Irfan Saadi, PhD

Assistant Professor
Anatomy and Cell Biology
Kansas Intellectual and Developmental Disabilities Research Center

PhD: 2003, The University of Iowa, Iowa City, IA
Postdoctoral Fellow: Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
Postdoctoral Fellow: The Forsyth Institute, Cambridge, MA


Publications:PubMed

Research

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.

THM1 (green) localizes in a punctate fashion from base to tip of cilium.  Tubulin (red) marks the ciliary core or axoneme.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).

SPECC1L deficiency in zebrafish, Drosophila, and mammalian cells shows a role for SPECC1L in cell migration and adhesion, downstream of the integrin, Ca2+ and non-canonical Wnt signaling pathways, each of which engenders reorganization of the actin cytoskeleton.  The knockdown in zebrafish specifically implicates impaired cranial neural crest (CNC) cell migration to the embryonic branchial arches that give rise to the developing facial prominences.  Collectively, these data begin to provide - for the first time - a genetic basis for ObFC and implicate defective SPECC1L-mediated cell migration and adhesion as a potential underlying mechanism.  We are currently using cellular and molecular analyses to elucidate SPECCIL function in cell adhesion and migration and to identify affected signaling pathways and the protein interactors involved. SPECC1L physical interactors will help to further visualize the function of SPECC1L as a "cross-linker" between the microtubule and actin cytoskeletons, as well as its potential role in cell polarity, directional cell division, and motility.

Specc1l-GFP stabilizes microtubules and distorts actin cytoskeletonSpecc1l-GFP stabilizes microtubules and distorts actin cytoskeleton.

Actin cytoskeleton reorganization defects in SPECC1L knockdown cellsActin cytoskeleton reorganization defects in SPECC1L knockdown cells.

Additionally, we are collaborating with Dr. Majed Dasouki (Dept. of Pediatrics, KUMC) and Dr. Brian Andrews (Dept. of Plastic Surgery, KUMC) to identify novel genes and pathways impaired in patients with orofacial birth defects. Together, this knowledge will provide mechanistic insights into the pathogenesis of ObFC and of other related craniofacial malformations.

Our Lab

Left to right: Adam Olm-Shipman (Lab Manager), Irfan Saadi, PhD (PI), Syed Rafi, PhD (Senior Scientist).

Last modified: Apr 15, 2014

Irfan Saadi, PhD

Contact

Irfan Saadi, PhD
Assistant Professor
Anatomy and Cell Biology

HSLIC Room 2065, Mailstop 3051
3901 Rainbow Boulevard
Kansas City, KS 66160

P: 913-588-7667
F: 913-588-5677
isaadi@kumc.edu

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