Professor, Laboratory of Molecular Psychiatry, Psychiatry & Human Behavior
School of Medicine

Genomics of cognitive traits, Brain evolution and paleoneurology, Genetics of language, Computational neurogenomics

Center for Epigenetics and Metabolism- UCI

UCI Center for Autism Research and Treatment (UCI CART)

1989-1990 Postdoc, Human Molecular Genetics, Yale University, New Haven, CT

My current research activities are centered on the analysis of the function and evolution of genes in neurocognitive complex traits, using next-generation DNA and RNA sequencing methods, integrated with a biostatistical and computational approach. In the last 10 years I developed Next Generation Sequencing (NGS) methods to detect and characterize the role of TEs as epigenetic regulatory elements of gene expression in neural tissue and across neuropsychiatric psychiatric disorders. In particular, my lab has identified and characterized the role of Transposable Elements (TEs: DNA elements that can move within the genome) as major epigenetic regulators (alternative promoters, enhancers, insulators) of gene expression. We have been the first lab to systematically analyze non-reference and de novo LINE1s (L1s) in postmortem tissue of neuropsychiatric patients, proving that the distribution of their retro-transpositions are different in healthy subjects compared to schizophrenic patients (Guffanti et al, 2016). We have developed molecular and bioinformatics tools to quantify the expression of TEs in neural tissues, detected more than 600,000 expressed discrete TEs in the human frontal lobe and found that their altered expressions contribute to schizophrenia and autism, through a possible dysregulation of neurodevelopmental gene pathways (1R21MH115327-01; Guffanti et al, MBE 2018).
I have worked in the field of Alzheimer’s Disease genetics since 1992 when we mapped and identified the first gene for familial AD (PSEN1). My lab among the first to detect CNVs in Late Onset AD. Recently, we found upregulation of TEs in blood of subjects that will develop clinical AD within 12-48 months, making these TEs potentially useful biomarkers of the disorder.
Over many years, it has become evident that the regulatory genome and its associated epigenetic mechanisms are the most relevant factors in the genomics of cognitive evolution and development, as well as in related disorders. With a few rare exceptions, we never found any coding variant that could explain more than a negligible fraction of the total genetic risk for any cognitive disorder. We are progressively better understanding that ncRNAs are key epigenetic players in the making of gene regulatory networks: my lab has contributed to identify many brain-specific regulatory ncRNAs, thus offering new perspectives for applications of precision medicine

2000 NARSAD Independent Investigator Award

See the complete list of publications at https://www.ncbi.nlm.nih.gov/myncbi/1jkA2ccph7nQf/bibliography/public/

H-index:
80 (Google Scholar)
65 (Web of Science)

Tilot AK, Khramtsova EA, Liang D, Grasby KL, Jahanshad N, Painter J, Colodro-Conde L, Bralten J, Hibar DP, Lind PA, Liu S, Brotman SM, Thompson PM, Medland SE, Macciardi F, Stranger BE, Davis LK, Fisher SE, Stein JL. (2020). The Evolutionary History of Common Genetic Variants Influencing Human Cortical Surface Area. Cereb Cortex. 2020 doi: 10.1093/cercor/bhaa327. PMID: 33290510

Mapstone M, Gross TJ, Macciardi F, Cheema AK, Petersen M, Head E, Handen BL, Klunk WE, Christian BT, Silverman W, Lott IT, Schupf N; Alzheimer's Biomarkers Consortium–Down Syndrome (ABC-DS) Investigators. (2020). Metabolic correlates of prevalent mild cognitive impairment and Alzheimer's disease in adults with Down syndrome. Alzheimers Dement (Amst). 2020 12(1):e12028. doi: 10.1002/dad2.12028. PMID: 32258359

Grasby KL, Jahanshad N, Painter JN, Colodro-Conde L, Bralten J, Hibar DP, Lind PA, Pizzagalli F, Ching CRK, McMahon MAB, Shatokhina N, Zsembik LCP, Thomopoulos SI, Zhu AH, Strike LT, Agartz I, Alhusaini S, Almeida MAA, Alnæs D, Amlien IK, Andersson M, Ard T, Armstrong NJ, Ashley-Koch A, Atkins JR, Bernard M, Brouwer RM, Buimer EEL, Bülow R, Bürger C, Cannon DM, Chakravarty M, Chen Q, Cheung JW, Couvy-Duchesne B, Dale AM, Dalvie S, de Araujo TK, de Zubicaray GI, de Zwarte SMC, den Braber A, Doan NT, Dohm K, Ehrlich S, Engelbrecht HR, Erk S, Fan CC, Fedko IO, Foley SF, Ford JM, Fukunaga M, Garrett ME, Ge T, Giddaluru S, Goldman AL, Green MJ, Groenewold NA, Grotegerd D, Gurholt TP, Gutman BA, Hansell NK, Harris MA, Harrison MB, Haswell CC, Hauser M, Herms S, Heslenfeld DJ, Ho NF, Hoehn D, Hoffmann P, Holleran L, Hoogman M, Hottenga JJ, Ikeda M, Janowitz D, Jansen IE, Jia T, Jockwitz C, Kanai R, Karama S, Kasperaviciute D, Kaufmann T, Kelly S, Kikuchi M, Klein M, Knapp M, Knodt AR, Krämer B, Lam M, Lancaster TM, Lee PH, Lett TA, Lewis LB, Lopes-Cendes I, Luciano M, Macciardi F, Marquand AF, Mathias SR, Melzer TR, Milaneschi Y, Mirza-Schreiber N, Moreira JCV, Mühleisen TW, Müller-Myhsok B, Najt P, Nakahara S, Nho K, Olde Loohuis LM, Orfanos DP, Pearson JF, Pitcher TL, Pütz B, Quidé Y, Ragothaman A, Rashid FM, Reay WR, Redlich R, Reinbold CS, Repple J, Richard G, Riedel BC, Risacher SL, Rocha CS, Mota NR, Salminen L, Saremi A, Saykin AJ, Schlag F, Schmaal L, Schofield PR, Secolin R, Shapland CY, Shen L, Shin J, Shumskaya E, Sønderby IE, Sprooten E, Tansey KE, Teumer A, Thalamuthu A, Tordesillas-Gutiérrez D, Turner JA, Uhlmann A, Vallerga CL, van der Meer D, van Donkelaar MMJ, van Eijk L, van Erp TGM, van Haren NEM, van Rooij D, van Tol MJ, Veldink JH, Verhoef E, Walton E, Wang M, Wang Y, Wardlaw JM, Wen W, Westlye LT, Whelan CD, Witt SH, Wittfeld K, Wolf C, Wolfers T, Wu JQ, Yasuda CL, Zaremba D, Zhang Z, Zwiers MP, Artiges E, Assareh AA, Ayesa-Arriola R, Belger A, Brandt CL, Brown GG, Cichon S, Curran JE, Davies GE, Degenhardt F, Dennis MF, Dietsche B, Djurovic S, Doherty CP, Espiritu R, Garijo D, Gil Y, Gowland PA, Green RC, Häusler AN, Heindel W, Ho BC, Hoffmann WU, Holsboer F, Homuth G, Hosten N, Jack CR Jr, Jang M, Jansen A, Kimbrel NA, Kolskår K, Koops S, Krug A, Lim KO, Luykx JJ, Mathalon DH, Mather KA, Mattay VS, Matthews S, Mayoral Van Son J, McEwen SC, Melle I, Morris DW, Mueller BA, Nauck M, Nordvik JE, Nöthen MM, O'Leary DS, Opel N, Martinot MP, Pike GB, Preda A, Quinlan EB, Rasser PE, Ratnakar V, Reppermund S, Steen VM, Tooney PA, Torres FR, Veltman DJ, Voyvodic JT, Whelan R, White T, Yamamori H, Adams HHH, Bis JC, Debette S, Decarli C, Fornage M, Gudnason V, Hofer E, Ikram MA, Launer L, Longstreth WT, Lopez OL, Mazoyer B, Mosley TH, Roshchupkin GV, Satizabal CL, Schmidt R, Seshadri S, Yang Q; Alzheimer’s Disease Neuroimaging Initiative; CHARGE Consortium; EPIGEN Consortium; IMAGEN Consortium; SYS Consortium; Parkinson’s Progression Markers Initiative, Alvim MKM, Ames D, Anderson TJ, Andreassen OA, Arias-Vasquez A, Bastin ME, Baune BT, Beckham JC, Blangero J, Boomsma DI, Brodaty H, Brunner HG, Buckner RL, Buitelaar JK, Bustillo JR, Cahn W, Cairns MJ, Calhoun V, Carr VJ, Caseras X, Caspers S, Cavalleri GL, Cendes F, Corvin A, Crespo-Facorro B, Dalrymple-Alford JC, Dannlowski U, de Geus EJC, Deary IJ, Delanty N, Depondt C, Desrivières S, Donohoe G, Espeseth T, Fernández G, Fisher SE, Flor H, Forstner AJ, Francks C, Franke B, Glahn DC, Gollub RL, Grabe HJ, Gruber O, Håberg AK, Hariri AR, Hartman CA, Hashimoto R, Heinz A, Henskens FA, Hillegers MHJ, Hoekstra PJ, Holmes AJ, Hong LE, Hopkins WD, Hulshoff Pol HE, Jernigan TL, Jönsson EG, Kahn RS, Kennedy MA, Kircher TTJ, Kochunov P, Kwok JBJ, Le Hellard S, Loughland CM, Martin NG, Martinot JL, McDonald C, McMahon KL, Meyer-Lindenberg A, Michie PT, Morey RA, Mowry B, Nyberg L, Oosterlaan J, Ophoff RA, Pantelis C, Paus T, Pausova Z, Penninx BWJH, Polderman TJC, Posthuma D, Rietschel M, Roffman JL, Rowland LM, Sachdev PS, Sämann PG, Schall U, Schumann G, Scott RJ, Sim K, Sisodiya SM, Smoller JW, Sommer IE, St Pourcain B, Stein DJ, Toga AW, Trollor JN, Van der Wee NJA, van 't Ent D, Völzke H, Walter H, Weber B, Weinberger DR, Wright MJ, Zhou J, Stein JL, Thompson PM, Medland SE; Enhancing NeuroImaging Genetics through Meta-Analysis Consortium (ENIGMA)—Genetics working group. (2020). The genetic architecture of the human cerebral cortex. Science. 367(6484):eaay6690. doi: 10.1126/science.aay6690. PMID: 32193296

Bigdeli TB, Genovese G, Georgakopoulos P, Meyers JL, Peterson RE, Iyegbe CO, Medeiros H, Valderrama J, Achtyes ED, Kotov R, Stahl EA, Abbott C, Azevedo MH, Belliveau RA, Bevilacqua E, Bromet EJ, Byerley W, Carvalho CB, Chapman SB, DeLisi LE, Dumont AL, O'Dushlaine C, Evgrafov OV, Fochtmann LJ, Gage D, Kennedy JL, Kinkead B, Macedo A, Moran JL, Morley CP, Dewan MJ, Nemesh J, Perkins DO, Purcell SM, Rakofsky JJ, Scolnick EM, Sklar BM, Sklar P, Smoller JW, Sullivan PF, Macciardi F, Marder SR, Gur RC, Gur RE, Braff DL; Consortium on the Genetics of Schizophrenia (COGS) Investigators, Nicolini H, Escamilla MA, Vawter MP, Sobell JL, Malaspina D, Lehrer DS, Buckley PF, Rapaport MH, Knowles JA; Genomic Psychiatry Cohort (GPC) Consortium, Fanous AH, Pato MT, McCarroll SA, Pato CN. (2020). Contributions of common genetic variants to risk of schizophrenia among individuals of African and Latino ancestry. Mol Psychiatry. 25(10):2455-2467. doi: 10.1038/s41380-019-0517-y. PMID: 31591465

Nakahara S, Turner JA, Calhoun VD, Lim KO, Mueller B, Bustillo JR, O'Leary DS, McEwen S, Voyvodic J, Belger A, Mathalon DH, Ford JM, Macciardi F, Matsumoto M, Potkin SG, van Erp TGM. (2020). Dentate gyrus volume deficit in schizophrenia. Psychol Med. 50(8):1267-1277. doi: 10.1017/S0033291719001144. PMID: 31155012

Yu Q, Chen J, Du Y, Sui J, Damaraju E, Turner JA, van Erp TGM, Macciardi F, Belger A, Ford JM, McEwen S, Mathalon DH, Mueller BA, Preda A, Vaidya J, Pearlson GD, Calhoun VD. (2019). A method for building a genome-connectome bipartite graph model. J Neurosci Methods. 15;320:64-71. doi: 10.1016/j.jneumeth.2019.03.011. PMID: 30902651

Gunz P, Tilot AK, Wittfeld K, Teumer A, Shapland CY, van Erp TGM, Dannemann M, Vernot B, Neubauer S, Guadalupe T, Fernández G, Brunner HG, Enard W, Fallon J, Hosten N, Völker U, Profico A, Di Vincenzo F, Manzi G, Kelso J, St Pourcain B, Hublin JJ, Franke B, Pääbo S, Macciardi F, Grabe HJ, Fisher SE. (2019). Neandertal Introgression Sheds Light on Modern Human Endocranial Globularity. Curr Biol. 29(1):120-127.e5. doi: 10.1016/j.cub.2018.10.065

Guffanti G, Bartlett A, DeCrescenzo P, Macciardi F, Hunter R. (2019). Transposable Elements. Curr Top Behav Neurosci. doi: 10.1007/7854_2019_112.

Guffanti G, Bartlett A, Klengel T, Klengel C, Hunter R, Glinsky G, Macciardi F.: Novel Bioinformatics Approach Identifies Transcriptional Profiles of Lineage-Specific Transposable Elements at Distinct Loci in the Human Dorsolateral Prefrontal Cortex. Mol Biol Evol. 2018 35(10):2435-2453

van Erp TGM, Walton E, Hibar DP, Schmaal L, Jiang W, Glahn DC, Pearlson GD, Yao N, Fukunaga M, Hashimoto R, Okada N, Yamamori H, Bustillo JR, Clark VP, Agartz I, Mueller BA, Cahn W, de Zwarte SMC, Hulshoff Pol HE, Kahn RS, Ophoff RA, van Haren NEM, Andreassen OA, Dale AM, Doan NT, Gurholt TP, Hartberg CB, Haukvik UK, Jørgensen KN, Lagerberg TV, Melle I, Westlye LT, Gruber O, Kraemer B, Richter A, Zilles D, Calhoun VD, Crespo-Facorro B, Roiz-Santiañez R, Tordesillas-Gutiérrez D, Loughland C, Carr VJ, Catts S, Cropley VL, Fullerton JM, Green MJ, Henskens FA, Jablensky A, Lenroot RK, Mowry BJ, Michie PT, Pantelis C, Quidé Y, Schall U, Scott RJ, Cairns MJ, Seal M, Tooney PA, Rasser PE, Cooper G, Shannon Weickert C, Weickert TW, Morris DW, Hong E, Kochunov P, Beard LM, Gur RE, Gur RC, Satterthwaite TD, Wolf DH, Belger A, Brown GG, Ford JM, Macciardi F, Mathalon DH, O'Leary DS, Potkin SG, Preda A, Voyvodic J, Lim KO, McEwen S, Yang F, Tan Y, Tan S, Wang Z, Fan F, Chen J, Xiang H, Tang S, Guo H, Wan P, Wei D, Bockholt HJ, Ehrlich S, Wolthusen RPF, King MD, Shoemaker JM, Sponheim SR, De Haan L, Koenders L, Machielsen MW, van Amelsvoort T, Veltman DJ, Assogna F, Banaj N, de Rossi P, Iorio M, Piras F, Spalletta G, McKenna PJ, Pomarol-Clotet E, Salvador R, Corvin A, Donohoe G, Kelly S, Whelan CD, Dickie EW, Rotenberg D, Voineskos AN, Ciufolini S, Radua J, Dazzan P, Murray R, Reis Marques T, Simmons A, Borgwardt S, Egloff L, Harrisberger F, Riecher-Rössler A, Smieskova R, Alpert KI, Wang L, Jönsson EG, Koops S, Sommer IEC, Bertolino A, Bonvino A, Di Giorgio A, Neilson E, Mayer AR, Stephen JM, Kwon JS, Yun JY, Cannon DM, McDonald C, Lebedeva I, Tomyshev AS, Akhadov T, Kaleda V, Fatouros-Bergman H, Flyckt L; Karolinska Schizophrenia Project, Busatto GF, Rosa PGP, Serpa MH, Zanetti MV, Hoschl C, Skoch A, Spaniel F, Tomecek D, Hagenaars SP, McIntosh AM, Whalley HC, Lawrie SM, Knöchel C, Oertel-Knöchel V, Stäblein M, Howells FM, Stein DJ, Temmingh HS, Uhlmann A, Lopez-Jaramillo C, Dima D, McMahon A, Faskowitz JI, Gutman BA, Jahanshad N, Thompson PM, Turner JA. (2018). Cortical Brain Abnormalities in 4474 Individuals With Schizophrenia and 5098 Control Subjects via the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) Consortium. Biol Psychiatry. 84(9):644-654. doi:10.1016/j.biopsych.2018.04.023. PMID: 29960671

Gross T, Mapstone M, Miramontes R, Padilla R, Cheema AK, Macciardi F, Federoff HJ, Fiandaca MS (2018). Toward Reproducible Results from Targeted Metabolomic Studies: Perspectives for Data Pre-processing and a Basis for Analytic Pipeline Development. Curr Top Med Chem. 18(11):883-895. doi: 10.2174/1568026618666180711144323

van Erp TG, Hibar DP, Rasmussen JM, Glahn DC, Pearlson GD, Andreassen OA, Agartz I, Westlye LT, Haukvik UK, Dale AM, Melle I, Hartberg CB, Gruber O, Kraemer B, Zilles D, Donohoe G, Kelly S, McDonald C, Morris DW, Cannon DM, Corvin A, Machielsen MW, Koenders L, de Haan L, Veltman DJ, Satterthwaite TD, Wolf DH, Gur RC, Gur RE, Potkin SG, Mathalon DH, Mueller BA, Preda A, Macciardi F, Ehrlich S, Walton E, Hass J, Calhoun VD, Bockholt HJ, Sponheim SR, Shoemaker JM, van Haren NE, Pol HE, Ophoff RA, Kahn RS, Roiz-Santiañez R, Crespo-Facorro B, Wang L, Alpert KI, Jönsson EG, Dimitrova R, Bois C, Whalley HC, McIntosh AM, Lawrie SM, Hashimoto R, Thompson PM, Turner JA.: Subcortical brain volume abnormalities in 2028 individuals with schizophrenia and 2540 healthy controls via the ENIGMA consortium. Mol Psychiatry. 2015 doi: 10.1038/mp.2015.63

Brami-Cherrier K, Anzalone A, Ramos M, Forne I, Macciardi F, Imhof A, Borrelli E.: Epigenetic reprogramming of cortical neurons through alteration of dopaminergic circuits. Mol Psychiatry. 2014 doi: 10.1038/mp.2014.67

Guffanti G, Gaudi S, Fallon JH, Sobell J, Potkin SG, Pato C, Macciardi F: Transposable elements and psychiatric disorders. Am J Med Genet B Neuropsychiatr Genet. 2014 165B(3):201-16. doi: 10.1002/ajmg.b.32225

Guella I, Sequeira A, Rollins B, Morgan L, Torri F, van Erp TG, Myers RM, Barchas JD, Schatzberg AF, Watson SJ, Akil H, Bunney WE, Potkin SG, Macciardi F, Vawter MP: Analysis of miR-137 expression and rs1625579 in dorsolateral prefrontal cortex.  Psychiatr Res. 2013. doi:10.1016/j.jpsychires.2013.05.021

van Erp TG, Guella I, Vawter MP, Turner J, Brown GG, McCarthy G, Greve DN, Glover GH, Calhoun VD, Lim KO, Bustillo JR, Belger A, Ford JM, Mathalon DH, Diaz M, Preda A, Nguyen D, Macciardi F, Potkin SG.: Schizophrenia miR-137 Locus Risk Genotype is Associated with Dorsolateral Prefrontal Cortex Hyperactivation. Biol Psychiatry. 2013 Aug doi: 10.1016/j.biopsych.2013.06.016

Balestrieri E, Arpino C, Matteucci C, Sorrentino R, Pica F, Alessandrelli R, Coniglio A, Curatolo P, Rezza G, Macciardi F, Garaci E, Gaudi S, Sinibaldi-Vallebona P: HERVs Expression in Autism Spectrum Disorders. PLoS One 2012;7(11):e48831. doi: 10.1371/journal.pone.0048831

Torri F., Dinov I.D., Zamanyan A., Hobel S., Genco A., Petrosyan P., Clark A.P., Liu Z., Eggert P., Pierce J., Knowles J.A., Ames J., Kesselman C., Toga A.W., Potkin S.G., Vawter M.P., Macciardi F. Next Generation Sequence Analysis and Computational Genomics Using Graphical Pipeline Workflows. Genes. 2012; 3(3):545-575

Potkin SG, Macciardi F, Guffanti G, Fallon JH, Wang Q, Turner JA, Lakatos A, Miles MF, Lander A, Vawter MP, Xie XH. 2010. Identifying gene regulatory networks in schizophrenia. Neuroimage. 53:839-847. DOI: 10.1016/j.neuroimage.2010.06.036

Torri F, Akelai A, Lupoli S, Sironi M, Amann-Zalcenstein D, Fumagalli M, Ben-Asher E, Kanyas K, Cagliani R, Cozzi P, Trombetti G, Strik Lievers L, Salvi E, Orro A, Beckmann JS, Lancet D, Kohn Y, Milanesi L, Ebstein RB, Lerer B, Macciardi F. 2010. Fine Mapping of AHI1 as a Schizophrenia Susceptibility Gene: from Association to Evolutionary Evidence. FASEB Journal. 24:3066-82. DOI: 10.1096/fj.09-152611

Potkin SG, Turner JA, Guffanti G, Lakatos A, Fallon JH, Nguyen DD, Mathalon D, Ford J, Lauriello J, Macciardi F. 2009. FBIRN: A genome-wide association study of schizophrenia using brain activation as a quantitative phenotype. Schizophrenia Bulletin. 35:96-108. DOI: 10.1093/schbul/sbn155

1 R21 MH115327-01 (MPI: G. Guffanti – F. Macciardi) 09/01/2017 – 08/31/2021 The role of Human Endogenous Retroviruses (HERVs) in the regulation of neural genome of schizophrenia The goal of the proposed research is to study how brain expressed Human Endogenous Retroviruses (HERVs) regulate gene-networks and represent a potential risk factor in developing schizophrenia. The main hypothesis, is that HERVs play a critical role in dys-regulating the expression of many genes in schizophrenia, ultimately altering regulatory neural circuitry functions. Role: MPI

1 R01 AG058644-01 09/01/2018 – 08/31/2022 Multi-omic Investigation of Exercise Effects in Mild Cognitive Impairment This project will measure metabolomic and proteomic markers obtained from blood in a group of 350 older adults participating in the NIA-funded, ADCS EXERT study, an aerobic exercise intervention for MCI. We will integrate metabolomic and proteomic elements creating a biomarker of exercise in MCI. Role: co-Investigator (P.I.: M. Mapstone)

1 U19 AG 068054-01 (Handen/Christian/Head/Mapstone) 09/01/20 - 08/31/25 NIH/NIA: Alzheimer's Biomarker Consortium - Down Syndrome (ABC - DS) To test hypotheses related to how AD in DS may parallel sporadic AD within an amyloid, tau, neurodegeneration AT(N) framework and to identify modifiers of risk of conversion/progression. Role: co-Investigator

American Society of Human Genetics (ASHG)

American Association of Physical Anthropologists (AAPA)

Director of the Department of Genetic Epidemiology and Biostatistics
Genset SA, Paris, France 2002—2005

Joanne Murphy Endowed Chair in Behavioral Neuroscience
University of Toronto, Canada 2001—2005

Associate Professor, Medical Genetics
University of Milano (Italy) 2001—2010

Psychiatry/Neurology

Center for Epigenetics and Metabolism - School of Medicine (joint with BioSci)

Center for Autism Research and Treatment (CART)

Center for Complex Biological Systems

Link to this profile
https://faculty.uci.edu/profile/?facultyId=5893

Last updated
11/10/2021