Isaac Harley, MD

Assistant Professor, Medicine-Rheumatology


FacultyPhoto
Medical School
  • MD, University of Cincinnati College of Medicine (2014)
Graduate Schools
  • MS, University of Oklahoma (2004)
  • PhD, University of Cincinnati (2014)
Undergraduate School
  • BS, University of Oklahoma (OK) (2004)
Internship
  • University of Colorado (2015)
Residency
  • University of Colorado, Internal Medicine (2017)
Fellowships
  • University of Colorado, Rheumatology (2020)
Languages
English
Department
Medicine-Rheumatology

Research Interests

– The etiology of Systemic Lupus Erythematosus – The application of genomics to improve care for rheumatic diseases – The genetics of systemic autoimmune and rheumatic diseases

Publications

  • Harley IT, Kaufman KM, Langefeld CD, Harley JB, Kelly JA. Genetic susceptibility to SLE: new insights from fine mapping and genome-wide association studies. Nat Rev Genet. 2009 May;10(5):285-90. PubMed PMID: 19337289
  • Harley IT, Niewold TB, Stormont RM, Kaufman KM, Glenn SB, Franek BS, Kelly JA, Kilpatrick JR, Hutchings D, Divers J, Bruner GR, Edberg JC, McGwin G Jr, Petri MA, Ramsey-Goldman R, Reveille JD, Vilá-Pérez LM, Merrill JT, Gilkeson GS, Vyse TJ, Alarcón-Riquelme ME, Cho SK, Jacob CO, Alarcón GS, Moser KL, Gaffney PM, Kimberly RP, Bae SC, Langefeld CD, Harley JB, Guthridge JM, James JA. The role of genetic variation near interferon-kappa in systemic lupus erythematosus. J Biomed Biotechnol. 2010;2010. PubMed PMID: 20706608
  • Harley IT, Stankiewicz TE, Giles DA, Softic S, Flick LM, Cappelletti M, Sheridan R, Xanthakos SA, Steinbrecher KA, Sartor RB, Kohli R, Karp CL, Divanovic S. IL-17 signaling accelerates the progression of nonalcoholic fatty liver disease in mice. Hepatology. 2014 May;59(5):1830-9. PubMed PMID: 24115079
  • Vaughn SE, Foley C, Lu X, Patel ZH, Zoller EE, Magnusen AF, Williams AH, Ziegler JT, Comeau ME, Marion MC, Glenn SB, Adler A, Shen N, Nath S, Stevens AM, Freedman BI, Tsao BP, Jacob CO, Kamen DL, Brown EE, Gilkeson GS, Alarcón GS, Reveille JD, Anaya JM, James JA, Moser KL, Criswell LA, Vilá LM, Alarcón-Riquelme ME, Petri M, Scofield RH, Kimberly RP, Ramsey-Goldman R, Binjoo Y, Choi J, Bae SC, Boackle SA, Vyse TJ, Guthridge JM, Namjou B, Gaffney PM, Langefeld CD, Kaufman KM, Kelly JA, Harley IT, Harley JB, Kottyan LC. Lupus risk variants in the PXK locus alter B-cell receptor internalization. Front Genet. 2014;5:450. PubMed PMID: 25620976
  • Harris VM, Koelsch KA, Kurien BT, Harley ITW, Wren JD, Harley JB, Scofield RH. Characterization of cxorf21 Provides Molecular Insight Into Female-Bias Immune Response in SLE Pathogenesis. Front Immunol. 2019;10:2160. PubMed PMID: 31695690
  • Chan CC, Harley ITW, Pfluger PT, Trompette A, Stankiewicz TE, Allen JL, Moreno-Fernandez ME, Damen MSMA, Oates JR, Alarcon PC, Doll JR, Flick MJ, Flick LM, Sanchez-Gurmaches J, Mukherjee R, Karns R, Helmrath M, Inge TH, Weisberg SP, Pamp SJ, Relman DA, Seeley RJ, Tschöp MH, Karp CL, Divanovic S. A BAFF/APRIL axis regulates obesogenic diet-driven weight gain. Nat Commun. 2021 May 18;12(1):2911. PubMed PMID: 34006859
  • Hou G, Harley ITW, Lu X, Zhou T, Xu N, Yao C, Qin Y, Ouyang Y, Ma J, Zhu X, Yu X, Xu H, Dai D, Ding H, Yin Z, Ye Z, Deng J, Zhou M, Tang Y, Namjou B, Guo Y, Weirauch MT, Kottyan LC, Harley JB, Shen N. SLE non-coding genetic risk variant determines the epigenetic dysfunction of an immune cell specific enhancer that controls disease-critical microRNA expression. Nat Commun. 2021 Jan 8;12(1):135. PubMed PMID: 33420081
  • Crute BW, Sheraden R, Ott VL, Harley ITW, Getahun A, Cambier JC. Inhibitory Receptor Trap: A Platform for Discovery of Inhibitory Receptors That Utilize Inositol Lipid and Phosphotyrosine Phosphatase Effectors. Front Immunol. 2020;11:592329. PubMed PMID: 33193438
  • Harris VM, Koelsch KA, Kurien BT, Harley ITW, Wren JD, Harley JB, Scofield RH. Characterization of cxorf21 Provides Molecular Insight Into Female-Bias Immune Response in SLE Pathogenesis. Front Immunol. 2019;10:2160. PubMed PMID: 31695690
  • Namjou B, Lingren T, Huang Y, Parameswaran S, Cobb BL, Stanaway IB, Connolly JJ, Mentch FD, Benoit B, Niu X, Wei WQ, Carroll RJ, Pacheco JA, Harley ITW, Divanovic S, Carrell DS, Larson EB, Carey DJ, Verma S, Ritchie MD, Gharavi AG, Murphy S, Williams MS, Crosslin DR, Jarvik GP, Kullo IJ, Hakonarson H, Li R, Xanthakos SA, Harley JB. GWAS and enrichment analyses of non-alcoholic fatty liver disease identify new trait-associated genes and pathways across eMERGE Network. BMC Med. 2019 Jul 17;17(1):135. PubMed PMID: 31311600
  • Harris VM, Harley ITW, Kurien BT, Koelsch KA, Scofield RH. Lysosomal pH Is Regulated in a Sex Dependent Manner in Immune Cells Expressing CXorf21 . Front Immunol. 2019;10:578. PubMed PMID: 31001245
  • Cappelletti M, Presicce P, Lawson MJ, Chaturvedi V, Stankiewicz TE, Vanoni S, Harley IT, McAlees JW, Giles DA, Moreno-Fernandez ME, Rueda CM, Senthamaraikannan P, Sun X, Karns R, Hoebe K, Janssen EM, Karp CL, Hildeman DA, Hogan SP, Kallapur SG, Chougnet CA, Way SS, Divanovic S. Type I interferons regulate susceptibility to inflammation-induced preterm birth. JCI Insight. 2017 Mar 9;2(5):e91288. PubMed PMID: 28289719
  • McAlees JW, Whitehead GS, Harley IT, Cappelletti M, Rewerts CL, Holdcroft AM, Divanovic S, Wills-Karp M, Finkelman FD, Karp CL, Cook DN. Distinct Tlr4-expressing cell compartments control neutrophilic and eosinophilic airway inflammation. Mucosal Immunol. 2015 Jul;8(4):863-73. PubMed PMID: 25465099
  • Vaughn SE, Foley C, Lu X, Patel ZH, Zoller EE, Magnusen AF, Williams AH, Ziegler JT, Comeau ME, Marion MC, Glenn SB, Adler A, Shen N, Nath S, Stevens AM, Freedman BI, Tsao BP, Jacob CO, Kamen DL, Brown EE, Gilkeson GS, Alarcón GS, Reveille JD, Anaya JM, James JA, Moser KL, Criswell LA, Vilá LM, Alarcón-Riquelme ME, Petri M, Scofield RH, Kimberly RP, Ramsey-Goldman R, Binjoo Y, Choi J, Bae SC, Boackle SA, Vyse TJ, Guthridge JM, Namjou B, Gaffney PM, Langefeld CD, Kaufman KM, Kelly JA, Harley IT, Harley JB, Kottyan LC. Lupus risk variants in the PXK locus alter B-cell receptor internalization. Front Genet. 2014;5:450. PubMed PMID: 25620976
  • Namjou B, Ni Y, Harley IT, Chepelev I, Cobb B, Kottyan LC, Gaffney PM, Guthridge JM, Kaufman K, Harley JB. The effect of inversion at 8p23 on BLK association with lupus in Caucasian population. PLoS One. 2014;9(12):e115614. PubMed PMID: 25545785
  • Harley IT, Stankiewicz TE, Giles DA, Softic S, Flick LM, Cappelletti M, Sheridan R, Xanthakos SA, Steinbrecher KA, Sartor RB, Kohli R, Karp CL, Divanovic S. IL-17 signaling accelerates the progression of nonalcoholic fatty liver disease in mice. Hepatology. 2014 May;59(5):1830-9. PubMed PMID: 24115079
  • Guthridge JM, Lu R, Sun H, Sun C, Wiley GB, Dominguez N, Macwana SR, Lessard CJ, Kim-Howard X, Cobb BL, Kaufman KM, Kelly JA, Langefeld CD, Adler AJ, Harley IT, Merrill JT, Gilkeson GS, Kamen DL, Niewold TB, Brown EE, Edberg JC, Petri MA, Ramsey-Goldman R, Reveille JD, Vilá LM, Kimberly RP, Freedman BI, Stevens AM, Boackle SA, Criswell LA, Vyse TJ, Behrens TW, Jacob CO, Alarcón-Riquelme ME, Sivils KL, Choi J, Joo YB, Bang SY, Lee HS, Bae SC, Shen N, Qian X, Tsao BP, Scofield RH, Harley JB, Webb CF, Wakeland EK, James JA, Nath SK, Graham RR, Gaffney PM. Two functional lupus-associated BLK promoter variants control cell-type- and developmental-stage-specific transcription. Am J Hum Genet. 2014 Apr 3;94(4):586-98. PubMed PMID: 24702955
  • Kurien BT, D'Sousa A, Bruner BF, Gross T, James JA, Targoff IN, Maier-Moore JS, Harley IT, Wang H, Scofield RH. Prolidase deficiency breaks tolerance to lupus-associated antigens. Int J Rheum Dis. 2013 Dec;16(6):674-80. PubMed PMID: 24330273
  • Harley IT, Giles DA, Pfluger PT, Burgess SL, Walters S, Hembree J, Raver C, Rewerts CL, Downey J, Flick LM, Stankiewicz TE, McAlees JW, Wills-Karp M, Balfour Sartor R, Divanovic S, Tschöp MH, Karp CL. Differential colonization with segmented filamentous bacteria and Lactobacillus murinus do not drive divergent development of diet-induced obesity in C57BL/6 mice. Mol Metab. 2013;2(3):171-83. PubMed PMID: 24049732
  • Harley IT, Karp CL. Obesity and the gut microbiome: Striving for causality. Mol Metab. 2012;1(1-2):21-31. PubMed PMID: 24024115
  • Namjou B, Choi CB, Harley IT, Alarcón-Riquelme ME, Kelly JA, Glenn SB, Ojwang JO, Adler A, Kim K, Gallant CJ, Boackle SA, Criswell LA, Kimberly RP, Brown EE, Edberg J, Alarcón GS, Stevens AM, Jacob CO, Gilkeson GS, Kamen DL, Tsao BP, Anaya JM, Kim EM, Park SY, Sung YK, Guthridge JM, Merrill JT, Petri M, Ramsey-Goldman R, Vilá LM, Niewold TB, Martin J, Pons-Estel BA, Vyse TJ, Freedman BI, Moser KL, Gaffney PM, Williams AH, Comeau ME, Reveille JD, Kang C, James JA, Scofield RH, Langefeld CD, Kaufman KM, Harley JB, Bae SC. Evaluation of TRAF6 in a large multiancestral lupus cohort. Arthritis Rheum. 2012 Jun;64(6):1960-9. PubMed PMID: 22231568
  • Schauberger EM, Ewart SL, Arshad SH, Huebner M, Karmaus W, Holloway JW, Friderici KH, Ziegler JT, Zhang H, Rose-Zerilli MJ, Barton SJ, Holgate ST, Kilpatrick JR, Harley JB, Lajoie-Kadoch S, Harley IT, Hamid Q, Kurukulaaratchy RJ, Seibold MA, Avila PC, Rodriguez-Cintrón W, Rodriguez-Santana JR, Hu D, Gignoux C, Romieu I, London SJ, Burchard EG, Langefeld CD, Wills-Karp M. Identification of ATPAF1 as a novel candidate gene for asthma in children. J Allergy Clin Immunol. 2011 Oct;128(4):753-760.e11. PubMed PMID: 21696813
  • Phillips CL, Gerbing R, Alonzo T, Perentesis JP, Harley IT, Meshinchi S, Bhatla D, Radloff G, Davies SM. MDM2 polymorphism increases susceptibility to childhood acute myeloid leukemia: a report from the Children's Oncology Group. Pediatr Blood Cancer. 2010 Aug;55(2):248-53. PubMed PMID: 20582981
  • Harley IT, Niewold TB, Stormont RM, Kaufman KM, Glenn SB, Franek BS, Kelly JA, Kilpatrick JR, Hutchings D, Divers J, Bruner GR, Edberg JC, McGwin G Jr, Petri MA, Ramsey-Goldman R, Reveille JD, Vilá-Pérez LM, Merrill JT, Gilkeson GS, Vyse TJ, Alarcón-Riquelme ME, Cho SK, Jacob CO, Alarcón GS, Moser KL, Gaffney PM, Kimberly RP, Bae SC, Langefeld CD, Harley JB, Guthridge JM, James JA. The role of genetic variation near interferon-kappa in systemic lupus erythematosus. J Biomed Biotechnol. 2010;2010. PubMed PMID: 20706608
  • Lu R, Vidal GS, Kelly JA, Delgado-Vega AM, Howard XK, Macwana SR, Dominguez N, Klein W, Burrell C, Harley IT, Kaufman KM, Bruner GR, Moser KL, Gaffney PM, Gilkeson GS, Wakeland EK, Li QZ, Langefeld CD, Marion MC, Divers J, Alarcón GS, Brown EE, Kimberly RP, Edberg JC, Ramsey-Goldman R, Reveille JD, McGwin G Jr, Vilá LM, Petri MA, Bae SC, Cho SK, Bang SY, Kim I, Choi CB, Martin J, Vyse TJ, Merrill JT, Harley JB, Alarcón-Riquelme ME, Nath SK, James JA, Guthridge JM. Genetic associations of LYN with systemic lupus erythematosus. Genes Immun. 2009 Jul;10(5):397-403. PubMed PMID: 19369946
  • Harley IT, Kaufman KM, Langefeld CD, Harley JB, Kelly JA. Genetic susceptibility to SLE: new insights from fine mapping and genome-wide association studies. Nat Rev Genet. 2009 May;10(5):285-90. PubMed PMID: 19337289
  • Gu Y, Harley IT, Henderson LB, Aronow BJ, Vietor I, Huber LA, Harley JB, Kilpatrick JR, Langefeld CD, Williams AH, Jegga AG, Chen J, Wills-Karp M, Arshad SH, Ewart SL, Thio CL, Flick LM, Filippi MD, Grimes HL, Drumm ML, Cutting GR, Knowles MR, Karp CL. Identification of IFRD1 as a modifier gene for cystic fibrosis lung disease. Nature. 2009 Apr 23;458(7241):1039-42. PubMed PMID: 19242412
  • Han S, Guthridge JM, Harley IT, Sestak AL, Kim-Howard X, Kaufman KM, Namjou B, Deshmukh H, Bruner G, Espinoza LR, Gilkeson GS, Harley JB, James JA, Nath SK. Osteopontin and systemic lupus erythematosus association: a probable gene-gender interaction. PLoS One. 2008 Mar 12;3(3):e0001757. PubMed PMID: 18335026
  • Harley JB, Harley IT, Guthridge JM, James JA. The curiously suspicious: a role for Epstein-Barr virus in lupus. Lupus. 2006;15(11):768-77. PubMed PMID: 17153849
  • Banach M, Harley ITW, McCarthy MK, Rester C, Stassinopoulos A, Kedl RM, Morrison TE, Cambier JC. Magnetic Enrichment of SARS-CoV-2 Antigen-Binding B Cells for Analysis of Transcriptome and Antibody Repertoire. Magnetochemistry. 2022; 8(2):23. https://doi.org/10.3390/magnetochemistry8020023
  • Systemic lupus erythematosus as a genetic disease. Harley ITW, Sawalha AH. Clin Immunol. 2022 Mar;236:108953. doi: 10.1016/j.clim.2022.108953. Epub 2022 Feb 9. PMID: 35149194 https://doi.org/10.1016/j.clim.2022.108953
  • Kaufman KM, Rankin J, Harley IT, Kelly JA, Harley JB, Scofield RH. A genetic marker within the CD44 gene confirms linkage at 11p13 in African-American families with lupus stratified by thrombocytopenia, but genetic association with CD44 is not present. Genes Immun. 2002 Oct;3 Suppl 1:S86-8. PubMed PMID: 12215908
  • Banach M, Harley ITW, Getahun A, Cambier JC. Comparative analysis of the repertoire of insulin-reactive B cells in type 1 diabetes-prone and resistant mice. Front Immunol. 2022;13:961209. PubMed PMID: 36275764
  • Harley ITW, Allison K, Scofield RH. Polygenic autoimmune disease risk alleles impacting B cell tolerance act in concert across shared molecular networks in mouse and in humans. Front Immunol. 2022;13:953439. PubMed PMID: 36090990
  • Harley ITW, Sawalha AH. Systemic lupus erythematosus as a genetic disease. Clin Immunol. 2022 Mar;236:108953. PubMed PMID: 35149194
  • Banach M, Harley IT, McCarthy MK, Rester C, Stassinopoulos A, Kedl RM, Morrison TE, Cambier JC. Magnetic Enrichment of SARS-CoV-2 Antigen-Binding B Cells for Analysis of Transcriptome and Antibody Repertoire. Magnetochemistry (Basel, Switzerland). 2022 February; 8(2):23. doi: 10.3390/magnetochemistry8020023.
  • Igoe A, Merjanah S, Harley ITW, Clark DH, Sun C, Kaufman KM, Harley JB, Kaelber DC, Scofield RH. Association between systemic lupus erythematosus and myasthenia gravis: A population-based National Study. Clin Immunol. 2023 Nov 8;:109810. [Epub ahead of print] PubMed PMID: 37949200
  • Chepelev I, Harley ITW, Harley JB. Modeling of horizontal pleiotropy identifies possible causal gene expression in systemic lupus erythematosus. Front Lupus. 2023;1. PubMed PMID: 37799268
  • Chau K, Raksadawan Y, Allison K, Ice JA, Scofield RH, Chepelev I, Harley ITW. Pervasive Sharing of Causal Genetic Risk Factors Contributes to Clinical and Molecular Overlap between Sjögren's Disease and Systemic Lupus Erythematosus. Int J Mol Sci. 2023 Sep 22;24(19). PubMed PMID: 37833897

Professional Memberships

  • American College of Rheumatology, Member

Practice Locations

UCHealth Rheumatology Clinic - Anschutz Medical Campus
1635 Aurora Ct
4th Floor
Aurora, CO 80045
720-848-7700

Hospital Affiliation
  • University of Colorado Hospital

Specialty Information

Specialties
  • Internal Medicine, Board Certification
  • Rheumatology, Board Certification
Conditions & Treatments
  • Immune System
  • Immune System - Autoimmune Disorders
Clinical Interests
- Systemic Lupus Erythematosus - Genetic Determinants of Autoimmune and Rheumatic Diseases

Care Philosophy
My goal is to provide excellent patient care. Doing so requires: 1) understanding each patient as a whole person – their goals, dreams and the challenges they face – and 2) forming a collaborative relationship so that we can work together to navigate diagnosis and treatment as it impacts their life.