Department of Pediatrics

Clinical Interests

Dr. Beth Kozel is a clinical geneticist and a Lasker Clinical Research Scholar. She directs the Laboratory of Vascular and Matrix Genetics at the National Heart, Lung and Blood Institute at the National Institutes of Health. She is also the director of the Williams syndrome clinic at Washington University School of Medicine/St. Louis Children’s Hospital. At the NIH, her emphasis is on understanding the genetic underpinnings of rare vascular diseases, especially those caused by connective tissue defects.
With extensive experience in vascular and matrix biology as well as genetics, Dr. Kozel focuses her work on the study of elastin-mediated arteriopathy in mice and humans. Work by her group has contributed to greater understanding of the process of elastic fiber assembly as well as the mechanism by which elastin insufficiency causes arterial stiffness. Current efforts include identification of genes/pathways that modify the impact of elastin insufficiency on blood vessels and harnessing those pathways to design rational treatments for individuals with those diseases.

Education

• BA, Summa Cum Laude, Washington University in St. Louis, 1996
• MD, Washington University School of Medicine, 2004
• PhD, Washington University School of Medicine, 2004

Training

• Resident, St. Louis Children's Hospital, 2004 - 2007
• Resident (Fellow), Washington University School of Medicine, 2007 - 2009

Licensure and Board Certification

• 2007 - PresAmerican Board of Pediatrics
• 2007 - PresMO, Unrestricted Medical License
• 2009 - PresAmerican Board of Medical Genetics

Honors and Awards

• Teresa Vietti Fellowship Award, 2010
• Co-Chair for the 2011 Gordon-Kenan Research Seminar, Elastin and Elastic Fibers, 2010 - 2011
• NIH K12 Scholar 1K12 (HL089968), 2010 - 2011
• Scholar of the Child Health Research Center of Excellence in Developmental Biology at Washington University School of Medicine, 2011 - 2013
• NIH K08 Recipient 1K08 (HL109076), 2011 - 2016
• Children's Discovery Institute Faculty Scholar, 2011 - 2016
• Lasker Clinical Research Scholar, 2015 - Pres
• Williams Syndrome Association Heart to Heart Award, 2015

Recent Publications view all (32)

Publication Co-Authors

Carmen Halabi, M.D., Ph.D.

Dustin Baldridge

Marwan Shinawi, M.D.

Linda Manwaring

Charles Canter, M.D.

Dennis J. Dietzen, Ph.D.

Dorothy Katherine Grange, M.D.

Jennifer Heeley

Tomi L. Toler, MS, CGC

Robert J. Hayashi, M.D.

Vikas Dharnidharka, M.D., M.P.H.

Washington University has a long tradition of collaboration amongst colleagues.The faculty above have co-authored publications with Beth A. Kozel, M.D., Ph.D.

1. Duque Lasio ML, Kozel BA. Elastin-driven genetic diseases. Matrix Biol. 2018;71-72:144-160. PMID:29501665 
2. Kopp ND, Parrish PCR, Lugo M, Dougherty JD, Kozel BA. Exome sequencing of 85 Williams-Beuren syndrome cases rules out coding variation as a major contributor to remaining variance in social behavior. Mol Genet Genomic Med. 2018;6(5):749-765. PMCID:PMC6160704  PMID:30008175 
3. Groves AP, Gettinger K, Druley TE, Kozel BA, Shinawi M, Mohrmann C, Henry J, Jacobi C, Trinkaus K, Hayashi RJ. Special Therapy and Psychosocial Needs Identified in a Multidisciplinary Cancer Predisposition Syndrome Clinic. J Pediatr Hematol Oncol. 2018. PMID:30028825 
4. Knutsen RH, Beeman SC, Broekelmann TJ, Liu D, Tsang KM, Kovacs A, Ye L, Danback JR, Watson A, Wardlaw A, Wagenseil JE, Garbow JR, Shoykhet M, Kozel BA. Minoxidil improves vascular compliance, restores cerebral blood flow, and alters extracellular matrix gene expression in a model of chronic vascular stiffness. Am J Physiol Heart Circ Physiol. 2018;315(1):H18-H32. PMCID:PMC6087770  PMID:29498532 
5. O'Bryhim BE, Kozel BA, Lueder GT. Novel retinal findings in peroxisomal biogenesis disorders. Ophthalmic Genet. 2018;39(3):377-379. PMID:29377746 
6. Kruszka P, Porras AR, de Souza DH, Moresco A, Huckstadt V, Gill AD, Boyle AP, Hu T, Addissie YA, Mok GTK, Tekendo-Ngongang C, Fieggen K, Prijoles EJ, Tanpaiboon P, Honey E, Luk HM, Lo IFM, Thong MK, Muthukumarasamy P, Jones KL, Belhassan K, Ouldim K, El Bouchikhi I, Bouguenouch L, Shukla A, Girisha KM, Sirisena ND, Dissanayake VHW, Paththinige CS, Mishra R, Kisling MS, Ferreira CR, de Herreros MB, Lee NC, Jamuar SS, Lai A, Tan ES, Ying Lim J, Wen-Min CB, Gupta N, Lotz-Esquivel S, Badilla-Porras R, Hussen DF, El Ruby MO, Ashaat EA, Patil SJ, Dowsett L, Eaton A, Innes AM, Shotelersuk V, Badoe Ë, Wonkam A, Obregon MG, Chung BHY, Trubnykova M, La Serna J, Gallardo Jugo BE, Chávez Pastor M, Abarca Barriga HH, Megarbane A, Kozel BA, van Haelst MM, Stevenson RE, Summar M, Adeyemo AA, Morris CA, Moretti-Ferreira D, Linguraru MG, Muenke M. Williams-Beuren syndrome in diverse populations. Am J Med Genet A. 2018;176(5):1128-1136. PMCID:PMC6007881  PMID:29681090 
7. Baldridge D, Heeley J, Vineyard M, Manwaring L, Toler TL, Fassi E, Fiala E, Brown S, Goss CW, Willing M, Grange DK, Kozel BA, Shinawi M. The Exome Clinic and the role of medical genetics expertise in the interpretation of exome sequencing results. Genet Med. 2017;19(9):1040-1048. PMCID:PMC5581723  PMID:28252636 
8. Kulsum-Mecci N, Goss C, Kozel BA, Garbutt JM, Schechtman KB, Dharnidharka VR. Effects of Obesity and Hypertension on Pulse Wave Velocity in Children. J Clin Hypertens (Greenwich). 2017;19(3):221-226. PMID:27511880 
9. Sindhar S, Lugo M, Levin MD, Danback JR, Brink BD, Yu E, Dietzen DJ, Clark AL, Purgert CA, Waxler JL, Elder RW, Pober BR, Kozel BA. Hypercalcemia in Patients with Williams-Beuren Syndrome. J Pediatr. 2016;178:254-260.e4. PMCID:PMC5085847  PMID:27574996 
10. Levin MD, Singh GK, Zhang HX, Uchida K, Kozel BA, Stein PK, Kovacs A, Westenbroek RE, Catterall WA, Grange DK, Nichols CG. KATP channel gain-of-function leads to increased myocardial L-type Ca2+ current and contractility in Cantu syndrome. Proc Natl Acad Sci U S A. 2016;113(24):6773-8. PMCID:PMC4914204  PMID:27247394 
11. Halabi CM, Broekelmann TJ, Knutsen RH, Ye L, Mecham RP, Kozel BA. Chronic antihypertensive treatment improves pulse pressure but not large artery mechanics in a mouse model of congenital vascular stiffness. Am J Physiol Heart Circ Physiol. 2015;309(5):H1008-16. PMCID:PMC4591401  PMID:26232234 
12. Kozel BA, Su CT, Danback JR, Minster RL, Madan-Khetarpal S, McConnell JS, Mac Neal MK, Levine KL, Wilson RC, Sciurba FC, Urban Z. Biomechanical properties of the skin in cutis laxa. J Invest Dermatol. 2014;134(11):2836-8. doi:10.1038/jid.2014.224  PMCID:PMC4199921  PMID:24844858 
13. DeMarsilis AJ, Walji TA, Maedeker JA, Stoka KV, Kozel BA, Mecham RP, Wagenseil JE, Craft CS. Elastin Insufficiency Predisposes Mice to Impaired Glucose Metabolism. J Mol Genet Med. 2014;8(3). doi:10.4172/1747-0862.1000129  PMCID:PMC4497575  PMID:26167199 
14. Kozel BA, Bayliss SJ, Berk DR, Waxler JL, Knutsen RH, Danback JR, Pober BR. Skin findings in Williams syndrome. Am J Med Genet A. 2014;164A(9):2217-25. doi:10.1002/ajmg.a.36628  PMCID:PMC4134746  PMID:24920525 
15. Koehler U, Pabst B, Pober B, Kozel B. Clinical utility gene card for: Williams-Beuren Syndrome [7q11.23]. Eur J Hum Genet. 2014;22(9). doi:10.1038/ejhg.2014.28  PMCID:PMC4135419  PMID:24569604 
16. Cheng YW, Tan CA, Minor A, Arndt K, Wysinger L, Grange DK, Kozel BA, Robin NH, Waggoner D, Fitzpatrick C, Das S, Del Gaudio D. Copy number analysis of NIPBL in a cohort of 510 patients reveals rare copy number variants and a mosaic deletion. Mol Genet Genomic Med. 2014;2(2):115-23. doi:10.1002/mgg3.48  PMCID:PMC3960053  PMID:24689074 
17. Osei-Owusu P, Knutsen RH, Kozel BA, Dietrich HH, Blumer KJ, Mecham RP. Altered reactivity of resistance vasculature contributes to hypertension in elastin insufficiency. Am J Physiol Heart Circ Physiol. 2014;306(5):H654-66. PMCID:PMC3949062  PMID:24414067 
18. Kozel BA, Danback JR, Waxler JL, Knutsen RH, de Las Fuentes L, Reusz GS, Kis E, Bhatt AB, Pober BR. Williams syndrome predisposes to vascular stiffness modified by antihypertensive use and copy number changes in NCF1. Hypertension. 2014;63(1):74-9. PMCID:PMC3932371  PMID:24126171 
19. Schilter KF, Reis LM, Schneider A, Bardakjian TM, Abdul-Rahman O, Kozel BA, Zimmerman HH, Broeckel U, Semina EV. Whole-genome copy number variation analysis in anophthalmia and microphthalmia. Clin Genet. 2013;84(5):473-81. doi:10.1111/cge.12202  PMCID:PMC3985344  PMID:23701296 
20. Sugitani H, Hirano E, Knutsen RH, Shifren A, Wagenseil JE, Ciliberto C, Kozel BA, Urban Z, Davis EC, Broekelmann TJ, Mecham RP. Alternative splicing and tissue-specific elastin misassembly act as biological modifiers of human elastin gene frameshift mutations associated with dominant cutis laxa. J Biol Chem. 2012;287(26):22055-67. doi:10.1074/jbc.M111.327940  PMCID:PMC3381164  PMID:22573328 
21. Nagamani SC, Erez A, Bay C, Pettigrew A, Lalani SR, Herman K, Graham BH, Nowaczyk MJ, Proud M, Craigen WJ, Hopkins B, Kozel B, Plunkett K, Hixson P, Stankiewicz P, Patel A, Cheung SW. Delineation of a deletion region critical for corpus callosal abnormalities in chromosome 1q43-q44. Eur J Hum Genet. 2012;20(2):176-9. doi:10.1038/ejhg.2011.171  PMCID:PMC3260920  PMID:21934713 
22. Kozel BA, Knutsen RH, Ye L, Ciliberto CH, Broekelmann TJ, Mecham RP. Genetic modifiers of cardiovascular phenotype caused by elastin haploinsufficiency act by extrinsic noncomplementation. J Biol Chem. 2011;286(52):44926-36. doi:10.1074/jbc.M111.274779  PMCID:PMC3248007  PMID:22049077 
23. Reis LM, Tyler RC, Schilter KF, Abdul-Rahman O, Innis JW, Kozel BA, Schneider AS, Bardakjian TM, Lose EJ, Martin DM, Broeckel U, Semina EV. BMP4 loss-of-function mutations in developmental eye disorders including SHORT syndrome. Hum Genet. 2011;130(4):495-504. doi:10.1007/s00439-011-0968-y  PMCID:PMC3178759  PMID:21340693 
24. Shinawi M, Liu P, Kang SH, Shen J, Belmont JW, Scott DA, Probst FJ, Craigen WJ, Graham BH, Pursley A, Clark G, Lee J, Proud M, Stocco A, Rodriguez DL, Kozel BA, Sparagana S, Roeder ER, McGrew SG, Kurczynski TW, Allison LJ, Amato S, Savage S, Patel A, Stankiewicz P, Beaudet AL, Cheung SW, Lupski JR. Recurrent reciprocal 16p11.2 rearrangements associated with global developmental delay, behavioural problems, dysmorphism, epilepsy, and abnormal head size. J Med Genet. 2010;47(5):332-41. doi:10.1136/jmg.2009.073015  PMCID:PMC3158566  PMID:19914906 
25. Toib A, Grange DK, Kozel BA, Ewald GA, White FV, Canter CE. Distinct clinical and histopathological presentations of Danon cardiomyopathy in young women. J Am Coll Cardiol. 2010;55(4):408-10. PMID:20117447 
26. Ware SM, El-Hassan N, Kahler SG, Zhang Q, Ma YW, Miller E, Wong B, Spicer RL, Craigen WJ, Kozel BA, Grange DK, Wong LJ. Infantile cardiomyopathy caused by a mutation in the overlapping region of mitochondrial ATPase 6 and 8 genes. J Med Genet. 2009;46(5):308-14. PMID:19188198 
27. Kozel BA, Rongish BJ, Czirok A, Zach J, Little CD, Davis EC, Knutsen RH, Wagenseil JE, Levy MA, Mecham RP. Elastic fiber formation: a dynamic view of extracellular matrix assembly using timer reporters. J Cell Physiol. 2006;207(1):87-96. doi:10.1002/jcp.20546  PMID:16261592 
28. Czirok A, Zach J, Kozel BA, Mecham RP, Davis EC, Rongish BJ. Elastic fiber macro-assembly is a hierarchical, cell motion-mediated process. J Cell Physiol. 2006;207(1):97-106. doi:10.1002/jcp.20573  PMID:16331676 
29. Broekelmann TJ, Kozel BA, Ishibashi H, Werneck CC, Keeley FW, Zhang L, Mecham RP. Tropoelastin interacts with cell-surface glycosaminoglycans via its COOH-terminal domain. J Biol Chem. 2005;280(49):40939-47. doi:10.1074/jbc.M507309200  PMID:16192266 
30. Kozel BA, Ciliberto CH, Mecham RP. Deposition of tropoelastin into the extracellular matrix requires a competent elastic fiber scaffold but not live cells. Matrix Biol. 2004;23(1):23-34. doi:10.1016/j.matbio.2004.02.004  PMID:15172035 
31. Kozel BA, Wachi H, Davis EC, Mecham RP. Domains in tropoelastin that mediate elastin deposition in vitro and in vivo. J Biol Chem. 2003;278(20):18491-8. doi:10.1074/jbc.M212715200  PMID:12626514 
32. Lanyi A, Li B, Li S, Talmadge CB, Brichacek B, Davis JR, Kozel BA, Trask B, van den Engh G, Uzvolgyi E, Stanbridge EJ, Nelson DL, Chinault C, Heslop H, Gross TG, Seemayer TA, Klein G, Purtilo DT, Sumegi J. A yeast artificial chromosome (YAC) contig encompassing the critical region of the X-linked lymphoproliferative disease (XLP) locus. Genomics. 1997;39(1):55-65. doi:10.1006/geno.1996.4466  PMID:9027486