Gyungah Jun, Ph.D.
Assistant Professor, Biomedical Genetics Section, Department of Medicine, Boston University School of Medicine
Assistant Professor, Dept of Biostatistics, Boston University School of Public Health
Adjunct Assistant Professor, Dept of Epidemiology and Biostatistics, School of Medicine, Case Western Reserve University
Ph.D. Epidemiology and Biostatistics, School of Medicine,
Case Western Reserve University, Cleveland, OH
M.C.I.S. Computer and Information Science, Cleveland State University, Cleveland, OH
M.S. Microbiology and Immunology, Seoul National University, Seoul, South Korea
B.A. Agricultural Biology, Korea University, Seoul, South Korea
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 Medicine2019; 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.
For complete list of published work in MyBibliography: https://www.ncbi.nlm.nih.gov/myncbi/1V54Hz2C9wFkJ/bibliography/public/
Selected publications related to key researches (reverse chronological order; *co-first author):
- 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 ɛ4 genotype. Scientific Reports. 2020;10:2924. PMID: 32076055.
- 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; Alzheimer’s Disease Genetics Consortium. Exceptionally low likelihood of Alzheimer’s dementia in APOE2 homozygotes from a 5,000-person neuropathological study. Nat Commun. 2020 Feb 3;11(1):667. PMID: 32015339.
- 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 Nov;25(11):1680-1683. PMID: 31686034.
- Choi KY, Lee JJ, Gunasekaran TI, Kang S, Lee W, Jeong J, Lim HJ, Zhang X, Zhu C, Won SY, Choi YY, Seo EH, Lee SC, Gim J, Chung JY, Chong A, Byun MS, Seo S, Ko PW, Han JW, McLean C, Farrell J, Lunetta KL, Miyashita A, Hara N, Won S, Choi SM, Ha JM, Jeong JH, Kuwano R, Song MK, An SSA, Lee YM, Park KW, Lee HW, Choi SH, Rhee S, Song WK, Lee JS, Mayeux R, Haines JL, Pericak-Vance MA, Choo ILH, Nho K, Kim KW, Lee DY, Kim S, Kim BC, Kim H, Jun GR, Schellenberg GD, Ikeuchi T, Farrer LA, Lee KH, Neuroimaging Initative AD. APOE Promoter Polymorphism-219T/G is an Effect Modifier of the Influence of APOE ε4 on Alzheimer’s Disease Risk in a Multiracial Sample. J Clin Med. 2019 Aug 16;8(8). PMID: 31426376.
- Ma Y, Jun GR, et al. CpG-related SNPs in the MS4A Region have a Dose-Dependent Effect on Risk of Late-onset Alzheimer Disease. Aging Cell. 2019 Aug;18(4):e12964. PMID: 31144443.
- Ma Y, Jun GR, et al. Novel Alzheimer’s Disease Identified in Subsets of Whole Exome Sequencing Data Stratified by APOE Genotype. JAMA Neurol. 2019 Jun 10. PMID: 31180460.
- Chung J, Zhang X, Allen M, Wang X, Ma Y, Beechan G, Montine TJ, Golde TE, Price ND, Ertekin-Taner N, Junetta KL, Mez J, Alzheimer’s Disease Genetics Consortium, Mayeux R, Haines JL, Pericak-Vance MA, Schellenberg G, Jun GR, Farrer LA. Genome-wide pleiotropy analysis of neuropathological traits related to Alzheimer’s disease. Alzheimers Res Ther. 2018 Feb 20;10(1):22. PMID: 29458411.
- Chung J, Jun GR, Dupuis J, Farrer LA. Comparison of methods for multivariate gene-based association tests for complex diseases using common variants. Eur J Hum Genet. 2019 Jan 25. PMID: 30683923.
- Chung J, Wang X, Maruyama T, Ma Y, Zhang X, Mez J, Sherva R, Takeyama H, ADNI, Lunetta KL, Farrer LA, Jun GR. Genome-wide association study of Alzheimer’s disease endophenotypes at prediagnosis stages. Alzheimers Dement. 2017 Dec 20. pii: S1552-5260(17)33842-6. doi: 10.1016/j.jalz.2017.11.006. PMID: 29274321.
- Jun GR, Chung J, Mez J, Barber R, Beecham GW, Bennett DA, Buxbaum JD, Byrd GS, Carrasquillo MM, Crane PK, Cruchaga C, De Jager P, Ertekin-Taner N, Evans D, Fallin MD, Foroud TM, Friedland RP, Goate AM, Graff-Radford NR, Hendrie H, Hall KS, Hamilton-Nelson KL, Inzelberg R, Kamboh MI, Kauwe JSK, Kukull WA, Kunkle BW, Kuwano R, Larson EB, Logue MW, Manly JJ, Martin ER, Montine TJ, Mukherjee S, Naj A, Reiman EM, Reitz C, Sherva R, St George-Hyslop PH, Thornton T, Younkin SG, Vardarajan BN, Wang LS, Wendlund JR, Winslow AR; Alzheimer’s Disease Genetics Consortium, Haines J, Mayeux R, Pericak-Vance MA, Schellenberg G, Lunetta KL, Farrer LA. Transethnic genome-wide scan identifies novel Alzheimer disease loci. Alzheimers Dement. 2017;13(7):727-738. PMID: 28183528.
- Mez J, Chung J, Jun G, et al. Two novel loci, COBL and SLC10A2, for Alzheimer’s disease in African Americans. Alzheimers Dement. 2017;13(2):119-129. PMID: 27770636.
- Jun G, et al. A novel Alzheimer disease locus located near the gene encoding tau protein. Mol Psychiatry. 2016;21:108-17. PMID: 25778476.
- Jun G, et al. PLXNA4 is associated with Alzheimer disease and modulates tau phosphorylation. Ann Neurol. 2014;76(3):379-92. PMID: 25043464.
- Naj AC, Jun G, et al. Effects of multiple genetic loci on age at onset in late-onset Alzheimer disease: a genome-wide association study. JAMA Neurol. 2014; 71(11):1394-404. PMID: 25199842.
- Reitz C, Jun G, et al. Variants in the ATP-binding cassette transporter (ABCA7), Apolipoprotein E e4, and the risk of late-onset Alzheimer’s disease in African Americans. 2013;309(14):1483-92. PMID: 23571587.
- Miyashita A*, Koike A*, Jun G*, et al. SORL1 is genetically associated with late-onset Alzheimer’s disease in Japanese, Koreans, and Caucasians. PLoS One. 2013;8(4):e58618. PMID: 23565137.
- Jun G, Moncaster JA, Koutras C, Seshadri S, Buros J, McKee AC, Levesque G, Wolf PA, George-Hyslop P, Goldstein LE, Farrer LA. 2012. Delta-Catenin is genetically and biologically associated with cortical cataract and future Alzheimer-related structural and functional brain changes. PLoS One. 2012;7(9):e43728. PMID: 22984439.
- Jun G, Vardarajan BN, Buros J, Yu CE, Hawk MV, Dombroski BA, Crane PK, Larson EB; Alzheimer’s Disease Genetics Consortium, Mayeux R, Haines JL, Lunetta KL, Pericak-Vance MA, Schellenberg GD, Farrer LA. 2012. A comprehensive search for Alzheimer disease susceptibility loci in the APOE region. Arch Neurol. 2012; 69;1270-1279. PMID: 22869155.
- Jun G, Nicolaou M, Morrison MA, Buros J, Morgan DJ, Radeke MJ, Yonekawa Y, Tsironi EE, Kotoula MG, Zacharaki F, Mollema N, Yuan Y, Miller JW, Haider NB, Hageman GS, Kim IK, Schaumberg DA, Farrer LA, DeAngelis MM. Influence of ROBO1 and RORA on Risk of Age-related Macular Degeneration Reveals Genetically Distinct Phenotypes in Disease Pathophysiology. PLoS One. 2011;6(10):e25775. PMID: 21998696.
- Naj AC*, Jun G*, et al. Common variants in MS4A4/MS4A6E, CD2AP, CD33, and EPHA1 are associated with late-onset Alzheimer’s disease. Nat Genet. 2011;43(5):436-41. PMID: 21460841.
- Jun G, Naj AC, Beecham GW, Wang LS, Buros J, Gallins PJ, Buxbaum JD, Ertekin-Taner N, Fallin MD, Friedland R, Inzelberg R, Kramer P, Rogaeva E, St George-Hyslop P; Alzheimer’s Disease Genetics Consortium, Cantwell LB, Dombroski BA, Saykin AJ, Reiman EM, Bennett DA, Morris JC, Lunetta KL, Martin ER, Montine TJ, Goate AM, Blacker D, Tsuang DW, Beekly D, Cupples LA, Hakonarson H, Kukull W, Foroud TM, Haines J, Mayeux R, Farrer LA, Pericak-Vance MA, Schellenberg GD. Meta-analysis confirms CR1, CLU, and PICALM as Alzheimer’s disease risk loci and reveals interactions with APOE genotypes. Arch Neurol. 2010;67(12):1473-84. PMID: 20697030.