The DeAngelis Laboratory
Dr. DeAngelis has focused her career on vision research since 1999 when she received a post-doctoral fellowship training grant on macular degeneration as part of the Molecular Basis of Eye Disease program at Harvard Medical School. Working in collaboration with clinicians, she recruited and developed a large patient population of families to study the genetic and epidemiologic underpinnings of age-related macular degeneration (AMD), the leading cause of blindness in individuals over age fifty. The DeAngelis’ group has been utilizing a systems-biology-based genomic convergence approach to pinpoint disease causality for AMD. To this end, utilizing both families and unrelated case-controls to study DNA, gene expression, and protein, coupled with epidemiological information, her group identified two novel AMD associated genes, RORA and ROBO, in three diverse patient populations. Moreover, RORA was shown to interact with other established AMD genetic risk factors, ARMS2/HTRA1, thus furthering the development of a unifying hypothesis underlying AMD pathophysiology. Her laboratory continues to utilize systems-based biological approaches, including identifying functional variants as well as key regulatory elements in genes (or sets of genes) in an effort to develop appropriate, preventive, and therapeutic targets for this devastating form of blindness. Dr. DeAngelis has recruited and characterized ethnically diverse populations (including the underserved) throughout the world in an effort to understand the origin and significance of genetic variation and environmental factors associated with AMD as well as other blinding diseases such as diabetic retinopathy and hypertensive retinopathy. Recently, our laboratory has begun to examine the functional significance of the observed genetic associations in age-related macular degeneration, employing whole genome RNA-Seq and targeted bisulfite sequencing on fresh donor eye tissue and cell lines from these donor patients.
Hear Dr. DeAngelis speak about "The Role of Vitamin D Metabolism and BMI in Women's Health" at the WomensEyeHealthorg annual ARVO meeting update on AMD, May 5, 2013 on You Tube: www.youtube.com/watch?v=PlW-aVNsrbA
Patient Care Significance:
In the United States, AMD is the leading cause of blindness in those more than 50 years in age. By better understanding how genes and environmental factors interact to create disease, Dr. DeAngelis hopes to develop health-informed drug delivery that gets to underlying causes, ultimately helping to cure and prevent disease.
Postdoctoral Fellow, Ophthalmology, Harvard Medical School - Thaddeus P. Dryja, M.D., Boston, MA
Ph.D., Neuroscience, Louisiana State University Medical Center, School of Graduate Studies, New Orleans, LA
M.S., Physiology, Medical College of Virginia, Richmond, VA B.A., Environment, Technology and Society, Clark University, Worcester, MA
American Society of Human Genetics
Association for Research in Vision and Ophthalmology
International Genetic Epidemiology Society
Associate Professor of Ophthalmology & Visual Sciences-University of Utah School of Medicine
A Sample of Publications from the DeAngelis Laboratory:
Fritsche LG, Chen W, Schu M, Yaspan BL, Yu Y, Thorleifsson G, Zack DJ, Arakawa S, Cipriani V, Ripke S, Igo RP Jr, Buitendijk GH, Sim X, Weeks DE, Guymer RH, Merriam JE, Francis PJ, Hannum G, Agarwal A, Armbrecht AM, Audo I, Aung T, Barile GR, Benchaboune M, Bird AC, Bishop PN, Branham KE, Brooks M, Brucker AJ, Cade WH, Cain MS, Campochiaro PA, Chan CC, Cheng CY, Chew EY, Chin KA, Chowers I, Clayton DG, Cojocaru R, Conley YP, Cornes BK, Daly MJ, Dhillon B, Edwards AO, Evangelou E, Fagerness J, Ferreyra HA, Friedman JS, Geirsdottir A, George RJ, Gieger C, Gupta N, Hagstrom SA, Harding SP, Haritoglou C, Heckenlively JR, Holz FG, Hughes G, Ioannidis JP, Ishibashi T, Joseph P, Jun G, Kamatani Y, Katsanis N, N Keilhauer C, Khan JC, Kim IK, Kiyohara Y, Klein BE, Klein R, Kovach JL, Kozak I, Lee CJ, Lee KE, Lichtner P, Lotery AJ, Meitinger T, Mitchell P, Mohand-Saïd S, Moore AT, Morgan DJ, Morrison MA, Myers CE, Naj AC, Nakamura Y, Okada Y, Orlin A, Ortube MC, Othman MI, Pappas C, Park KH, Pauer GJ, Peachey NS, Poch O, Priya RR, Reynolds R, Richardson AJ, Ripp R, Rudolph G, Ryu E, Sahel JA, Schaumberg DA, Scholl HP, Schwartz SG, Scott WK, Shahid H, Sigurdsson H, Silvestri G, Sivakumaran TA, Smith RT, Sobrin L, Souied EH, Stambolian DE, Stefansson H, Sturgill-Short GM, Takahashi A, Tosakulwong N, Truitt BJ, Tsironi EE, Uitterlinden AG, van Duijn CM, Vijaya L, Vingerling JR, Vithana EN, Webster AR, Wichmann HE, Winkler TW, Wong TY, Wright AF, Zelenika D, Zhang M, Zhao L, Zhang K, Klein ML, Hageman GS, Lathrop GM, Stefansson K, Allikmets R, Baird PN, Gorin MB, Wang JJ, Klaver CC, Seddon JM, Pericak-Vance MA, Iyengar SK, Yates JR, Swaroop A, Weber BH, Kubo M, Deangelis MM, Léveillard T, Thorsteinsdottir U, Haines JL, Farrer LA, Heid IM, Abecasis GR; AMD Gene Consortium. Seven new loci associated with age-related macular degeneration. Nat Genet. 2013 Apr;45(4):433-9, 439e1-2. doi: 10.1038/ng.2578. Epub 2013 Mar 3.
Jacobo SM, Deangelis MM, Kim IK, Kazlauskas A. Age-related macular degeneration-associated silent polymorphisms in HtrA1 impair its ability to antagonize insulin-like growth factor 1.
Mol Cell Biol. 2013 May;33(10):1976-90. doi: 10.1128/MCB.01283-12. Epub 2013 Mar 11.
Ahmed F, Kamae KK, Jones DJ, Deangelis MM, Hageman GS, Gregory MC, Bernstein PS. Temporal macular thinning associated with x-linked alport syndrome. JAMA Ophthalmol. 2013 Jun 1;131(6):777-82. doi: 10.1001/jamaophthalmol.2013.1452.
Daniels AB, Lee JE, MacConaill LE, Palescandolo E, Van Hummelen P, Adams SM, DeAngelis MM, Hahn WC, Gragoudas ES, Harbour JW, Garraway LA, Kim IK. High throughput mass spectrometry-based mutation profiling of primary uveal melanoma.Invest Ophthalmol Vis Sci. 2012 Oct 9;53(11):6991-6. doi: 10.1167/iovs.12-10427.
Silveira AC, Morrison MA, Ji F, Xu H, Reinecke JB, Adams SM, Arneberg TM, Janssian M, Lee JE, Yuan Y, Schaumberg DA, Kotoula MG, Tsironi EE, Tsiloulis AN, Chatzoulis DZ, Miller JW, Kim IK, Hageman GS, Farrer LA, Haider NB, DeAngelis MM. (2010). Convergence of linkage, gene expression and association data demonstrates the influence of the RAR-related orphan receptor alpha (RORA) gene on neovascular AMD: a systems biology based approach. Vision Res, 50(7), 698-715.
Andreoli MT, Morrison MA, Kim BJ, Chen L, Adams SM, Miller JW, DeAngelis MM, Kim IK. (2009). Comprehensive analysis of complement factor H and LOC387715/ARMS2/HTRA1 variants with respect to phenotype in advanced age-related macular degeneration. Am J Ophthalmol, 148(6), 869-74.
Yan T, Yang YN, Cheng X, DeAngelis MM, Hoh J, Zhang H. (2009). Genotypic association analysis using discordant-relative-pairs. Ann Hum Genet, 73(1), 84-94.
Deangelis MM, Ji F, Adams S, Morrison MA, Harring AJ, Sweeney MO, Capone A Jr, Miller JW, Dryja TP, Ott J, Kim IK. (2008). Alleles in the HtrA serine peptidase 1 gene alter the risk of neovascular age-related macular degeneration. Ophthalmology, 115(7), 1209-1215.e7.
Yu HG, Liu X, Kiss S, Connolly E, Gragoudas ES, Michaud NA, Bulgakov OV, Adamian M, DeAngelis MM, Miller JW, Li T, Kim IK. (2008). Increased choroidal neovascularization following laser induction in mice lacking lysyl oxidase-like 1. Invest Ophthalmol Vis Sci, 49(6), 2599-605.
Zhang H, Morrison MA, Dewan A, Adams S, Andreoli M, Huynh N, Regan M, Brown A, Miller JW, Kim IK, Hoh J, Deangelis MM. (2008). The NEI/NCBI dbGAP database: genotypes and haplotypes that may specifically predispose to risk of neovascular age-related macular degeneration. BMC Med Genet, 9, 51.
Fan BJ, Pasquale L, Grosskreutz CL, Rhee D, Chen T, DeAngelis MM, Kim I, del Bono E, Miller JW, Li T, Haines JL, Wiggs JL. (2008). DNA sequence variants in the LOXL1 gene are associated with pseudoexfoliation glaucoma in a U.S. clinic-based population with broad ethnic diversity. BMC Med Genet, 9, 5.
Kim IK, Ji F, Morrison MA, Adams SM, Zhang Q, Lane AM, Capone A, Dryja TP, Ott J, Miller JW, DeAngelis MM. Comprehensive Analysis of CRP, CFH Y402H Genotype, BMI, diabetes and smoking on risk of neovascular age-related macular degeneration. Molecular Vision. 2008; 14:1487-1495.
Zhang H, Morrison MA, DeWan A, Adams SM, Andreoli M, Huynh N, Regan M, Brown A, Miller JW, Kim IK, Hoh J, DeAngelis MM. The NEI/NCBI dbGAP database: genotypes and haplotypes that may predispose to risk of neovascular age-related macular degeneration. BMC Medical Genetics. 2008 Jun 9;9(1):51. PMID: 18541031
Yu HG, Liu X, Kiss S, Connolly E, Gragoudas ES, Michaud N, Bulgakov O, Adamian M, DeAngelis MM, Miller JW, Li T, Kim IK. Increased Choroidal Neovascularization Following Laser Induction in Mice Lacking Lysyl oxidase-like 1. Invest Ophthalmol Vis Sci. 2008 Jun;49(6):2599-605. PMID: 18296663
Fan BJ, Pasquale L, Grosskreutz CL, Rhee D, Chen T, DeAngelis MM, Kim I, del Bono E, Miller JW, Li T, Haines JL, Wiggs JL. DNA sequence variants in the LOXL1 gene are associated with pseudoexfoliation glaucoma in a U.S. clinic-based population with broad ethnic diversity. BMC Medical Genetics 2008; Feb 6;9:5. PMID: 18254956
DeAngelis MM, Ji F, Adams SM, Morrison MA, Harring AJ, Sweeney MO, Capone A, Miller JW, Dryja, TP, and Kim, IK. Alleles in HTRA serine Peptidase 1 gene both reduce and increase risk of neovascular age-related macular degeneration independent of the Complement factor H gene and smoking. Ophthalmology 2008; Jul;115(7):1209-1215. PMID:18164066