Dr Khalid A. Fakhro graduated with Honors from the University of Chicago (USA) majoring in Biological Sciences with specialization in Cellular Biology and Molecular Genetics, and later completed his PhD in Human Genetics at Yale University (USA), where he was part of a highly selective HHMI Translational Medicine Scholars program, designed to train basic scientists to take discoveries from the bench to bedside. After two post-doctoral training fellowships abroad, he relocated to Qatar as part of the Department of Genetic Medicine at Weill Cornell Medical College in Qatar. He subsequently joined Sidra as Principal Investigator in July 2014, and became Director of the Human Genetics department, where he built a robust genomic medicine research pipeline for the hospital. In 2018, he became the inaugural Director of Precision Medicine at Sidra, heading an ambitious program where research in genomics and personalized medicine are embedded in the heart of Sidra’s academic medical enterprise. He holds adjunct faculty appointments at both Weill Cornell Medicine and at Hamad bin Khalifa University, where he teaches classes and mentors the next generation of Masters and PhD students in human genetics and genomic medicine.
Our laboratory is interested in interpreting the human genome (the instruction book of life). We approach this question from three fronts:
1. We look at the genomes of patients with rare and complex disorders at elevated frequency in Qatar, to identify genetic variants that are responsible for disease. Due to a combination of consanguinity and unique environmental exposures, the Qatari population is very well suited for gene mapping by next-generation tools, such as whole genome sequencing. Our studies make use of the vast resources at the country’s premier pediatric hospital, building long-term cohorts for continued discovery in the future.
2. We are interested in the genomic structure of Arab populations, which are severely under-represented in global databases. Using next generation sequencing and long-read technologies, we identify single mutations as well as large variants (structural changes such as deletions, duplications, inversions, translocations, etc.) in the genomes of both healthy and sick individuals. Together, these feed into novel reference genomes (and graph genomes) for Qatar.
3. We augment both of the above endeavors with other high-throughput data, such as gene expression (RNA-sequencing), metabolomics and epigenetics to link genetic variation with downstream functional consequences. We also use models such as zebrafish and cell culture to help us better understand pathophysiology in our patients, and to effectively identify personalized treatment options for intervention in the future.
Aljazi Al-Maraghi, PhDPostdoctoral FellowEmail: aalmaraghi (@) sidra.orgWaleed Aamer, PhDPostdoctoral FellowEmail: waamer (@) sidra.orgSujitha SP, PhDResearch SpecialistEmail: ssubashpad (@) sidra.orgElbay AliyevResearch SpecialistEmail: ealiyev (@) sidra.orgNjoud Al NaamaResearch SpecialistEmail: nalnaama (@) sidra.orgMuntaha MahmoudResearch CoordinatorEmail: mmahmoud4 (@) sidra.orgNajwa ElbashirResearch CoordinatorEmail: nelbashir (@) sidra.orgSura Ahmed HusseinResearch CoordinatorEmail: shussein (@) sidra.org
SELECTED PUBLICATIONS (†equal contribution, *corresponding):
- Pasquier J, Spurgeon M, Bradic M, Thomas B, Robay A, Chidiac O, Dib MJ, Turjoman R, Liberska A, Staudt M, Fakhro KA, Menzies R, Jayyousi A, Zirie M, Suwaidi JA, Malik RA, Talal T, Rafii A, Mezey J, Rodriguez-Flores J, Crystal RG, Abi Khalil C. Whole-methylome analysis of circulating monocytes in acute diabetic Charcot foot reveals differentially methylated genes involved in the formation of osteoclasts. Epigenomics (2019) 11(3):281-296.
- Da'as SI, Fakhro K, Thanassoulas A, Krishnamoorthy N, Saleh A, Calver BL, Safieh-Garabedian B, Toft E, Nounesis G, Lai FA, Nomikos M. Hypertrophic cardiomyopathy-linked variants of cardiac myosin-binding protein C3 display altered molecular properties and actin interaction. Biochem J (2018) 475(24):3933-3948.
- Fakhro KA, Elbardisi H, Arafa M, Robay A, Rodriguez-Flores JL, Al-Shakaki A, Syed N, Mezey JG, Abi Khalil C, Malek JA, Al-Ansari A, Al Said S, Crystal RG. Point-of-care whole-exome sequencing of idiopathic male infertility. Genet Med (2018) 20(11):1365-1373
- Yousri NA*, Fakhro KA*, Robay A, Rodriguez-Flores JL, Mohney RP, Zeriri H, Odeh T, Kader SA, Aldous EK, Thareja G, Kumar M, Al-Shakaki A, Chidiac OM, Mohamoud YA, Mezey JG, Malek JA, Crystal RG, Suhre K. Whole-exome sequencing identifies common and rare variant metabolic QTLs in a Middle Eastern population. Nat Commun (2018) 9(1):333
- Fadda A, Butt F, Tomei S, Deola S, Lo B, Robay A, Al-Shakaki A, Al-Hajri N, Crystal R, Kambouris M, Wang E, Marincola FM, Fakhro KA, Cugno C. Two hits in one: whole genome sequencing unveils LIG4 syndrome and urofacial syndrome in a case report of a child with complex phenotype. BMC Med Genet (2016) 17(1):84.
- Fakhro KA, Staudt MR, Ramstetter MD, Robay A, Malek JA, Badii R, Al-Marri AA, Abi Khalil C, Al-Shakaki A, Chidiac O, Stadler D, Zirie M, Jayyousi A, Salit J, Mezey JG, Crystal RG, Rodriguez-Flores JL. The Qatar genome: a population-specific tool for precision medicine in the Middle East. Hum Genome Var (2016) 3:16016.
- Rodriguez-Flores JL*, Fakhro KA*, Agosto-Perez F, Ramstetter MD, Arbiza L, Vincent TL, Robay A, Malek JA, Suhre K, Chouchane L, Badii R, Al-Nabet Al-Marri A, Abi Khalil C, Zirie M, Jayyousi A, Salit J, Keinan A, Clark AG, Crystal RG, Mezey JG. Indigenous Arabs are descendants of the earliest split from ancient Eurasian populations. Genome Res (2011) 26(2):151-62.
- Fakhro KA, Yousri NA, Rodriguez-Flores JL, Robay A, Staudt MR, Agosto-Perez F, Salit J, Malek JA, Suhre K, Jayyousi A, Zirie M, Stadler D, Mezey JG, Crystal RG. Copy number variations in the genome of the Qatari population. BMC Genomics (2015) 16:834.
- Rodriguez-Flores JL*, Fakhro K*, Hackett NR, Salit J, Fuller J, Agosto-Perez F, Gharbiah M, Malek JA, Zirie M, Jayyousi A, Badii R, Al-Nabet Al-Marri A, Chouchane L, Stadler DJ, Mezey JG, Crystal RG. Exome sequencing identifies potential risk variants for Mendelian disorders at high prevalence in Qatar. Hum Mutat (2014)35(1):105-16.
- Fakhro KA, Choi M, Ware SM, Belmont JW, Towbin JA, Lifton RP, Khokha MK, Brueckner M. Rare copy number variations in congenital heart disease patients identify unique genes in left-right patterning. Proc Natl Acad Sci U S A (2011)108(7):2915-20.