Gyungah Jun PhD
Associate Professor, Biomedical Genetics
Assistant Professor, Ophthalmology
72 East Concord Street | (617) 842-7998
Evans Center for Interdisciplinary Biomedical Research
Dr. Jun is a globally renowned Alzheimer’s disease (AD) geneticist and an expert in analysis of “big data”. Her innovative contributions to the Alzheimer’s Disease Genetics Consortium (ADGC) and the International Genomics of Alzheimer’s Project (IGAP) has fundamentally changed the approach to identify AD risk genes within APOE genotype subgroups. Dr. Jun is currently the Chair of three working groups in these consortia and has served as a Session Chair on multiple occasions at national and international conferences. Dr. Jun is currently a Director and Head of Neurogenetics and Integrated Genomics at the Andover Innovative Medicines (AiM) Institute, Eisai Inc., while maintaining a research program at BUSM that is independent of her role in the company. Since starting her current position in private industry in August 2015, Dr. Jun has developed an innovative and novel therapeutic concept for AD based on the well-established protective effect of the APOE ε2 allele. Currently, Dr. Jun is involved in several researches focusing on integrated genomics and innovative medicine for AD.
Understanding APOE Mediated Mechanism and Brain Omics Research:
APOE is the major risk gene for late onset Alzheimer’s disease. In US and international genetics consortium, Dr. Jun led and conducted innovative analysis approaches to identify distinct genetic signatures contributing to Alzheimer’s disease risk in APOE4-positive vs. APOE4-negative subgroups. This effort has reported one of the most striking discoveries in the Alzheimer’s disease genetics field that genetic variants in the MAPT/KANSL1 locus are strongly associated with Alzheimer’s disease among subjects who do not carry the APOE4 allele of the APOE gene (Jun et al. 2015). This is an important breakthrough in Alzheimer’s disease genetics, because for the first time APOE genotypes modulate effects of MAPT locus on Alzheimer’s disease risk. The follow-up analysis of the initial report (Jun et al. 2016) using APOE2-carrier subjects by separating from the APOE4-negative subgroup has discovered genetic variants in PPP2CB with strong genetic interaction with the APOE2 allele, where PPP2CB encodes a catalytic subunit of protein phosphatase 2A that is responsible about 71% of tau phosphatase activities in human brain (reducing tau phosphorylation). After the first report of APOE as the major genetic risk factor for Alzheimer’s disease in 1993, therapeutic concepts targeting APOE primarily involve in correcting or inhibiting the APOE4 effect, the risk factor for Alzheimer’s disease. For the first time, beyond APOE4, Dr. Jun has developed a novel therapeutic concept for Alzheimer’s disease that mimics the APOE2 protective mechanism. A five-year grant proposal based on this innovative idea was funded by the NIH/NIA starting in 2017 (RF1-AG057519; Multiple PIs: Farrer and Jun). In this project, we will perform functional experiments for connecting APOE2 protective mechanism to tau and conduct in vitro proof-of-concept experiments for developing new drugs for Alzheimer’s disease based on APOE-mediated protective mechanisms. After these findings, Dr. Jun published 5 papers deciphering APOE related disease mechanisms including one as last author (Reiman et al. Nature Communications 2020) and four as co-author (Ma et al. JAMA Neurology 2019; Choi et al. Journal of Clinical Medicine 2019; Arboleda-Velasquez et al. Nature Medicine 2019; Friedberg et al. Scientific Reports 2020).
Drug Discovery and Repurposing in Alzheimer’s Disease Therapeutics:
From 2015 to 2018, Dr. Jun served as a Director and Head of Neurogenetics and Integrated Genomics for Andover Innovative Medicines (AiM) Institute which is the Eisai company’s R&D unit for neurology and oncology in the US. Her role in the company was to identify Alzheimer’s disease drug targets by creating novel therapeutic concepts derived from human genetics and genomics data and help design proof-of-mechanism studies based on disease associated genetic variants and brain omics data collaborating with biologists and chemists. During her tenure with Eisai, she maintained my academic position at BUSM as an Adjunct Faculty in order to continue academic research programs. Dr. Jun developed a novel therapeutic concept predicated on the idea that Alzheimer’s disease could be delayed or prevented by elucidating and mimicking the protective mechanism of the APOE ε2 allele. Translational research for AD therapeutics remains her main focus and will occupy the majority of her effort. Dr. Jun has contributed to development of a large coordinated national initiative for AD therapeutics empowered by transformative Artificial Intelligence (AI) approaches using high throughput human big data, collaborating with national profit and non-profit institutes. Dr. Jun will serve as the Director of a ‘Genome-Guided Drug Discovery Core’ that will lead efforts on innovative drug discovery for AD, repurposing existing drugs, and developing a platform for open collaboration between academia and industry.
Ethnic Diversity Research in Alzheimer’s Disease:
Dr. Jun has directed the genetic analyses for several projects aimed at identifying Alzheimer’s disease genetic risk variants for Alzheimer’s disease in multi-ethnic cohorts, which led to 4 publications including co-first author on papers focused on European ancestry (Naj, Jun et al. Nature Genetics 2011) and Asian (Miyashita, Koike, Jun et al. PLos One 2013) populations, second author on a paper focused on African Americans (Reitz, Jun et al. JAMA 2013), and first author of a trans-ethnic study (Jun et al. Alzheimers & Dementia 2017). These studies emphasized shared and/or unique genetic signatures in different ethnic populations. These publications have significantly improved our understandings in effect sizes and frequencies of genetic risk variants for Alzheimer’s disease in multi-ethnic populations. Dr. Jun has been a project leader at the Alzheimer’s Disease Genetics Consortium to understand ethnic similarities and differences on genetic risk profiles for Alzheimer’s disease and influence of APOE in a transethnic approach. In January 2017, she has published the first report on trans-ethnic genetics for Alzheimer’s disease using the large number of multi-ethnic subjects. She has also contributed to the identification of a genetic modifier for the effect size of APOE4 homozygotes in Koreans. This report demonstrates the importance of investigating effect sizes of known Alzheimer’s disease genetic risk factors (i.e., APOE) as well as trans-ethnic profiles of genetic risk factors for Alzheimer’s disease using multi-ethnic datasets. Dr. Jun established an international collaborative network to share resources of Asian populations and coordinate research programs for Alzheimer’s disease using Asian populations. In addition, Dr. Jun initiated a collaboration between our research team at BUSM and a group at Chosun University in South Korea and will contribute to a funded project that will perform whole genome sequencing in a sample of 4,000 Korean Alzheimer’s disease cases and controls. Dr. Jun is a founding member of a large Asian Cohort for Alzheimer’s Disease (ACAD) Consortium that will recruit and study genetic and non-genetic risk factors for AD using Korean, Chinese, and Vietnamese Americans in US and Canada. In this consortium, she will lead the Analysis Core and recruit Korean American AD cases and controls in collaboration with investigators at the University of Massachusetts in Boston.
Innovative Genetic Studies in the Framingham Heart Study:
Dr. Jun has extensive worked on analyzing family-based genetic data in the Framingham Heart Study (FHS) leading to discoveries of two novel genes for Alzheimer’s disease, CTNND2 and PLXNA4. These findings were bolstered by functional studies performed in eye and brain tissue, respectively, by our BUSM collaborators. Claims for diagnostic and therapeutic applications of PLXNA4 have been filed at US Patent and Trademark Office (USSN: 14/889,565) and Patent Cooperation Treaty (PCT/US2014/037479). These discoveries also contributed to the basis of a newly funded U19 grant to NIH to establish a FHS Brain Aging Program (FHS-BAP). In this program, Dr. Jun will co-lead a project in the proposed program that will continue surveillance and examination of FHS participants for cognitive decline and dementia and the FHS brain donation program. This large program will also conduct research related to themes of identification of genetic factors and biomarkers for Alzheimer’s disease risk and resilience, and vascular/inflammatory precursors of Alzheimer’s disease.
US and International Alzheimer’s Disease Consortium Activities:
Dr. Jun helped build an outstanding research program of genetics and genomics for Alzheimer’s disease using large datasets from national and international consortia including the Alzheimer’s Disease Genetics Consortium (ADGC) and the International Genomics of Alzheimer’s Project (IGAP). For the past 10 years working, Dr. Jun is a key faculty to establish one of the strongest genetic and genomic data science teams studying Alzheimer’s disease genetics worldwide. She has been a core member of these large consortium teams evidenced by leading primary analysis and data management activities, many high profile papers including ones as lead or senior author, designing and writing large sections of grant applications to support the work of these and other Alzheimer’s disease genetic consortia, and reviewing applications from investigators worldwide who request access to ADGC datasets containing genetic and phenotypic information from tens of thousands of research subjects.
Assistant Professor, Biostatistics
Genetics & Genomics, PhD, Case Western Reserve University, 2008
Microbiology, MS, Seoul National University, 1999
Panitch R, Hu J, Chung J, Zhu C, Meng G, Xia W, Bennett DA, Lunetta KL, Ikezu T, Au R, Stein TD, Farrer LA, Jun GR. Integrative brain transcriptome analysis links complement component 4 and HSPA2 to the APOE e2 protective effect in Alzheimer disease. Mol Psychiatry. 2021 Sep 03. PMID: 34480088.Published on 4/30/2021
Loporchio DF, Tam EK, Cho J, Chung J, Jun GR, Xia W, Fiorello MG, Siegel NH, Ness S, Stein TD, Subramanian ML. Cytokine Levels in Human Vitreous in Proliferative Diabetic Retinopathy. Cells. 2021 04 30; 10(5). PMID: 33946446.Published on 1/1/2021
Kunkle BW, Schmidt M, Klein HU, Naj AC, Hamilton-Nelson KL, Larson EB, Evans DA, De Jager PL, Crane PK, Buxbaum JD, Ertekin-Taner N, Barnes LL, Fallin MD, Manly JJ, Go RCP, Obisesan TO, Kamboh MI, Bennett DA, Hall KS, Goate AM, Foroud TM, Martin ER, Wang LS, Byrd GS, Farrer LA, Haines JL, Schellenberg GD, Mayeux R, Pericak-Vance MA, Reitz C, Graff-Radford NR, Martinez I, Ayodele T, Logue MW, Cantwell LB, Jean-Francois M, Kuzma AB, Adams LD, Vance JM, Cuccaro ML, Chung J, Mez J, Lunetta KL, Jun GR, Lopez OL, Hendrie HC, Reiman EM, Kowall NW, Leverenz JB, Small SA, Levey AI, Golde TE, Saykin AJ, Starks TD, Albert MS, Hyman BT, Petersen RC, Sano M, Wisniewski T, Vassar R, Kaye JA, Henderson VW, DeCarli C, LaFerla FM, Brewer JB, Miller BL, Swerdlow RH, Van Eldik LJ, Paulson HL, Trojanowski JQ, Chui HC, Rosenberg RN, Craft S, Grabowski TJ, Asthana S, Morris JC, Strittmatter SM, Kukull WA. Novel Alzheimer Disease Risk Loci and Pathways in African American Individuals Using the African Genome Resources Panel: A Meta-analysis. JAMA Neurol. 2021 01 01; 78(1):102-113. PMID: 33074286.Published on 12/11/2020
Yonova-Doing E, Zhao W, Igo RP, Wang C, Sundaresan P, Lee KE, Jun GR, Alves AC, Chai X, Chan ASY, Lee MC, Fong A, Tan AG, Khor CC, Chew EY, Hysi PG, Fan Q, Chua J, Chung J, Liao J, Colijn JM, Burdon KP, Fritsche LG, Swift MK, Hilmy MH, Chee ML, Tedja M, Bonnemaijer PWM, Gupta P, Tan QS, Li Z, Vithana EN, Ravindran RD, Chee SP, Shi Y, Liu W, Su X, Sim X, Shen Y, Wang YX, Li H, Tham YC, Teo YY, Aung T, Small KS, Mitchell P, Jonas JB, Wong TY, Fletcher AE, Klaver CCW, Klein BEK, Wang JJ, Iyengar SK, Hammond CJ, Cheng CY. Common variants in SOX-2 and congenital cataract genes contribute to age-related nuclear cataract. Commun Biol. 2020 12 11; 3(1):755. PMID: 33311586.Published on 9/17/2020
Subramanian ML, Vig V, Chung J, Fiorello MG, Xia W, Zetterberg H, Blennow K, Zetterberg M, Shareef F, Siegel NH, Ness S, Jun GR, Stein TD. Neurofilament light chain in the vitreous humor of the eye. Alzheimers Res Ther. 2020 09 17; 12(1):111. PMID: 32943089.Published on 2/19/2020
Friedberg JS, Aytan N, Cherry JD, Xia W, Standring OJ, Alvarez VE, Nicks R, Svirsky S, Meng G, Jun G, Ryu H, Au R, Stein TD. Associations between brain inflammatory profiles and human neuropathology are altered based on apolipoprotein E e4 genotype. Sci Rep. 2020 02 19; 10(1):2924. PMID: 32076055.Published on 2/3/2020
Reiman EM, Arboleda-Velasquez JF, Quiroz YT, Huentelman MJ, Beach TG, Caselli RJ, Chen Y, Su Y, Myers AJ, Hardy J, Paul Vonsattel J, Younkin SG, Bennett DA, De Jager PL, Larson EB, Crane PK, Keene CD, Kamboh MI, Kofler JK, Duque L, Gilbert JR, Gwirtsman HE, Buxbaum JD, Dickson DW, Frosch MP, Ghetti BF, Lunetta KL, Wang LS, Hyman BT, Kukull WA, Foroud T, Haines JL, Mayeux RP, Pericak-Vance MA, Schneider JA, Trojanowski JQ, Farrer LA, Schellenberg GD, Beecham GW, Montine TJ, Jun GR. Exceptionally low likelihood of Alzheimer's dementia in APOE2 homozygotes from a 5,000-person neuropathological study. Nat Commun. 2020 02 03; 11(1):667. PMID: 32015339.Published on 11/4/2019
Arboleda-Velasquez JF, Lopera F, O'Hare M, Delgado-Tirado S, Marino C, Chmielewska N, Saez-Torres KL, Amarnani D, Schultz AP, Sperling RA, Leyton-Cifuentes D, Chen K, Baena A, Aguillon D, Rios-Romenets S, Giraldo M, Guzmán-Vélez E, Norton DJ, Pardilla-Delgado E, Artola A, Sanchez JS, Acosta-Uribe J, Lalli M, Kosik KS, Huentelman MJ, Zetterberg H, Blennow K, Reiman RA, Luo J, Chen Y, Thiyyagura P, Su Y, Jun GR, Naymik M, Gai X, Bootwalla M, Ji J, Shen L, Miller JB, Kim LA, Tariot PN, Johnson KA, Reiman EM, Quiroz YT. Resistance to autosomal dominant Alzheimer's disease in an APOE3 Christchurch homozygote: a case report. Nat Med. 2019 11; 25(11):1680-1683. PMID: 31686034.Published on 9/1/2019
Ma Y, Jun GR, Zhang X, Chung J, Naj AC, Chen Y, Bellenguez C, Hamilton-Nelson K, Martin ER, Kunkle BW, Bis JC, Debette S, DeStefano AL, Fornage M, Nicolas G, van Duijn C, Bennett DA, De Jager PL, Mayeux R, Haines JL, Pericak-Vance MA, Seshadri S, Lambert JC, Schellenberg GD, Lunetta KL, Farrer LA. Analysis of Whole-Exome Sequencing Data for Alzheimer Disease Stratified by APOE Genotype. JAMA Neurol. 2019 Sep 01; 76(9):1099-1108. PMID: 31180460.Published on 9/1/2019
Kunkle BW, Grenier-Boley B, Sims R, Bis JC, Damotte V, Naj AC, Boland A, Vronskaya M, van der Lee SJ, Amlie-Wolf A, Bellenguez C, Frizatti A, Chouraki V, Martin ER, Sleegers K, Badarinarayan N, Jakobsdottir J, Hamilton-Nelson KL, Moreno-Grau S, Olaso R, Raybould R, Chen Y, Kuzma AB, Hiltunen M, Morgan T, Ahmad S, Vardarajan BN, Epelbaum J, Hoffmann P, Boada M, Beecham GW, Garnier JG, Harold D, Fitzpatrick AL, Valladares O, Moutet ML, Gerrish A, Smith AV, Qu L, Bacq D, Denning N, Jian X, Zhao Y, Del Zompo M, Fox NC, Choi SH, Mateo I, Hughes JT, Adams HH, Malamon J, Sanchez-Garcia F, Patel Y, Brody JA, Dombroski BA, Naranjo MCD, Daniilidou M, Eiriksdottir G, Mukherjee S, Wallon D, Uphill J, Aspelund T, Cantwell LB, Garzia F, Galimberti D, Hofer E, Butkiewicz M, Fin B, Scarpini E, Sarnowski C, Bush WS, Meslage S, Kornhuber J, White CC, Song Y, Barber RC, Engelborghs S, Sordon S, Voijnovic D, Adams PM, Vandenberghe R, Mayhaus M, Cupples LA, Albert MS, De Deyn PP, Gu W, Himali JJ, Beekly D, Squassina A, Hartmann AM, Orellana A, Blacker D, Rodriguez-Rodriguez E, Lovestone S, Garcia ME, Doody RS, Munoz-Fernadez C, Sussams R, Lin H, Fairchild TJ, Benito YA, Holmes C, Karamujic-Comic H, Frosch MP, Thonberg H, Maier W, Roshchupkin G, Ghetti B, Giedraitis V, Kawalia A, Li S, Huebinger RM, Kilander L, Moebus S, Hernández I, Kamboh MI, Brundin R, Turton J, Yang Q, Katz MJ, Concari L, Lord J, Beiser AS, Keene CD, Helisalmi S, Kloszewska I, Kukull WA, Koivisto AM, Lynch A, Tarraga L, Larson EB, Haapasalo A, Lawlor B, Mosley TH, Lipton RB, Solfrizzi V, Gill M, Longstreth WT, Montine TJ, Frisardi V, Diez-Fairen M, Rivadeneira F, Petersen RC, Deramecourt V, Alvarez I, Salani F, Ciaramella A, Boerwinkle E, Reiman EM, Fievet N, Rotter JI, Reisch JS, Hanon O, Cupidi C, Uitterlinden AGA, Royall DR, Dufouil C, Maletta RG, de Rojas I, Sano M, Brice A, Cecchetti R, George-Hyslop PS, Ritchie K, Tsolaki M, Tsuang DW, Dubois B, Craig D, Wu CK, Soininen H, Avramidou D, Albin RL, Fratiglioni L, Germanou A, Apostolova LG, Keller L, Koutroumani M, Arnold SE, Panza F, Gkatzima O, Asthana S, Hannequin D, Whitehead P, Atwood CS, Caffarra P, Hampel H, Quintela I, Carracedo Á, Lannfelt L, Rubinsztein DC, Barnes LL, Pasquier F, Frölich L, Barral S, McGuinness B, Beach TG, Johnston JA, Becker JT, Passmore P, Bigio EH, Schott JM, Bird TD, Warren JD, Boeve BF, Lupton MK, Bowen JD, Proitsi P, Boxer A, Powell JF, Burke JR, Kauwe JSK, Burns JM, Mancuso M, Buxbaum JD, Bonuccelli U, Cairns NJ, McQuillin A, Cao C, Livingston G, Carlson CS, Bass NJ, Carlsson CM, Hardy J, Carney RM, Bras J, Carrasquillo MM, Guerreiro R, Allen M, Chui HC, Fisher E, Masullo C, Crocco EA, DeCarli C, Bisceglio G, Dick M, Ma L, Duara R, Graff-Radford NR, Evans DA, Hodges A, Faber KM, Scherer M, Fallon KB, Riemenschneider M, Fardo DW, Heun R, Farlow MR, Kölsch H, Ferris S, Leber M, Foroud TM, Heuser I, Galasko DR, Giegling I, Gearing M, Hüll M, Geschwind DH, Gilbert JR, Morris J, Green RC, Mayo K, Growdon JH, Feulner T, Hamilton RL, Harrell LE, Drichel D, Honig LS, Cushion TD, Huentelman MJ, Hollingworth P, Hulette CM, Hyman BT, Marshall R, Jarvik GP, Meggy A, Abner E, Menzies GE, Jin LW, Leonenko G, Real LM, Jun GR, Baldwin CT, Grozeva D, Karydas A, Russo G, Kaye JA, Kim R, Jessen F, Kowall NW, Vellas B, Kramer JH, Vardy E, LaFerla FM, Jöckel KH, Lah JJ, Dichgans M, Leverenz JB, Mann D, Levey AI, Pickering-Brown S, Lieberman AP, Klopp N, Lunetta KL, Wichmann HE, Lyketsos CG, Morgan K, Marson DC, Brown K, Martiniuk F, Medway C, Mash DC, Nöthen MM, Masliah E, Hooper NM, McCormick WC, Daniele A, McCurry SM, Bayer A, McDavid AN, Gallacher J, McKee AC, van den Bussche H, Mesulam M, Brayne C, Miller BL, Riedel-Heller S, Miller CA, Miller JW, Al-Chalabi A, Morris JC, Shaw CE, Myers AJ, Wiltfang J, O'Bryant S, Olichney JM, Alvarez V, Parisi JE, Singleton AB, Paulson HL, Collinge J, Perry WR, Mead S, Peskind E, Cribbs DH, Rossor M, Pierce A, Ryan NS, Poon WW, Nacmias B, Potter H, Sorbi S, et al. Author Correction: Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates Aß, tau, immunity and lipid processing. Nat Genet. 2019 Sep; 51(9):1423-1424. PMID: 31417202.