Pawel Stankiewicz, M.D., Ph.D.
Associate Professor of Molecular and Human Genetics
Assistant Director, Cytogenetics Laboratory, BCM Medical Genetics Laboratories
M.D., Medical University of Warsaw, Poland, 1991
Ph.D., Institute of Mother and Child, Warsaw, Poland, 1999
Postdoc, Baylor College of Medicine, 2000-2003
Dr. Habil. (D. Sc.), Institute of Mother and Child, Warsaw, Poland, 2006
American Board of Medical Genetics: Clinical Cytogenetics
Member, American Society of Human Genetics
Member, European Society of Human Genetics
Member, Polish Society of Human Genetics
Genomic Disorders: The main focus of our research is better understanding the molecular mechanisms and phenotypic effects of genomic rearrangements. We are particularly interested in elucidating the role of higher-order genomic architectural features such as low-copy repeats (LCRs) in genomic instability. LCRs have been shown to mediate non-allelic homologous recombination and stimulate other DNA replication errors in formation of genomic rearrangements. Using several different molecular cytogenetic techniques, including oligonucleotide array comparative genomic hybridization (array CGH), we are identifying and characterizing the breakpoints of submicroscopic chromosome deletions and duplications to infer mechanism and study patients to determine potential phenotypic consequences of copy-number variation (CNV).
We have demonstrated that haploinsufficiency of the transcriptional factor FOXF1 gene on 16q24.1 results in a lethal neonatal diffuse developmental disorder alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV). Infants affected with ACD/MPV develop severe respiratory distress with pulmonary hypertension within the first two days of life and despite of intensive care die usually within first few days of life. Up to 80 percent of infants with ACD/MPV have additional malformations affecting the cardiac, gastrointestinal, and genitourinary systems that resemble VACTERL association. In contrast to the association of point mutations in FOXF1 with bowel malrotation, microdeletions of FOXF1 were associated with hypoplastic left heart syndrome and gastrointestinal atresias, likely due to haploinsufficiency for the neighboring FOXC2. These differences reveal the phenotypic consequences of gene alterations in cis. We are also investigating the role of IncRNAs in a long range cis-regulation of FOXF1 expression.
Clinical diagnostics: We continue to constantly improve novel versions of Chromosome Microarray Analysis (CMA) in the MGL Microarray and Cytogenetics Laboratories to increase the detection rate and enable better genotype-phenotype correlations.
- Dittwald P, Gambin T, Szafranski P, Li J, Amato S, Divon MY, Rodríguez Rojas LX, Elton LE, Scott DA, Schaaf CP, Torres-Martinez W, Stevens AK, Rosenfeld JA, Agadi S, Francis D, Kang SH, Breman A, Lalani SR, Bacino CA, Bi W, Milosavljevic A, Beaudet AL, Patel A, Shaw CA, Lupski JR, Gambin A, Cheung SW, Stankiewicz P (2013). NAHR-mediated copy-number variants in a clinical population: Mechanistic insights into both genomic disorders and Mendelizing traits. Genome Res. 23(9): 1395-409. PubMed PMID: 23657883
- Sen P, Yang Y, Navarro C, Silva I, Szafranski P, Kolodziejska KE, Dharmadhikari AV, Mostafa H, Kozakewich H, Kearney D, Cahill JB, Whitt M, Bilic M, Margraf L, Charles A, Goldblatt J, Gibson K, Lantz PE, Garvin AJ, Petty J, Kiblawi Z, Zuppan C, McConkie-Rosell A, McDonald MT, Peterson-Carmichael SL, Gaede JT, Shivanna B, Schady D, Friedlich PS, Hays SR, Palafoll IV, Siebers-Renelt U, Bohring A, Finn LS, Siebert JR, Galambos C, Nguyen L, Riley M, Chassaing N, Vigouroux A, Rocha G, Fernandes S, Brumbaugh J, Roberts K, Ho-Ming L, Lo IF, Lam S, Gerychova R, Jezova M, Valaskova I, Fellmann F, Afshar K, Giannoni E, Muhlethaler V, Liang J, Beckmann JS, Lioy J, Deshmukh H, Srinivasan L, Swarr DT, Sloman M, Shaw-Smith C, van Loon RL, Hagman C, Sznajer Y, Barrea C, Galant C, Detaille T, Wambach JA, Cole FS, Hamvas A, Prince LS, Diderich KE, Brooks AS, Verdijk RM, Ravindranathan H, Sugo E, Mowat D, Baker ML, Langston C, Welty S, Stankiewicz P (2013). Novel FOXF1 mutations in sporadic and familial cases of alveolar capillary dysplasia with misaligned pulmonary veins imply a role for its DNA binding domain. Hum. Mutat. 34(6): 801-11. PubMed PMID: 23505205
- Szafranski P, Dharmadhikari AV, Brosens E, Gurha P, Kolodziejska KE, Zhishuo O, Dittwald P, Majewski T, Mohan KN, Chen B, Person R, Tibboel D, de Klein A, Pinner J, Chopra M, Malcolm G, Peters G, Arbuckle S, Guiang SF III, Hustead VA, Jessurun J, Hirsch R, Witte DP, Maystadt I, Sebire N, Fisher R, Langston C, Sen P, Stankiewicz P (2013). Small non-coding differentially-methylated copy-number variants, including lncRNA genes, cause a lethal lung developmental disorder. Genome Res. 23(1): 23-33. PubMed PMID: 23034409
- Dharmadhikari AV, Kang SH, Szafranski P, Person RE, Sampath S, Prakash SK, Bader PI, Phillips JA 3rd, Hannig V, Williams M, Vinson SS, Wilfong AA, Reimschisel TE, Craigen WJ, Patel A, Bi W, Lupski JR, Belmont J, Cheung SW, Stankiewicz P (2012). Small rare recurrent deletions and reciprocal duplications in 2q21.1, including brain-specific ARHGEF4 and GPR148. Hum. Mol. Genet. 21(15): 3345-55. PubMed PMID: 22543972
- Stankiewicz P, Kulkarni S, Dharmadhikari AV, Sampath S, Bhatt SS, Shaikh TH, Xia Z, Pursley AN, Cooper ML, Shinawi M, Paciorkowski AR, Grange DK, Noetzel MJ, Saunders S, Simons P, Summar M, Lee B, Scaglia F, Fellmann F, Martinet D, Beckmann JS, Asamoah A, Platky K, Sparks S, Martin AS, Madan-Khetarpal S, Hoover J, Medne L, Bonnemann CG, Moeschler JB, Vallee SE, Parikh S, Irwin P, Dalzell VP, Smith WE, Banks VC, Flannery DB, Lovell CM, Bellus GA, Golden-Grant K, Gorski JL, Kussmann JL, McGregor TL, Hamid R, Pfotenhauer J, Ballif BC, Shaw CA, Kang SH, Bacino CA, Patel A, Rosenfeld JA, Cheung SW, Shaffer LG (2012). Recurrent deletions and reciprocal duplications of 10q11.21q11.23 including CHAT and SLC18A3 are likely mediated by complex low-copy repeats. Hum. Mutat. 33(1): 165-79. PubMed PMID: 21948486
- Ramocki MB, Bartnik M, Szafranski P, Kołodziejska KE, Xia Z, Bravo J, Miller GS, Rodriguez DL, Williams CA, Bader PI, Szczepanik E, Mazurczak T, Antczak-Marach D, Coldwell JG, Akman CI, McAlmon K, Cohen MP, McGrath J, Roeder E, Mueller J, Kang SH, Bacino CA, Patel A, Bocian E, Shaw CA, Cheung SW, Mazurczak T, Stankiewicz P (2010). Recurrent distal 7q11.23 deletion including HIP1 and YWHAG identified in patients with intellectual disabilities, epilepsy, and neurobehavioral problems. Am. J. Hum. Genet. 87(6): 857-65. PubMed PMID: 21109226
- Boone PM, Bacino CA, Shaw CA, Eng PA, Hixson PM, Pursley AN, Kang SH, Yang Y, Wiszniewska J, Nowakowska BA, Del Gaudio D, Xia Z, Simpson-Patel G, Immken LL, Gibson JB, Tsai AC, Bowers JA, Reimschisel TE, Schaaf CP, Potocki L, Scaglia F, Gambin T, Sykulski M, Bartnik M, Derwinska K, Wisniowiecka-Kowalnik B, Lalani SR, Probst FJ, Bi W, Beaudet AL, Patel A, Lupski JR, Cheung SW, Stankiewicz P (2010). Detection of clinically relevant exonic copy-number changes by array CGH. Hum. Mutat. 31(12): 1326-42. PubMed PMID: 20848651
- Szafranski P, Schaaf CP, Person RE, Gibson IB, Xia Z, Mahadevan S, Wiszniewska J, Bacino CA, Lalani S, Potocki L, Kang SH, Patel A, Cheung SW, Probst FJ, Graham BH, Shinawi M, Beaudet AL, Stankiewicz P (2010). Structures and molecular mechanisms for common 15q13.3 microduplications involving CHRNA7: benign or pathological? Hum. Mutat. 31(7): 840-50. PubMed PMID: 20506139
- Shinawi M, Schaaf CP, Bhatt SS, Xia Z, Patel A, Cheung SW, Lanpher B, Nagl S, Herding HS, Nevinny-Stickel C, Immken LL, Patel GS, German JR, Beaudet AL, Stankiewicz P (2009). A small recurrent deletion within 15q13.3 is associated with a range of neurodevelopmental phenotypes. Nat. Genet. 41(12): 1269-71. PubMed PMID: 19898479
- Stankiewicz P, Sen P, Bhatt SS, Storer M, Xia Z, Bejjani BA, Ou Z, Wiszniewska J, Driscoll DJ, Maisenbacher MK, Bolivar J, Bauer M, Zackai EH, McDonald-McGinn D, Nowaczyk MM, Murray M, Hustead V, Mascotti K, Schultz R, Hallam L, McRae D, Nicholson AG, Newbury R, Durham-O'Donnell J, Knight G, Kini U, Shaikh TH, Martin V, Tyreman M, Simonic I, Willatt L, Paterson J, Mehta S, Rajan D, Fitzgerald T, Gribble S, Prigmore E, Patel A, Shaffer LG, Carter NP, Cheung SW, Langston C, Shaw-Smith C (2009). Genomic and genic deletions of the FOX gene cluster on 16q24.1 and inactivating mutations of FOXF1 cause alveolar capillary dysplasia and other malformations. Am. J. Hum. Genet. 84(6): 780-91. PubMed PMID: 19500772
Pawel Stankiewicz, M.D., Ph.D.
Department of Molecular and Human Genetics
Baylor College of Medicine
One Baylor Plaza, BCM 225
Houston, TX, 77030, U.S.A.