014;371(26):2488-2498 - PMID: 25426837 - PMCID: PMC4306669 - DOI: 10.1056/NEJMoa1408617

  • Malka R, Delgado FF, Manalis SR, Higgins JM In Vivo Volume and Hemoglobin Dynamics of Human Red Blood Cells. PLoS Comput Biol. 2014;10(10):e1003839 - PMID: 25299941 - PMCID: PMC4191880 - DOI: 10.1371/journal.pcbi.1003839

  • Louis DN, Gerber GK, Baron JM, Bry L, Dighe AS, Getz G, Higgins JM, Kuo FC, Lane WJ, Michaelson JS, Le LP, Mermel CH, Gilbertson JR, Golden JA Computational pathology: an emerging definition. Arch Pathol Lab Med. 2014;138(9):1133-8 - PMID: 25171694 - DOI: 10.5858/arpa.2014-0034-ED

  • Archer NM, Shmukler BE, Andolfo I, Vandorpe DH, Gnanasambandam R, Higgins JM, Rivera A, Fleming MD, Sachs F, Gottlieb PA, Iolascon A, Brugnara C, Alper SL, Nathan DG Hereditary xerocytosis revisited. Am J Hematol. 2014;89(12):1142-1146 - PMID: 25044010 - PMCID: PMC4237618 - DOI: 10.1002/ajh.23799

  • Baron JM, Dighe AS, Arnaout R, Balis UJ, Black-Schaffer WS, Carter AB, Henricks WH, Higgins JM, Jackson BR, Kim J, Klepeis VE, Le LP, Louis DN, Mandelker D, Mermel CH, Michaelson JS, Nagarajan R, Platt ME, Quinn AM, Rao L, Shirts BH, Gilbertson JR The 2013 symposium on pathology data integration and clinical decision support and the current state of field. J Pathol Inform. 2014;5:2 - PMID: 24672737 - PMCID: PMC3952400 - DOI: 10.4103/2153-3539.126145

  • Schonbrun E, Malka R, Di Caprio G, Schaak D, Higgins JM Quantitative absorption cytometry for measuring red blood cell hemoglobin mass and volume. Cytometry A. 2014;85(4):332-8 - PMID: 24677669 - PMCID: PMC4717472 - DOI: 10.1002/cyto.a.22450

  • Golub MS, Hogrefe CE, Malka R, Higgins JM Developmental Plasticity of red blood cell homeostasis. Am J Hematol. 2014;89(5):459-66 - PMID: 24415575 - PMCID: PMC4086753 - DOI: 10.1002/ajh.23666

  • Feijó Delgado F, Cermak N, Hecht VC, Son S, Li Y, Knudsen SM, Olcum S, Higgins JM, Chen J, Grover WH, Manalis SR Intracellular Water Exchange for Measuring the Dry Mass, Water Mass and Changes in Chemical Composition of Living Cells. PLoS ONE. 2013;8(7):e67590 - PMID: 23844039 - PMCID: PMC3699654 - DOI: 10.1371/journal.pone.0067590

  • Byun H, Hillman TR, Higgins JM, Diez-Silva M, Peng Z, Dao M, Dasari RR, Suresh S, Park Y Optical measurement of biomechanical properties of individual erythrocytes from a sickle cell patient. Acta Biomater. 2012;8(11):4130-8 - PMID: 22820310 - PMCID: PMC3576574 - DOI: 10.1016/j.actbio.2012.07.011

  • Kim Y, Higgins JM, Dasari RR, Suresh S, Park Y Anisotropic light scattering of individual sickle red blood cells. J Biomed Opt. 2012;17(4):040501 - PMID: 22559667 - PMCID: PMC3602817 - DOI: 10.1117/1.JBO.17.4.040501

  • Wood DK, Soriano A, Mahadevan L, Higgins JM, Bhatia SN A Biophysical Indicator of Vaso-occlusive Risk in Sickle Cell Disease. Sci Transl Med. 2012;4(123):123ra26 - PMID: 22378926 - PMCID: PMC3633235 - DOI: 10.1126/scitranslmed.3002738

  • Leuschner F, Rauch PJ, Ueno T, Gorbatov R, Marinelli B, Lee WW, Dutta P, Wei Y, Robbins C, Iwamoto Y, Sena B, Chudnovskiy A, Panizzi P, Keliher E, Higgins JM, Libby P, Moskowitz MA, Pittet MJ, Swirski FK, Weissleder R, Nahrendorf M Rapid monocyte kinetics in acute myocardial infarction are sustained by extramedullary monocytopoiesis. J Exp Med. 2012;209(1):123-37 - PMID: 22213805 - PMCID: PMC3260875 - DOI: 10.1084/jem.20111009

  • Baron JM, Higgins JM, Dzik WH A Revised Timeline for the Origin of Plasmodium falciparum as a Human Pathogen. J Mol Evol. 2011;73(5-6):297-304 - PMID: 22183792 - DOI: 10.1007/s00239-011-9476-x

  • Grover WH, Bryan AK, Diez-Silva M, Suresh S, Higgins JM, Manalis SR Measuring single-cell density. Proc Natl Acad Sci U S A. 2011;108(27):10992-10996 - PMID: 21690360 - PMCID: PMC3131325 - DOI: 10.1073/pnas.1104651108

  • Higgins JM, Mahadevan L Physiological and pathological population dynamics of circulating human red blood cells. Proc Natl Acad Sci U S A. 2010;107(47):20587-92 - PMID: 21059904 - PMCID: PMC2996693 - DOI: 10.1073/pnas.1012747107

  • Higgins JM, Sloan SR Response: Other factors may contribute to differences between sickle cell and non-sickle cell patients. Blood. 2010;115(21):4315-6 - PMID: 20508172

  • Setoguchi S, Higgins JM, Mogun H, Mootha VK, Avorn J Propranolol and the risk of hospitalized myopathy: Translating chemical genomics findings into population-level hypotheses. Am Heart J. 2010;159(3):428-433 - PMID: 20211305 - DOI: 10.1016/j.ahj.2009.12.008

  • Higgins JM, Eddington DT, Bhatia SN, Mahadevan L Statistical dynamics of flowing red blood cells by morphological image processing. PLoS Comput Biol. 2009;5(2):e1000288 - PMID: 19214200 - PMCID: PMC2631282 - DOI: 10.1371/journal.pcbi.1000288

  • Higgins JM, Sloan SR Stochastic modeling of human RBC alloimmunization: evidence for a distinct population of immunologic responders. Blood. 2008;112(6):2546-53 - PMID: 18535200 - DOI: 10.1182/blood-2008-03-146415

  • Higgins JM, Eddington DT, Bhatia SN, Mahadevan L Sickle cell vasoocclusion and rescue in a microfluidic device. Proc Natl Acad Sci U S A. 2007;104(51):20496-500 - PMID: 18077341 - PMCID: PMC2154459 - DOI: 10.1073/pnas.0707122105

  • Sabeti PC, Reich DE, Higgins JM, Levine HZ, Richter DJ, Schaffner SF, Gabriel SB, Platko JV, Patterson NJ, McDonald GJ, Ackerman HC, Campbell SJ, Altshuler D, Cooper R, Kwiatkowski D, Ward R, Lander ES Detecting recent positive selection in the human genome from haplotype structure. Nature. 2002;419(6909):832-7 - PMID: 12397357 - DOI: 10.1038/nature01140

  • Reich DE, Schaffner SF, Daly MJ, McVean G, Mullikin JC, Higgins JM, Richter DJ, Lander ES, Altshuler D Human genome sequence variation and the influence of gene history, mutation and recombination. Nat Genet. 2002;32(1):135-42 - PMID: 12161752 - DOI: 10.1038/ng947

  • Gabriel SB, Schaffner SF, Nguyen H, Moore JM, Roy J, Blumenstiel B, Higgins J, DeFelice M, Lochner A, Faggart M, Liu-Cordero SN, Rotimi C, Adeyemo A, Cooper R, Ward R, Lander ES, Daly MJ, Altshuler D The structure of haplotype blocks in the human genome. Science. 2002;296(5576):2225-9 - PMID: 12029063 - DOI: 10.1126/science.1069424

  • Sachidanandam R, Weissman D, Schmidt SC, Kakol JM, Stein LD, Marth G, Sherry S, Mullikin JC, Mortimore BJ, Willey DL, Hunt SE, Cole CG, Coggill PC, Rice CM, Ning Z, Rogers J, Bentley DR, Kwok PY, Mardis ER, Yeh RT, Schultz B, Cook L, Davenport R, Dante M, Fulton L, Hillier L, Waterston RH, McPherson JD, Gilman B, Schaffner S, Van Etten WJ, Reich D, Higgins J, Daly MJ, Blumenstiel B, Baldwin J, Stange-Thomann N, Zody MC, Linton L, Lander ES, Altshuler D, A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms. Nature. 2001;409(6822):928-33 - PMID: 11237013 - DOI: 10.1038/35057149