Irfan Saadi, Ph.D.

Assistant Professor
Dept. of Anatomy and Cell Biology
Member, Center for Epigenetics and Stem Cell Biology

Ph.D., The University of Iowa, 2003
Postdoctoral, Brigham and Women's Hospital, Harvard Medical School, 2003-2009
Postdoctoral, The Forsyth Institute, Cambridge, MA, 2009-2011


SPECC1L deficiency leads to facial malformations.  (a) Tessier IV type cleft in the patient with SPECC1L Q415P mutation. (b) Whole-mount in situ hybridization shows Specc1l expression in maxillary and lateral nasal prominences (bracket), eyes (arrow), and limbs (arrowhead).  (c) Lateral view of fish stained for cartilage. (d) Specc1l morphant results in a 'faceless' phenotype lacking facial structures (arrows and brackets).

The focus of my research is to understand the pathogenetic mechanisms of craniofacial birth defects.  Craniofacial malformations afflict about 5% of all infants born in the United States and comprise approximately one third of all birth defects. These anomalies result in significant medical, social and economic consequences. Orofacial clefts are one such common congenital facial defect that affects 1/800 live births. Cleft lip with or without cleft palate (CL/P) comprises the majority of orofacial clefts. The Center for Disease Control and Prevention (CDC) estimates that the lifetime cost for treating kids born each year with CL/P is over US$697 million.  We have identified mutations in a novel cytoskeletal gene, SPECC1L, in patients with a severe manifestation of facial clefts that extend from the oral cavity to the eye - called oblique facial clefts (ObFC).  Although less common, insights into the cellular and molecular mechanisms underlying ObFC will directly impact our understanding of more common facial malformations, including cleft lip and hemifacial microsomia.

Selected Publications

Saadi I, Smina EV, Amendt BA, Harris D, Murphy KP, Murray JC, Russo AF (2001) Identification of a dominant negative homeodomain mutation in Rieger syndrome.  Journal of Biological Chemistry 276:23034-23041.

Saadi I, Kuburas A, Engle JJ, Russo AF (2003) Dominant-negative dimerization of a mutant homeodomain protein in Axenfeld-Rieger syndrome.  Molecular and Cellular Biology 23:1968-1982.

Toro R*, Saadi I*, Kuburas A, Russo AF (2004) Cell specific activation of the ANF promoter by PITX2 and MEF2A.  Journal of Biological Chemistry 279:52087-94. (*Co-First Authors)

Saadi I*, Toro R*, Kuburas A, Semina EV, Murray JC, Russo AF (2006) An Unusual Class of PITX2 Mutations in Axenfeld-Rieger Syndrome.  Birth Defects Research A: Clinical and Molecular Teratology 76:175-81. (*Co-First Authors)

Alkuraya FS*, Saadi I*, Lund JJ, Turbe-Doan A, Morton CC, Maas RL (2006) SUMO1 haploinsufficiency leads to cleft lip and palate.  Science 313:1751. (*Co-First Authors)

Higgins AW, Alkuraya FS, Bosco AF, Bruns GAP, Donovan DJ, Eisenman R, Farra CG, Ferguson HL, Gusella JF, Harris DJ, Herrick SR, Kelly C, Kim HG, Kocher KM, Korf BR, Kulkarni S, Leach NT, Lemyre E, Lewis J, Ligon AH, Lu W, Maas RL, MacDonald ME, Moore SD, Peters RE, Quade BJ, Quintero-Rivera F, Saadi I, Shen Y, Williamson RE, Morton CC (2008) Characterization of Apparently Balanced Chromosomal Rearrangements from the Developmental Genome Anatomy Project.  American Journal of Human Genetics 82:712-22.

Wang XP, O'Connell DJ, Lund JJ, Saadi I, Kuraguchi M, Turbe-Doan A, Cavallesco R, Kim H, Park PJ, Harada H, Kucherlapati R, Maas RL (2009) Apc inhibition of Wnt signaling regulates supernumerary tooth formation throughout embryogenesis and adulthood.  Development 136:1939-49.

Lachke SA, Alkuraya FS, Kneeland S, Ohn T, Aboukhalil A, Howell G, Saadi I, Cavallesco R, Yingzi Y, Tsai AC, Nair SK, Cosma MI, Smith RS, Hodges E, AlFadhli SM, Al-Hajeri A, Shamseddin H, Behbehani A, Hannon G, Bulyk ML, Drack AV, Anderson PJ, John SW, Maas RL (2011) Mutations in the RNA granule component TDRD7 cause cataract and glaucoma.  Science 331:1571-1576. 

Saadi I*, Alkuraya FS*, Gisselbrecht S, Goessling W, Cavallesco R, Turbe-Doan A, Petrin AL, Harris J, Siddiqui U, Grix AW, Hove HD, Leboulch P, Glover TW, Morton CC, Richieri-Costa A, Murray JC, Erickson R, Maas RL (2011) Deficiency of the Cytoskeletal Protein SPECC1L Leads to Oblique Facial Clefting.  American Journal of Human Genetics 89:44-55.  (*Co-First Authors)

Last modified: Feb 24, 2014

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Irfan Saadi, Ph.D.
Assistant Professor
Dept. of Anatomy and Cell Biology

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