Irfan Saadi, MS, PhD

Professional Background

Dr. Irfan Saadi received his B.Sc. (Hon.) and M.Sc. degrees in Biology from McGill University in Montreal, Canada, where he began his research career in Dr. Rima Rozen’s laboratory working on genotype-phenotype correlation in patients with cystinuria. He earned his Ph.D. in Genetics from the University of Iowa in Dr. Andrew Russo’s laboratory studying the molecular consequences of disease-causing mutations in Axenfeld-Rieger syndrome. His postdoctoral training at Harvard was in genetic analyses of palate and tooth development with Dr. Richard Maas, a preeminent scholar of craniofacial morphogenesis. Dr. Saadi joined the University of Kansas Medical Center in 2011 as an Assistant Professor. He is currently an Associate Professor with Tenure in the Department of Cell Biology and Physiology. His research is focused on understanding the molecular mechanisms underlying embryonic morphogenesis and congenital anomalies.

• BS, Biology, McGill University, Montreal, Quebec
• MS, Biology, McGill University, Montreal, Quebec
• PhD, Genetics, University of Iowa
• Post Doctoral Fellowship, Developmental Genetics, Brigham and Women’s Hospital/Harvard Medical School
• Post Doctoral Fellowship, Tooth Development, The Forsyth Institute

• American Association for Anatomy, Strategic Plan Review, Member, 2024 - 2024
• Society for Craniofacial Genetics and Developmental Biology, Board, Member, 2023 - 2026
• American Association for Anatomy, Scientific Affairs Committee, Member, 2020 - 2022
• American Association for Anatomy, Member, 2017 - Present
• Society for Craniofacial Genetics and Developmental Biology, Member, 2013 - Present
• American Society of Human Genetics, Member, 1999 - Present

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Research

Overview

Craniofacial malformations afflict about 5% of all infants born in the United States and comprise approximately one-third of all birth defects. While a number of contributory genes have been identified, they account for only a subset of cases at best. Thus, there is continued need to identify additional genes and to understand underlying pathogenetic mechanisms. We are currently investigating the role of a novel cytoskeletal protein, SPECC1L, in craniofacial morphogenesis and malformation.

To explore the role of SPECC1L, we are using four broad approaches: 1) Human Genetics – we continue to collaborate with clinicians nationally to identify SPECC1L mutations in patients with syndromic and isolated orofacial clefting [Saadi, 2011; Kruszka, 2015]. 2) Mouse Models – we have now generated an allelic series of Specc1l mutants, including knockout, hypomorphic, and point mutants. These alleles allow us to vary Specc1l dosage, which results in an array of phenotypes, including embryonic lethality, cleft palate, exencephaly, hydrocephalus and behavioral deficits. 3) Cell Biology – we have shown that SPECC1L regulates the density of cell-cell contacts in pre-migratory neural crest cells resulting in defective delamination in severe mutants [Wilson, 2016]. We are using live-cell imaging to show that SPECC1L also regulates cell-cell communication required for collective migration of neural crest cells in hypomorphic and point mutants. 4) Molecular Biology – we have shown that SPECC1L is a novel regulator of PI3K-AKT signaling. We are now using RNA-seq and protein-protein interactions to show how SPECC1L regulates the stability of AKT and other signaling molecules.

Understanding the role of SPECC1L will provide i) valuable insights into modulation of cell-cell contacts and cell adhesion during craniofacial morphogenesis, ii) a novel network of genes that may be involved in craniofacial malformation, and iii) potential therapeutic targets for orofacial clefting.

• Alkuraya Fowzan S, Saadi Irfan, Lund Jennifer J, Turbe-Doan Annick, Morton Cynthia C, Maas Richard L. 2006. SUMO1 Haploinsufficiency Leads to Cleft Lip and Palate. Science, 313 (5794), 1751-1751. https://doi.org/10.1126/science.1128406
• Lachke Salil A, Alkuraya Fowzan S, Kneeland Stephen C, Ohn Takbum, Aboukhalil Anton, Howell Gareth R, Saadi Irfan, Cavallesco Resy, Yue Yingzi, Tsai Anne C-H, Nair K. Saidas, Cosma Mihai I, Smith Richard S, Hodges Emily, AlFadhli Suad M, Al-Hajeri Amal, Shamseldin Hanan E, Behbehani AbdulMutalib, Hannon Gregory J, Bulyk Martha L, Drack Arlene V, Anderson Paul J, John Simon W, Maas Richard L. 2011. Mutations in the RNA Granule Component TDRD7 Cause Cataract and Glaucoma. Science, 331 (6024), 1571-1576. https://doi.org/10.1126/science.1195970
• Saadi Irfan, Alkuraya Fowzan S, Gisselbrecht Stephen S, Goessling Wolfram, Cavallesco Resy, Turbe-Doan Annick, Petrin Aline L, Harris James, Siddiqui Ursela, Grix Arthur W, Hove Hanne D, Leboulch Philippe, Glover Thomas W, Morton Cynthia C, Richieri-Costa Antonio, Murray Jeffrey C, Erickson Robert P, Maas Richard L. 2011. Deficiency of the Cytoskeletal Protein SPECC1L Leads to Oblique Facial Clefting. The American Journal of Human Genetics, 89 (1), 44-55. https://doi.org/10.1016/j.ajhg.2011.05.023
• Saadi Irfan, Das Pragnya, Zhao Minglian, Raj Lakshmi, Ruspita Intan, Xia Yan, Papaioannou Virginia E, Bei Marianna. 2013. Msx1andTbx2antagonistically regulateBmp4expression during the bud-to-cap stage transition in tooth development. Development, 140 (13), 2697-2702. https://doi.org/10.1242/dev.088393
• Dasouki Majed J, Rafi Syed K, Olm-Shipman Adam J, Wilson Nathan R, Abhyankar Sunil, Ganter Brigitte, Furness L. Mike, Fang Jianwen, Calado Rodrigo T, Saadi Irfan. 2013. Exome sequencing reveals a thrombopoietin ligand mutation in a Micronesian family with autosomal recessive aplastic anemia. Blood, 122 (20), 3440-3449. https://doi.org/10.1182/blood-2012-12-473538
• Wilson Nathan R, Olm-Shipman Adam J, Acevedo Diana S, Palaniyandi Kanagaraj, Hall Everett G, Kosa Edina, Stumpff Kelly M, Smith Guerin J, Pitstick Lenore, Liao Eric C, Bjork Bryan C, Czirok Andras, Saadi Irfan. 2016. SPECC1L deficiency results in increased adherens junction stability and reduced cranial neural crest cell delamination. Scientific Reports, 6 (1), 17735. https://doi.org/10.1038/srep17735
• Hall Everett G, Wenger Luke W, Wilson Nathan R, Undurty-Akella Sraavya S, Standley Jennifer, Augustine-Akpan Eno-Abasi, Kousa Youssef A, Acevedo Diana S, Goering Jeremy P, Pitstick Lenore, Natsume Nagato, Paroya Shahnawaz M, Busch Tamara D, Ito Masaaki, Mori Akihiro, Imura Hideto, Schultz-Rogers Laura E, Klee Eric W, Babovic-Vuksanovic Dusica, Kroc Sarah A, Adeyemo Wasiu L, Eshete Mekonen A, Bjork Bryan C, Suzuki Satoshi, Murray Jeffrey C, Schutte Brian C, Butali Azeez, Saadi Irfan. 2020. SPECC1L regulates palate development downstream of IRF6. Human Molecular Genetics, 29 (5), 845-858. https://doi.org/10.1093/hmg/ddaa002
• Goering Jeremy P, Wenger Luke W, Stetsiv Marta, Moedritzer Michael, Hall Everett G, Isai Dona Greta, Jack Brittany M, Umar Zaid, Rickabaugh Madison K, Czirok Andras, Saadi Irfan. 2021. In-frame deletion of SPECC1L microtubule association domain results in gain-of-function phenotypes affecting embryonic tissue movement and fusion events. Human Molecular Genetics, 31 (1), 18-31. https://doi.org/10.1093/hmg/ddab211