The DeAngelis Laboratory
With a Ph.D. in neuroscience, Dr. DeAngelis' main research focus is to uncover the genetic and epidemiological factors that may underlie eye diseases of complex inheritance like age-related macular degeneration.
To do this, she recruits patients for studies who are "discordant sibpairs," or siblings age 65-years and older where one has AMD in at least one eye and the other does not. Because many factors contribute to AMD, the sibpair method is one of the most powerful approaches for revealing factors that individually may have only modest effects on disease risk.
Dr. DeAngelis has several cohorts located around the world to study sibpairs and the severity and progression of AMD, including groups in Utah, New Zealand, Greece, Nepal and Timor. To complement her ongoing genetic and epidemiological work, she also conducts gene expression microarray and proteomic - microscopic and large-scale - studies on the functional significance of disease-associated genetic variation.
The ultimate goal of Dr. DeAngelis' research is to correlate genotype with phenotype so that targeted treatments can be developed in hopes of curing and preventing disease.
Previously Dr. DeAngelis was an Assistant Professor in the Department of Ophthalmology at Harvard Medical School/Massachusetts Eye and Ear Infirmary.
Dr. DeAngelis focused her career on vision research in 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).
As a result Dr. DeAngelis is a Principal Investigator of a competitive renewal from the National Eye Institute to study the molecular genetics of AMD. Dr. DeAngelis has also received awards for her work in this field including the Lincy Award, Milton Award, Massachusetts Lion's Award and the Thome Foundation Memorial Award.
In addition to studying genetic susceptibility to AMD, her group, working in collaboration with Dr. Hageman, also at the John A. Moran Eye Center, is utilizing a systems biology based approach to pinpoint disease causality by elucidating key regulatory components in pathways or sets of genes which are implicated in AMD. Their aim is to develop appropriate preventive and therapeutic targets to cure this devastating form of blindness. To that end, her group identified a novel anti-angiogenic AMD associated gene known as RORA that is protective against the development of neovascular AMD in 3 diverse patient populations. Moreover, RORA was shown by their groups to interact with other known AMD genetic risk factors thus furthering the development of a unifying hypothesis underlying AMD pathophysiology.
The success of this work is the result of building strong collaborations between scientists and clinicians both from outside and within the Moran community.
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:
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