Margaret M. DeAngelis, Ph.D.
Assistant Professor of Ophthalmology
Director, Ocular Molecular Genetics Institute
margaret_deangelis@meei.harvard.edu
Ocular Molecular Genetics Institute
The laboratory’s main research focus is elucidating the genetic and epidemiological factors that may underlie eye diseases of complex inheritance such as age-related macular degeneration (AMD). In the United States, AMD is the leading cause of blindness in those over 50 years of age. Together with Dr Ivana Kim and Dr. Joan Miller, we recruit patients for these studies that include cases and controls as well as extremely discordant sibpairs. Extremely discordant sibpairs are comprised of a patient with the neovascular form of AMD in at least one eye who has at least one living sibling without any AMD and is at least 65 years or older. We are also recruiting cohorts to study disease severity and progression for AMD.
AMD is a multifactorial disease and the sibpair method is one of the most powerful approaches for revealing factors that individually may have only modest effects on disease risk. To complement our ongoing genetic and epidemiological work, we are also conducting gene expression microarray and proteomic studies in order to examine the functional significance of disease-associated genetic variation. We have expanded our efforts to include other retinal diseases such as retinopathy of prematurity and polypoidal vasculopathy. Our ultimate goal is to correlate genotype with phenotype so that appropriate therapeutic targets can be developed with the hope of curing and preventing disease.
Selected Publications:
1. Potashner SJ, Dymczyk L, DeAngelis MM. D-aspartate uptake and release in the guinea pig spinal cord after partial ablation of the cerebral cortex. Journal of Neurochemistry 1988; 50(1): 103-111. PMID: 2891783
2. DeAngelis MM, Hayes RL, Lyeth BG. Traumatic Brain Injury causes a decrease in M2 muscarinic cholinergic receptor binding in the rat brain. Brain Research 1994; 653:39-44. PMID: 7982073
3. Hudson TJ, Stein LD, Gerety SS, Ma J, Castle AB, Silva J, Slonim DK, Baptista R, Kruglyak L, Xu S-H, Hu X, Colbert AME, Rosenberg C, Reeve-Daly MP, Rozen S, Hui L, Wu X, Vestergard C, Wilson KM, Bae JS, Maitra S, Ganiatsas S, Evans CA, DeAngelis MM, Ingalls KA, Nahf RW, Horton LT, Anderson MO, Collymore AJ, Ye W, Kouyoumjian V, Zemsteva IS, Tam J, Devine R, Courtney DF, Renaud MT, Nguyen M, O’Connor TJ, Fizames C, Faure S, Gyapay G, Dib C, Morissette J, Orlin JB, Birren BW, Goodman N, Weissenbach J, Hawkins TL, Foote S, Page DC, and Lander ES. An STS-Based Map of the Human Genome. Science 1995; 270: 1945-1954. PMID: 8533086
4. DeAngelis MM, Wang DG, Hawkins TL. Solid-phase reversible immobilization for the isolation of PCR products. Nucleic Acids Research 1995; 23: 4742-4743. PMID: 8524672
5. Dietrich WF, Miller J, Steen R, Merchant MA, Damron-Boles D, Husain Z, Dredge R, Daly MJ, Ingalls KA, O’Connor TJ, Evans CA, DeAngelis MM, Levinson DM, Kruglyak L, Goodman N, Copeland NG, Jenkins NA, Hawkins TL, Stein L, Page DC, Lander ES. A comprehensive genetic map of the mouse genome. Nature 1996; 380: 149-152. PMID: 8600386
6. Arcot SS, DeAngelis MM, Sherry ST, Adamson AW, Lamerdin JE, Deininger PL, Carrano AV, Batzer MA. Identification and characterization of two polymorphic Ya5 Alu repeats. Mutation Research 1997; 382: 5-11. PMID: 9360633
7. Bouyge-Moreau I, Rondeau G, Avet-Loiseau H, M-T André M-T, Bézieau S, Chérel M, Saleün S, Cadoret E, Shaikh T, DeAngelis MM, Arcot S, Batzer M, Moisan J-P, Devilder M-C. Construction of a 780-kb PAC, BAC and cosmid contig encompassing the minimal critical deletion involved in B cell Chronic Lymphocytic Leukemia at 13q14.3. Genomics 1997; 46: 183-190. PMID: 9417905
8. DeAngelis MM, Doucet JP, Drury S, Sherry ST, Robichaux MB, Den Z, Pelias MZ, Ditta GM, Keats BJB, Deininger PL, Batzer MA. Assembly of a high-resolution map of the Acadian Usher syndrome region and localization of the nuclear EF-hand acidic gene. Biochimica et Biophysica Acta 1998; 1407(1): 84-91. PMID: 9639681
9. Vinas AM, Drury SS, DeAngelis MM, Den Z, Huang JM, Berlin CI, Hunt JD, Batzer MA, Deininger PL, Keats BJB. The mouse deafness locus (dn) is associated with an inversion on Chromosome 19. Biochimica et Biophysica Acta 1998; 1407: 257-262. PMID: 9748617
10. Scott DA, Greinwald Jr. JH, Marietta JR, Drury S, Swiderski RE, Vinas A, DeAngelis MM, Carmi R, Ramesh A, Kraft ML, Elbedour K, Skworak AB, Friedman RA, Srikumari Srisailapathy CR, Verhoeven K, Van Camp G, Lovett M, Deininger PL, Batzer MA, Morton CC, Keats BJ, Smith RJH, Sheffield VC. Identification and mutation analysis of a cochlear-expressed, zinc finger protein gene at the DNFB7/11 and dn hearing-loss-loci on human chromosome 9q and mouse chromosome 19. Gene 1998; 215: 461-469. PMID: 9758550
11. Pelias MZ, DeAngelis MM. The New Genetic Technologies: New Options, New Hope, and New Challenges. Loyola Law Review 1999; 45: 287-306. PMID: 16622958
12. DeAngelis MM, McGee TL, Keats BJB, Slim R, Berson EL, Dryja TP. Two families from New England with usher syndrome type IC with distinct haplotypes. American Journal of Ophthalmology 2001; 131(3):355-358. PMID: 11239869
13. DeAngelis MM, Grimsby JL, Sandberg MA, Berson EL, Dryja TP. Novel Mutations in the NRL gene and associated clinical findings in patients with dominant retinitis pigmentosa. Archives of Ophthalmology 2002; 120 (3):369-375. PMID: 11879142
14. Rivolta C, Sharon D, DeAngelis MM, Dryja TP. Retinitis Pigmentosa and allied diseases: numerous diseases, genes and inheritance patterns. Human Molecular Genetics 2002; 11(10):1219-1227. PMID: 12015282
15. DeAngelis MM, Lane A-M, Shah CP, Ott J, Dryja TP, Miller JW. Extremely discordant sib-pair study design to determine risk factors for neovascular age-related macular degeneration. Archives of Ophthalmology 2004; 122 (4):575-580. PMID: 15078676
16. DeAngelis MM. Retinitis Pigmentosa and Common Variable Immunodeficiency Disease: Associated or Separate? Southern Medical Journal 2006; 99 (9):914. PMID: 17004520
17. DeAngelis MM, Ji F, Kim I, Adams S, Capone A, Ott J, Miller JW, Dryja TP. Cigarette Smoking, CFH, APOE, ELOVL4, and Risk of Neovascular Age-Related Macular Degeneration. Archives of Ophthalmology 2007; 125(1):49-54. PMID: 17210851
18. 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
19. 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
20. 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
21. 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
21. 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.
