Nadav Ahituv, PhD

Professor
Department of Bioengineering and Therapeutic Sciences
[email protected]
+1 415 476-1838

The Ahituv lab is focused on understanding the role of regulatory sequences in human biology and disease. Through a combination of comparative genomic strategies, biochemical assays, regulatory element analysis, human patient samples, mouse and fish genetic engineering technologies, and massively parallel reporter assays they are working to elucidate mechanisms whereby genetic variation within these sequences lead to changes in human phenotypes.

Research Summary: 
Gene regulation and human disease

Websites

Publications: 

A Genome-wide Framework for Mapping Gene Regulation via Cellular Genetic Screens.

Cell

Gasperini M, Hill AJ, McFaline-Figueroa JL, Martin B, Kim S, Zhang MD, Jackson D, Leith A, Schreiber J, Noble WS, Trapnell C, Ahituv N, Shendure J

Reply to Liu et al.: Tissue specificity of SIM1 gene expression and erectile dysfunction.

Proceedings of the National Academy of Sciences of the United States of America

Jorgenson E, Matharu N, Palmer MR, Yin J, Shan J, Hoffmann TJ, Thai KK, Zhou X, Hotaling JM, Jarvik GP, Ahituv N, Wessells H, Van Den Eeden SK

A Genome-wide Framework for Mapping Gene Regulation via Cellular Genetic Screens.

Cell

Gasperini M, Hill AJ, McFaline-Figueroa JL, Martin B, Kim S, Zhang MD, Jackson D, Leith A, Schreiber J, Noble WS, Trapnell C, Ahituv N, Shendure J

Genome-wide de novo risk score implicates promoter variation in autism spectrum disorder.

Science (New York, N.Y.)

An JY, Lin K, Zhu L, Werling DM, Dong S, Brand H, Wang HZ, Zhao X, Schwartz GB, Collins RL, Currall BB, Dastmalchi C, Dea J, Duhn C, Gilson MC, Klei L, Liang L, Markenscoff-Papadimitriou E, Pochareddy S, Ahituv N, Buxbaum JD, Coon H, Daly MJ, Kim YS, Marth GT, Neale BM, Quinlan AR, Rubenstein JL, Sestan N, State MW, Willsey AJ, Talkowski ME, Devlin B, Roeder K, Sanders SJ

CRISPR-mediated activation of a promoter or enhancer rescues obesity caused by haploinsufficiency.

Science (New York, N.Y.)

Matharu N, Rattanasopha S, Tamura S, Maliskova L, Wang Y, Bernard A, Hardin A, Eckalbar WL, Vaisse C, Ahituv N

Genome-wide meta-analysis and replication studies in multiple ethnicities identify novel adolescent idiopathic scoliosis susceptibility loci.

Human molecular genetics

Khanshour AM, Kou I, Fan Y, Einarsdottir E, Makki N, Kidane YH, Kere J, Grauers A, Johnson TA, Paria N, Patel C, Singhania R, Kamiya N, Takeda K, Otomo N, Watanabe K, Luk KDK, Cheung KMC, Herring JA, Rios JJ, Ahituv N, Gerdhem P, Gurnett CA, Song YQ, Ikegawa S, Wise CA

A multidisciplinary review of triphalangeal thumb.

The Journal of hand surgery, European volume

Potuijt JWP, Galjaard RH, van der Spek PJ, van Nieuwenhoven CA, Ahituv N, Oberg KC, Hovius SER

Genetic variation in the SIM1 locus is associated with erectile dysfunction.

Proceedings of the National Academy of Sciences of the United States of America

Jorgenson E, Matharu N, Palmer MR, Yin J, Shan J, Hoffmann TJ, Thai KK, Zhou X, Hotaling JM, Jarvik GP, Ahituv N, Wessells H, Van Den Eeden SK

Whole Genome Sequencing of Pharmacogenetic Drug Response in Racially Diverse Children with Asthma.

American journal of respiratory and critical care medicine

Mak AC, White MJ, Eckalbar WL, Szpiech ZA, Oh SS, Pino-Yanes M, Hu D, Goddard P, Huntsman S, Galanter J, Wu AC, Himes BE, Germer S, Vogel JM, Bunting KL, Eng C, Salazar S, Keys KL, Liberto J, Nuckton TJ, Nguyen TA, Torgerson DG, Kwok PY, Levin AM, Celedón JC, Forno E, Hakonarson H, Sleiman PM, Dahlin A, Tantisira KG, Weiss ST, Serebrisky D, Brigino-Buenaventura E, Farber HJ, Meade K, Lenoir MA, Avila PC, Sen S, Thyne SM, Rodriguez-Cintron W, Winkler CA, Moreno-Estrada A, Sandoval K, Rodriguez-Santana JR, Kumar R, Williams LK, Ahituv N, Ziv E, Seibold MA, Darnell RB, Zaitlen N, Hernandez RD, Burchard EG

Corrigendum: A systematic comparison reveals substantial differences in chromosomal versus episomal encoding of enhancer activity.

Genome research

Inoue F, Kircher M, Martin B, Cooper GM, Witten DM, McManus MT, Ahituv N, Shendure J

A point mutation in the pre-ZRS disrupts sonic hedgehog expression in the limb bud and results in triphalangeal thumb-polysyndactyly syndrome.

Genetics in medicine : official journal of the American College of Medical Genetics

Potuijt JWP, Baas M, Sukenik-Halevy R, Douben H, Nguyen P, Venter DJ, Gallagher R, Swagemakers SM, Hovius SER, van Nieuwenhoven CA, Galjaard RH, van der Spek PJ, Ahituv N, de Klein A

Rare Variants in the ABCG2 Promoter Modulate In Vivo Activity.

Drug metabolism and disposition: the biological fate of chemicals

Eclov RJ, Kim MJ, Smith R, Ahituv N, Kroetz DL

ABCG2 regulatory single-nucleotide polymorphisms alter in vivo enhancer activity and expression.

Pharmacogenetics and genomics

Eclov RJ, Kim MJ, Chhibber A, Smith RP, Ahituv N, Kroetz DL

CRISPR-Cas9-mediated functional dissection of 3'-UTRs.

Nucleic acids research

Zhao W, Siegel D, Biton A, Tonqueze OL, Zaitlen N, Ahituv N, Erle DJ

Variant Interpretation: Functional Assays to the Rescue.

American journal of human genetics

Starita LM, Ahituv N, Dunham MJ, Kitzman JO, Roth FP, Seelig G, Shendure J, Fowler DM

Gene Regulatory Elements, Major Drivers of Human Disease.

Annual review of genomics and human genetics

Chatterjee S, Ahituv N

Limb development: a paradigm of gene regulation.

Nature reviews. Genetics

Petit F, Sears KE, Ahituv N

Genomic Characterization of Metformin Hepatic Response.

PLoS genetics

Luizon MR, Eckalbar WL, Wang Y, Jones SL, Smith RP, Laurance M, Lin L, Gallins PJ, Etheridge AS, Wright F, Zhou Y, Molony C, Innocenti F, Yee SW, Giacomini KM, Ahituv N

In Vivo Hepatic Enhancer Elements in the Human ABCG2 Locus.

Drug metabolism and disposition: the biological fate of chemicals

Eclov RJ, Kim MJ, Smith RP, Liang X, Ahituv N, Kroetz DL

A systematic comparison reveals substantial differences in chromosomal versus episomal encoding of enhancer activity.

Genome research

Inoue F, Kircher M, Martin B, Cooper GM, Witten DM, McManus MT, Ahituv N, Shendure J

Bat Accelerated Regions Identify a Bat Forelimb Specific Enhancer in the HoxD Locus.

PLoS genetics

Booker BM, Friedrich T, Mason MK, VanderMeer JE, Zhao J, Eckalbar WL, Logan M, Illing N, Pollard KS, Ahituv N

Transcriptomic and epigenomic characterization of the developing bat wing.

Nature genetics

Eckalbar WL, Schlebusch SA, Mason MK, Gill Z, Parker AV, Booker BM, Nishizaki S, Muswamba-Nday C, Terhune E, Nevonen KA, Makki N, Friedrich T, VanderMeer JE, Pollard KS, Carbone L, Wall JD, Illing N, Ahituv N

Prenatal ß-catenin/Brn2/Tbr2 transcriptional cascade regulates adult social and stereotypic behaviors.

Molecular psychiatry

Belinson H, Nakatani J, Babineau BA, Birnbaum RY, Ellegood J, Bershteyn M, McEvilly RJ, Long JM, Willert K, Klein OD, Ahituv N, Lerch JP, Rosenfeld MG, Wynshaw-Boris A

A genome-wide association study identifies four novel susceptibility loci underlying inguinal hernia.

Nature communications

Jorgenson E, Makki N, Shen L, Chen DC, Tian C, Eckalbar WL, Hinds D, Ahituv N, Avins A

Uncovering drug-responsive regulatory elements.

Pharmacogenomics

Luizon MR, Ahituv N

Functionally conserved enhancers with divergent sequences in distant vertebrates.

BMC genomics

Yang S, Oksenberg N, Takayama S, Heo SJ, Poliakov A, Ahituv N, Dubchak I, Boffelli D

Identification of novel Fgf enhancers and their role in dental evolution.

Evolution & development

Tapaltsyan V, Charles C, Hu J, Mindell D, Ahituv N, Wilson GM, Black BL, Viriot L, Klein OD

A PAX1 enhancer locus is associated with susceptibility to idiopathic scoliosis in females.

Nature communications

Sharma S, Londono D, Eckalbar WL, Gao X, Zhang D, Mauldin K, Kou I, Takahashi A, Matsumoto M, Kamiya N, Murphy KK, Cornelia R

Enhancer interaction networks as a means for singular olfactory receptor expression.

Cell

Markenscoff-Papadimitriou E, Allen WE, Colquitt BM, Goh T, Murphy KK, Monahan K, Mosley CP, Ahituv N, Lomvardas S

Systematic dissection of coding exons at single nucleotide resolution supports an additional role in cell-specific transcriptional regulation.

PLoS genetics

Birnbaum RY, Patwardhan RP, Kim MJ, Findlay GM, Martin B, Zhao J, Bell RJ, Smith RP, Ku AA, Shendure J, Ahituv N

Genome-wide discovery of drug-dependent human liver regulatory elements.

PLoS genetics

Smith RP, Eckalbar WL, Morrissey KM, Luizon MR, Hoffmann TJ, Sun X, Jones SL, Force Aldred S, Ramamoorthy A, Desta Z, Liu Y, Skaar TC, Trinklein ND, Giacomini KM, Ahituv N

Genome-wide identification of signaling center enhancers in the developing limb.

Development (Cambridge, England)

VanderMeer JE, Smith RP, Jones SL, Ahituv N

Genome-wide distribution of Auts2 binding localizes with active neurodevelopmental genes.

Translational psychiatry

Oksenberg N, Haliburton GD, Eckalbar WL, Oren I, Nishizaki S, Murphy K, Pollard KS, Birnbaum RY, Ahituv N

Integrating diverse datasets improves developmental enhancer prediction.

PLoS computational biology

Erwin GD, Oksenberg N, Truty RM, Kostka D, Murphy KK, Ahituv N, Pollard KS, Capra JA

A novel ZRS mutation leads to preaxial polydactyly type 2 in a heterozygous form and Werner mesomelic syndrome in a homozygous form.

Human mutation

VanderMeer JE, Lozano R, Sun M, Xue Y, Daentl D, Jabs EW, Wilcox WR, Ahituv N

Identification of three novel FGF16 mutations in X-linked recessive fusion of the fourth and fifth metacarpals and possible correlation with heart disease.

Molecular genetics & genomic medicine

Laurell T, Nilsson D, Hofmeister W, Lindstrand A, Ahituv N, Vandermeer J, Amilon A, Annerén G, Arner M, Pettersson M, Jäntti N, Rosberg HE, Cattini PA, Nordenskjöld A, Mäkitie O, Grigelioniene G, Nordgren A

Genetic association study of adiposity and melanocortin-4 receptor (MC4R) common variants: replication and functional characterization of non-coding regions.

PloS one

Evans DS, Calton MA, Kim MJ, Kwok PY, Miljkovic I, Harris T, Koster A, Liu Y, Tranah GJ, Ahituv N, Hsueh WC, Vaisse C

Chromatin connectivity maps reveal dynamic promoter-enhancer long-range associations.

Nature

Zhang Y, Wong CH, Birnbaum RY, Li G, Favaro R, Ngan CY, Lim J, Tai E, Poh HM, Wong E, Mulawadi FH, Sung WK, Nicolis S, Ahituv N, Ruan Y, Wei CL

Functional characterization of SIM1-associated enhancers.

Human molecular genetics

Kim MJ, Oksenberg N, Hoffmann TJ, Vaisse C, Ahituv N

Functional analysis of limb enhancers in the developing fin.

Development genes and evolution

Booker BM, Murphy KK, Ahituv N

The role of AUTS2 in neurodevelopment and human evolution.

Trends in genetics : TIG

Oksenberg N, Ahituv N

Massively parallel decoding of mammalian regulatory sequences supports a flexible organizational model.

Nature genetics

Smith RP, Taher L, Patwardhan RP, Kim MJ, Inoue F, Shendure J, Ovcharenko I, Ahituv N

A compact, in vivo screen of all 6-mers reveals drivers of tissue-specific expression and guides synthetic regulatory element design.

Genome biology

Smith RP, Riesenfeld SJ, Holloway AK, Li Q, Murphy KK, Feliciano NM, Orecchia L, Oksenberg N, Pollard KS, Ahituv N

Function and regulation of AUTS2, a gene implicated in autism and human evolution.

PLoS genetics

Oksenberg N, Stevison L, Wall JD, Ahituv N

Sequence signatures extracted from proximal promoters can be used to predict distal enhancers.

Genome biology

Taher L, Smith RP, Kim MJ, Ahituv N, Ovcharenko I

The hydrodynamic tail vein assay as a tool for the study of liver promoters and enhancers.

Methods in molecular biology (Clifton, N.J.)

Kim MJ, Ahituv N

Mutations in DMRT3 affect locomotion in horses and spinal circuit function in mice.

Nature

Andersson LS, Larhammar M, Memic F, Wootz H, Schwochow D, Rubin CJ, Patra K, Arnason T, Wellbring L, Hjälm G, Imsland F, Petersen JL, McCue ME, Mickelson JR, Cothran G, Ahituv N, Roepstorff L, Mikko S, Vallstedt A, Lindgren G, Andersson L, Kullander K

Functional characterization of tissue-specific enhancers in the DLX5/6 locus.

Human molecular genetics

Birnbaum RY, Everman DB, Murphy KK, Gurrieri F, Schwartz CE, Ahituv N

Human developmental enhancers conserved between deuterostomes and protostomes.

PLoS genetics

Clarke SL, VanderMeer JE, Wenger AM, Schaar BT, Ahituv N, Bejerano G

A novel ZRS mutation in a Balochi tribal family with triphalangeal thumb, pre-axial polydactyly, post-axial polydactyly, and syndactyly.

American journal of medical genetics. Part A

VanderMeer JE, Afzal M, Alyas S, Haque S, Ahituv N, Malik S

Studies of TBX4 and chromosome 17q23.1q23.2: an uncommon cause of nonsyndromic clubfoot.

American journal of medical genetics. Part A

Lu W, Bacino CA, Richards BS, Alvarez C, VanderMeer JE, Vella M, Ahituv N, Sikka N, Dietz FR, Blanton SH, Hecht JT

Pharmacogene regulatory elements: from discovery to applications.

Genome medicine

Smith RP, Lam ET, Markova S, Yee SW, Ahituv N

A novel 13 base pair insertion in the sonic hedgehog ZRS limb enhancer (ZRS/LMBR1) causes preaxial polydactyly with triphalangeal thumb.

Human mutation

Laurell T, Vandermeer JE, Wenger AM, Grigelioniene G, Nordenskjöld A, Arner M, Ekblom AG, Bejerano G, Ahituv N, Nordgren A

Coding exons function as tissue-specific enhancers of nearby genes.

Genome research

Birnbaum RY, Clowney EJ, Agamy O, Kim MJ, Zhao J, Yamanaka T, Pappalardo Z, Clarke SL, Wenger AM, Nguyen L, Gurrieri F, Everman DB, Schwartz CE, Birk OS, Bejerano G, Lomvardas S, Ahituv N

Massively parallel functional dissection of mammalian enhancers in vivo.

Nature biotechnology

Patwardhan RP, Hiatt JB, Witten DM, Kim MJ, Smith RP, May D, Lee C, Andrie JM, Lee SI, Cooper GM, Ahituv N, Pennacchio LA, Shendure J

Location, location, cis-mutation.

Human mutation

Ahituv N

Functional characterization of liver enhancers that regulate drug-associated transporters.

Clinical pharmacology and therapeutics

Kim MJ, Skewes-Cox P, Fukushima H, Hesselson S, Yee SW, Ramsey LB, Nguyen L, Eshragh JL, Castro RA, Wen CC, Stryke D, Johns SJ, Ferrin TE, Kwok PY, Relling MV, Giacomini KM, Kroetz DL, Ahituv N

cis-regulatory mutations are a genetic cause of human limb malformations.

Developmental dynamics : an official publication of the American Association of Anatomists

VanderMeer JE, Ahituv N

Identification and characterization of novel polymorphisms in the basal promoter of the human transporter, MATE1.

Pharmacogenetics and genomics

Ha Choi J, Wah Yee S, Kim MJ, Nguyen L, Ho Lee J, Kang JO, Hesselson S, Castro RA, Stryke D, Johns SJ, Kwok PY, Ferrin TE, Goo Lee M, Black BL, Ahituv N, Giacomini KM

Identification and characterization of proximal promoter polymorphisms in the human concentrative nucleoside transporter 2 (SLC28A2).

The Journal of pharmacology and experimental therapeutics

Yee SW, Shima JE, Hesselson S, Nguyen L, De Val S, Lafond RJ, Kawamoto M, Johns SJ, Stryke D, Kwok PY, Ferrin TE, Black BL, Gurwitz D, Ahituv N, Giacomini KM

Association of functionally significant Melanocortin-4 but not Melanocortin-3 receptor mutations with severe adult obesity in a large North American case-control study.

Human molecular genetics

Calton MA, Ersoy BA, Zhang S, Kane JP, Malloy MJ, Pullinger CR, Bromberg Y, Pennacchio LA, Dent R, McPherson R, Ahituv N, Vaisse C

A new mouse mutant for the LDL receptor identified using ENU mutagenesis.

Journal of lipid research

Svenson KL, Ahituv N, Durgin RS, Savage H, Magnani PA, Foreman O, Paigen B, Peters LL

Alternative approach to a heavy weight problem.

Genome research

Goren A, Kim E, Amit M, Bochner R, Lev-Maor G, Ahituv N, Ast G

In vivo characterization of human APOA5 haplotypes.

Genomics

Ahituv N, Akiyama J, Chapman-Helleboid A, Fruchart J, Pennacchio LA

Gain-of-function R225W mutation in human AMPKgamma(3) causing increased glycogen and decreased triglyceride in skeletal muscle.

PloS one

Costford SR, Kavaslar N, Ahituv N, Chaudhry SN, Schackwitz WS, Dent R, Pennacchio LA, McPherson R, Harper ME

Deletion of ultraconserved elements yields viable mice.

PLoS biology

Ahituv N, Zhu Y, Visel A, Holt A, Afzal V, Pennacchio LA, Rubin EM

Medical sequencing at the extremes of human body mass.

American journal of human genetics

Ahituv N, Kavaslar N, Schackwitz W, Ustaszewska A, Martin J, Hebert S, Doelle H, Ersoy B, Kryukov G, Schmidt S, Yosef N, Ruppin E, Sharan R, Vaisse C, Sunyaev S, Dent R, Cohen J, McPherson R, Pennacchio LA

In vivo enhancer analysis of human conserved non-coding sequences.

Nature

Pennacchio LA, Ahituv N, Moses AM, Prabhakar S, Nobrega MA, Shoukry M, Minovitsky S, Dubchak I, Holt A, Lewis KD, Plajzer-Frick I, Akiyama J, De Val S, Afzal V, Black BL, Couronne O, Eisen MB, Visel A, Rubin EM

A distal enhancer and an ultraconserved exon are derived from a novel retroposon.

Nature

Bejerano G, Lowe CB, Ahituv N, King B, Siepel A, Salama SR, Rubin EM, Kent WJ, Haussler D

A PYY Q62P variant linked to human obesity.

Human molecular genetics

Ahituv N, Kavaslar N, Schackwitz W, Ustaszewska A, Collier JM, Hébert S, Doelle H, Dent R, Pennacchio LA, McPherson R

Mapping cis-regulatory domains in the human genome using multi-species conservation of synteny.

Human molecular genetics

Ahituv N, Prabhakar S, Poulin F, Rubin EM, Couronne O

Comparative genomic analysis reveals a distant liver enhancer upstream of the COUP-TFII gene.

Mammalian genome : official journal of the International Mammalian Genome Society

Baroukh N, Ahituv N, Chang J, Shoukry M, Afzal V, Rubin EM, Pennacchio LA

Exploiting human--fish genome comparisons for deciphering gene regulation.

Human molecular genetics

Ahituv N, Rubin EM, Nobrega MA

An ENU-induced mutation in AP-2alpha leads to middle ear and ocular defects in Doarad mice.

Mammalian genome : official journal of the International Mammalian Genome Society

Ahituv N, Erven A, Fuchs H, Guy K, Ashery-Padan R, Williams T, de Angelis MH, Avraham KB, Steel KP

Mouse models for human deafness: current tools for new fashions.

Trends in molecular medicine

Ahituv N, Avraham KB

MYO6, the human homologue of the gene responsible for deafness in Snell's waltzer mice, is mutated in autosomal dominant nonsyndromic hearing loss.

American journal of human genetics

Melchionda S, Ahituv N, Bisceglia L, Sobe T, Glaser F, Rabionet R, Arbones ML, Notarangelo A, Di Iorio E, Carella M, Zelante L, Estivill X, Avraham KB, Gasparini P

The Notch ligand Jagged1 is required for inner ear sensory development.

Proceedings of the National Academy of Sciences of the United States of America

Kiernan AE, Ahituv N, Fuchs H, Balling R, Avraham KB, Steel KP, Hrabé de Angelis M

Genomic structure of the human unconventional myosin VI gene.

Gene

Ahituv N, Sobe T, Robertson NG, Morton CC, Taggart RT, Avraham KB

Auditory and vestibular mouse mutants: models for human deafness.

Journal of basic and clinical physiology and pharmacology

Ahituv N, Avraham KB

Mutation in transcription factor POU4F3 associated with inherited progressive hearing loss in humans.

Science (New York, N.Y.)

Vahava O, Morell R, Lynch ED, Weiss S, Kagan ME, Ahituv N, Morrow JE, Lee MK, Skvorak AB, Morton CC, Blumenfeld A, Frydman M, Friedman TB, King MC, Avraham KB