Nancy B. Spinner, PhD, FACMG

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Nancy B. Spinner, PhD, FACMG is the Chief of the Division of Genomic Diagnostics at Children's Hospital of Philadelphia.

Areas of Expertise: Alagille syndrome and other chromosome 20 abnormalities, Cytogenetic studies of patients with developmental and syndromic disorders permitting identification of genomic rearrangements associated with genetic disease, Molecular cytogenetics
Locations: Main Hospital
Appointments and Referrals: 1-800-TRY-CHOP (1-800-879-2467)

Background

The Spinner Laboratory studies the genetics of several pediatric disorders focusing on both identifying the specific genes that cause disease, and understanding how mutations in these genes can cause related clinical phenotypes. 

Current projects focus on utilization of exome and whole genome sequencing for pediatric diagnosis, understanding the genetics of two pediatric liver disorders, Alagille syndrome and biliary atresia, and molecular analysis of ring chromosome 14 and 20, both of which are associated with seizures. 

Their clinical sequencing project is carried out in collaboration with Dr. Ian Krantz’s laboratory and is part of the Clinical Sequencing Exploratory Research (CSER) project, funded by the NHGRI. The goals of this network are to identify best practices for pediatric exome sequencing.

Our work on Alagille syndrome and Biliary Atresia is carried out in collaboration with Drs. Marcella Devoto, Kathy Loomes, Ian Krantz and David Piccoli at CHOP, and as part of the NIDDK funded Childhood Liver Disease Research Network (ChiLDReN). Our work on biliary atresia is aimed at identifying genetic susceptibility factors and we are using GWAS, exome sequencing and analysis of copy number variation to look for genetic underpinnings for this clearly complex and likely heterogeneous disorder. 

A more recent project is to understand the mechanism by which ring chromosomes cause human disease and in particular we are focusing on two ring chromosomes that are associated with seizures.  Even in cases where the ring chromosomes are molecularly intact, with no deletions or duplications, affected individuals have a clinical phenotype, and we are working with Drs. Stewart Anderson, Jay Mills and Laura Conlin, to develop a neuronal cell model for these ring chromosomes.  Since the seizure phenotype emerges with age of the patients, we believe that understanding the cause of the seizures may lead us to better treatments.

Education and Training

Fellowship

Genetics - The Children's Hospital of Philadelphia, Philadelphia, PA

Additional Training

Postdoctoral training in cytogenetics - The Children' Hospital of Philadelphia and the University of Pennsylvania School of Medicine

Board Certification

American Board of Medical Genetics
American Board of Medical Genetics/Cytogenetics

Graduate Degree

PhD in Genetics - University of California, Berkeley/San Diego State, La Jolla, CA

Titles and Academic Titles

Chief, Division of Genomic Diagnostics

Evelyn Willing Bromley Endowed Chair in Pathology and Clinical Laboratories

Professor of Pathology and Genetics, Perelman School of Medicine at the University of Pennsylvania

Departments and Services

Research Interests

Identification and analysis of genes involved in pediatric disease, with focus on Ring Chromosome 20 syndrome
Alagille syndrome and biliary atresia

Publications

Papers

2016

Tsai, E.A., Gilbert, M.A., Grochowski, C.M., Underkoffler, L.A., Meng, H., Zhang, X., Wang, M.M., Shitaye, H., Hankenson, K.D., Piccoli, D., Lin, H., Kamath, B.M., Devoto, M., Spinner, N.B., Loomes, K.M.: THBS2 is a candidate modifier of liver disease severity in Alagille syndrome". Cellular and Molecular Gastroenterology and Hepatology. In the Press (July 2016) July 2016.

Green, R. C.,  Goddard, K. A.,  Jarvik, G. P.,  Amendola, L. M.,  Appelbaum, P. S.,  Berg, J. S.,  Bernhardt, B. A.,  Biesecker, L. G.,  Biswas, S.,  Blout, C. L.,  Bowling, K. M.,  Brothers, K. B.,  Burke, W.,  Caga-Anan, C. F.,  Chinnaiyan, A. M.,  Chung, W. K.,  Clayton, E. W.,  Cooper, G. M.,  East, K.,  Evans, J. P.,  Fullerton, S. M.,  Garraway, L. A.,  Garrett, J. R.,  Gray, S. W.,  Henderson, G. E.,  Hindorff, L. A.,  Holm, I. A.,  Lewis, M. H.,  Hutter, C. M.,  Janne, P. A.,  Joffe, S.,  Kaufman, D.,  Knoppers, B. M.,  Koenig, B. A.,  Krantz, I. D.,  Manolio, T. A.,  McCullough, L.,  McEwen, J.,  McGuire, A.,  Muzny, D.,  Myers, R. M.,  Nickerson, D. A.,  Ou, J.,  Parsons, D. W.,  Petersen, G. M.,  Plon, S. E.,  Rehm, H. L.,  Roberts, J. S.,  Robinson, D.,  Salama, J. S.,  Scollon, S.,  Sharp, R. R.,  Shirts, B.,  Spinner, N. B.,  Tabor, H. K.,  Tarczy-Hornoch, P.,  Veenstra, D. L.,  Wagle, N.,  Weck, K.,  Wilfond, B. S.,  Wilhelmsen, K.,  Wolf, S. M.,  Wynn, J.,  Yu, J. H.: Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine. Am J Hum Genet 98(6): 1051-66, Jun 2016.

Spinner, N. B.: Cytogenetic highlights and transitions. Am J Med Genet C Semin Med Genet 172(2): 87-91, Jun 2016.

Mouzaki, M., Bass, L. M., Sokol, R. J., Piccoli, D. A., Quammie, C., Loomes, K. M., Heubi, J. E., Hertel, P. M., Scheenstra, R., Furuya, K., Kutsch, E.,  Spinner, N. B., Robbins, K. N., Venkat, V., Rosenthal, P., Beyene, J.,  Baker, A., Kamath, B. M.: Early life predictive markers of liver disease outcome in an International, Multicentre Cohort of children with Alagille syndrome. Liver Int 36(5): 755-60, May 2016.

Bowdin, S.,  Gilbert, A.,  Bedoukian, E.,  Carew, C.,  Adam, M. P.,  Belmont, J.,  Bernhardt, B.,  Biesecker, L.,  Bjornsson, H. T.,  Blitzer, M.,  D'Alessandro, L. C.,  Deardorff, M. A.,  Demmer, L.,  Elliott, A.,  Feldman, G. L.,  Glass, I. A.,  Herman, G.,  Hindorff, L.,  Hisama, F.,  Hudgins, L.,  Innes, A. M.,  Jackson, L.,  Jarvik, G.,  Kim, R.,  Korf, B.,  Ledbetter, D. H.,  Li, M.,  Liston, E.,  Marshall, C.,  Medne, L.,  Meyn, M. S.,  Monfared, N.,  Morton, C.,  Mulvihill, J. J.,  Plon, S. E.,  Rehm, H.,  Roberts, A.,  Shuman, C.,  Spinner, N. B.,  Stavropoulos, D. J.,  Valverde, K.,  Waggoner, D. J.,  Wilkens, A.,  Cohn, R. D.,  Krantz, I. D.: Recommendations for the integration of genomics into clinical practice. Genet Med  May 12 2016 Notes: [Epub ahead of print] Review.

Mulchandani, S., Bhoj, E. J., Luo, M., Powell-Hamilton, N., Jenny, K.,  Gripp, K. W., Elbracht, M., Eggermann, T., Turner, C. L., Temple, I. K., Mackay, D. J., Dubbs, H., Stevenson, D. A., Slattery, L., Zackai, E. H., Spinner, N. B., Krantz, I. D., Conlin, L. K.: Maternal uniparental disomy of chromosome 20: a novel imprinting disorder of growth failure. Genet Med 18(4): 309-15, Apr 2016.

Rajagopalan, R., Grochowski, C. M., Gilbert, M. A., Falsey, A. M., Coleman, K., Romero, R., Loomes, K. M., Piccoli, D. A., Devoto, M., Spinner, N. B.: Compound heterozygous mutations in NEK8 in siblings with end-stage renal disease with hepatic and cardiac anomalies. Am J Med Genet A 170(3): 750-3, Mar 2016.

Izumi, K., Hayashi, D., Grochowski, C.M., Kubota, N., Nishi, E., Arakawa, M., Hiroma, T., Hatata, T., Ogiso, Y., Nakamura, T., Falsey, A. M., Hidaka, E., Spinner, N. B.: Discordant clinical phenotype in monozygotic twins with Alagille syndrome: Possible influence of non-genetic factors. Am J Med Genet A 170(2): 471-5, Feb 2016.

Grochowski, C.M., Loomes, K.M., Spinner, N.B.: Jagged1 (JAG1): Structure, expression, and disease associations. Gene 576(1 Pt 3): 381-4, Jan 15 2016.

2015

Grochowski Christopher M, Loomes Kathleen M, Spinner Nancy B. Jagged1 (JAG1): Structure, expression, and disease associations. Gene. 2016 Jan 15;576(1 Pt 3):381-4. doi: 10.1016/j.gene.2015.10.065. Epub 2015 Nov 6.

Tilib Shamoun S, Le Friec G, Spinner N, Kemper C, Baker AJ. Immune dysregulation in Alagille syndrome: A new feature of the evolving phenotype. Clin Res Hepatol Gastroenterol. 2015 Oct;39(5):566-9. doi: 10.1016/j.clinre.2015.02.003. Epub 2015 May 27.

Reiff M, Giarelli E, Bernhardt BA, Easley E, Spinner NB, Sankar PL, Mulchandani S. Parents' Perceptions of the Usefulness of Chromosomal Microarray Analysis for Children with Autism Spectrum Disorders. J Autism Dev Disord 45(10): 3262-75, Oct 2015.

Izumi K, Hayashi D, Grochowski CM, Kubota N, Nishi E, Arakawa M, Hiroma T, Hatata T, Ogiso Y, Nakamura T, Falsey AM, Hidaka E, Spinner NB. Discordant clinical phenotype in monozygotic twins with Alagille syndrome: Possible influence of non-genetic factors. Am J Med Genet A. 2016 Feb;170(2):471-5. doi: 10.1002/ajmg.a.37429. Epub 2015 Oct 13.

Mulchandani S, Bhoj EJ, Luo M, Powell-Hamilton N, Jenny K,  Gripp KW, Elbracht M, Eggermann T, Turner CL, Temple IK, Mackay DJ, Dubbs H, Stevenson DA, Slattery L, Zackai EH, Spinner NB, Krantz ID, Conlin L.K. Maternal uniparental disomy of chromosome 20: a novel imprinting disorder of growth failure. Genet Med. 2016 Apr;18(4):309-15. doi: 10.1038/gim.2015.103. Epub 2015 Aug 6.

Mouzaki M, Bass LM, Sokol RJ, Piccoli DA, Quammie C, Loomes KM, Heubi JE, Hertel PM, Scheenstra R, Furuya K, Kutsch E, Spinner NB, Robbins KN, Venkat V, Rosenthal P, Beyene J,  Baker, A, Kamath BM. Early life predictive markers of liver disease outcome in an International, Multicentre Cohort of children with Alagille syndrome. Liver Int. 2015 Jul 22. doi: 10.1111/liv.12920. [Epub ahead of print]

Luo M, Mulchandani S, Dubbs HA, Swarr D, Pyle L, Zackai EH, Spinner NB. Conlin LK Detection of mutually exclusive mosaicism in a girl with genotype-phenotype discrepancies. Am J Med Genet A. 2015 Dec;167(12):3091-5. doi: 10.1002/ajmg.a.37261. Epub 2015 Jul 21.

Botkin JR, Belmont JW, Berg JS, Berkman BE, Bombard Y, Holm IA, Levy HP, Ormond KE, Saal HM, Spinner NB. Wilfond, B. S.,  McInerney, J. D.: Points to Consider: Ethical, Legal, and Psychosocial Implications of Genetic Testing in Children and Adolescents. Am J Hum Genet 97(1): 6-21, Jul 2015.

Tsai EA, Grochowski CM, Falsey AM, Rajagopalan R, Wendel D, Devoto M, Krantz ID, Loomes KM, Spinner NB. Heterozygous deletion of FOXA2 segregates with disease in a family with heterotaxy, panhypopituitarism, and biliary atresia. Hum Mutat 36(6): 631-7, Jun 2015.

Grochowski CM, Rajagopalan R, Falsey AM, Loomes KM, Piccoli DA, Krantz ID, Devoto M, Spinner NB. Exome sequencing reveals compound heterozygous mutations in ATP8B1 in a JAG1/NOTCH2 mutation-negative patient with clinically diagnosed Alagille syndrome. Am J Med Genet A 167a(4): 891-3, Apr 2015.

Amendola LM, Dorschner MO, Robertson PD, Salama JS, Hart R, Shirts BH, Murray ML, Tokita MJ, Gallego CJ, Kim DS, Bennett J T, Crosslin DR, Ranchalis J, Jones KL, Rosenthal EA, Jarvik E R, Itsara A, Turner EH, Herman DS, Schleit J, Burt A, Jamal SM, Abrudan JL, Johnson AD, Conlin LK, Dulik MC, Santani A, Metterville DR, Kelly M, Foreman AK, Lee K, Taylor KD, Guo X,  Crooks K, Kiedrowski LA, Raffel L J, Gordon O, Machini K, Desnick R J, Biesecker LG, Lubitz SA, Mulchandani S, Cooper GM, Joffe S, Richards CS, Yang Y, Rotter JI, Rich SS, O'Donnell CJ,  Berg JS, Spinner NB, Evans JP, Fullerton SM, Leppig KA, Bennett RL, Bird T, Sybert VP, Grady WM, Tabor HK, Kim JH, Bamshad MJ, Wilfond B, Motulsky AG, Scott CR, Pritchard CC, Walsh TD,  Burke W, Raskind WH, Byers P, Hisama FM, Rehm H, Nickerson DA, Jarvik GP. Actionable exomic incidental findings in 6503 participants: challenges of variant classification. Genome Res 25(3): 305-15, March 2015.

Baird LC, Smith ER, Ichord R, Piccoli DA, Bernard TJ, Spinner NB, Scott RM, Kamath BM. Moyamoya syndrome associated with Alagille syndrome: outcome after surgical revascularization. J Pediatr 166(2): 470-3, Feb 2015.

2014

Tsai EA, Grochowski CM, Loomes KM, Bessho K, Hakonarson H, Bezerra JA, Russo PA, Haber BA, Spinner NB, Devoto M. Replication of a GWAS signal in a Caucasian population implicates ADD3 in susceptibility to biliary atresia. Hum Genet 133(2): 235-43, 2014.

Salas-Labadia C, Cervantes-Barragan DE, Cruz-Alcivar R, Daber RD, Conlin LK, Leonard LD, Spinner NB, Duran-McKinster C, Davila-Ortiz de Montellano D J, Del Castillo-Ruiz V,  Perez-Vera P. Cytogenomic and phenotypic analysis in low-level monosomy 7 mosaicism with non-supernumerary ring chromosome 7. Am J Med Genet A 164A(7): 1765-9, 2014.

Reiff M, Mueller R, Mulchandani S, Spinner NB, Pyeritz RE, Bernhardt BA. A qualitative study of healthcare providers'' perspectives on the implications of genome-wide testing in pediatric clinical practice. J Genet Couns 23(4): 474-88, 2014.

Ng VL, Haber BH, Magee JC, Miethke A, Murray KF, Michail S, Karpen SJ, Kerkar N, Molleston JP, Romero R, Rosenthal P, Schwarz KB, Shneider BL, Turmelle YP, Alonso EM, Sherker AH,  Sokol RJ, Childhood Liver Disease, Research,  Education, Network. Medical status of 219 children with biliary atresia surviving long-term with their native livers: results from a North American multicenter consortium. J Pediatr 165(3): 539-546 e2, 2014.

Masino AJ, Dechene ET, Dulik MC, Wilkens A, Spinner NB, Krantz ID, Pennington JW, Robinson PN, White PS. Clinical phenotype-based gene prioritization: an initial study using semantic similarity and the human phenotype ontology. BMC Bioinformatics. 2014 Jul 21;15:248. doi: 10.1186/1471-2105-15-248.

Lin H, Zoll B, Russo P, Spinner NB, Loomes KM. A challenging Case of Focal Extrahepatic Duct Obstruction/Hypoplasia in Alagille Syndrome. J Pediatr Gastroenterol Nutr. 2014 Sep 8. [Epub ahead of print]

Leonard LD, Chao G, Baker A, Loomes K, Spinner NB. Clinical utility gene card for: Alagille Syndrome (ALGS). Eur J Hum Genet 22(3), 2014.

Kaur M, Izumi K, Wilkens AB, Chatfield KC, Spinner NB, Conlin LK, Zhang Z, Krantz ID. Genome-wide expression analysis in fibroblast cell lines from probands with Pallister Killian syndrome. PLoS One 9(10): e108853, 2014.

Jarvik GP, Amendola LM, Berg JS, Brothers K, Clayton EW, Chung W, Evans BJ, Evans JP, Fullerton SM, Gallego CJ, Garrison NA, Gray SW, Holm IA, Kullo IJ, Lehmann LS, McCarty C, Prows C A, Rehm HL, Sharp RR, Salama J, Sanderson S, Van Driest SL, Williams MS, Wolf SM, Wolf WA, e, Merge Act- R. O. R. Committee, Cerc Committee, Cser Act-ROR Working Group, Burke W. Return of genomic results to research participants: the floor, the ceiling, and the choices in between. Am J Hum Genet 94(6): 818-26, 2014.

Guilherme RS, Soares KC, Simioni M, Vieira TP, Gil-da-Silva-Lopes VL, Kim CA, Brunoni D, Spinner NB, Conlin LK, Christofolini DM, Kulikowski LD, Steiner CE, Melaragno MI. Clinical, cytogenetic, and molecular characterization of six patients with ring chromosomes 22, including one with concomitant 22q11.2 deletion. Am J Med Genet A 164A(7): 1659-65, 2014.

Ng VL, Haber BH, Magee JC, Miethke A, Murray KF, Michail S, Karpen SJ, Kerkar N, Molleston JP, Romero R., Rosenthal P, Schwarz KB, Shneider BL,Turmelle YP, Alonso EM, Sherker AH, Sokol RJ. Medical status of 219 children with biliary atresia surviving long-term with their native livers: results from a North American multicenter consortium. J Pediatr. 2014 Sep;165(3):539-546.e2. doi: 10.1016/j.jpeds.2014.05.038. Epub 2014 Jul 9.

Jarvik GP, Amendola LM, Berg JS, Brothers K, Clayton EW, Chung W, Evans BJ, Evans JP, Fullerton SM, Gallego CJ, Garrison NA, Gray SW, Holm IA, Kullo IJ, Lehmann LS, McCarty C, Prows CA, Rehm HL, Sharp RR, Salama J, Sanderson S, Van Driest SL, Williams MS, Wolf SM, Wolf WA, Burke W. Return of genomic results to research participants: the floor, the ceiling, and the choices in between. Am J Hum Genet. 2014 Jun 5;94(6):818-26. doi: 10.1016/j.ajhg.2014.04.009. Epub 2014 May 8.

Posters and Presentations

Lectures by Invitation

Spinner NB. Mosaicism Revealed: How Technological Advances are Increasing our Understanding of Mosaicism in Genetic Disorders. National Society of Genetic Counselors 34th Annual Education Conference; 2015 Oct 23; Pittsburgh, PA.

Spinner NB. Cytogenetic Highlights and Transitions. Laird Jackson Festschrift; 2015 Oct 1; Philadelphia, PA.

Spinner NB. Genetic Susceptibility to Biliary Atresia, ChiLDREN Consortium Face to Face Meeting;  2015 Sep; Alexandria, Virginia.

Spinner NB. From Genetics to Genomics: the CHOP experience. Invitae, Corporation; 2015 Jul 30; San Francisco, CA.

Spinner NB. Lost In Translation — From Discovery to Diagnostics of Rare Pediatric Disorders. Harvard Medical School Genetics Training Program; 2015 Apr; Boston, MA.

Spinner NB. The Yield of Exomes for Various Clinical Indications: CSER Experience, Exome Short Course. American College of Medical Genetics Annual Meeting; 2015 Mar; Salt Lake City, Utah.

2014

Spinner NB. Effects of ring chromosomes on phenotype and gene expression. Ring Chromosome 14 Symposium; 2014 Oct; Erbusco, Italy.

Spinner NB. Mosaicism. Shodair Conference on Clinical Genetics; 2014 Jul; Helena, Montana.

Spinner NB. Genomics 101 in the modern era (Pediatric liver disease in the era of genomics). Digestive Disease Week 2014;  2014 May; Chicago, IL.

Spinner NB. Mosaicism. European Society of Human Genetics; 2014 May; Milan, Italy.

Spinner NB. Unexpected consequences of large-scale genetic sequencing. CHOP Responsible Conduct of Research; 2014 Mar.

Spinner NB. Genetic Susceptibility to biliary atresia. Childhood Liver Disease Research and Education Network (ChiLDREN) meeting; 2014 Jan; Baltimore, MD.

Awards and Honors

2011, Evelyn Willing Bromley Endowed Chair in Pediatric Pathology

2009, Faculty Mentor Award, The Children's Hospital of Philadelphia

2004, John Morgan Society, University of Pennsylvania School of Medicine

2002, Ethel Brown Foerderer Fund Fellow

1999, Klaus and Mary Hummeler Endowed Research Prize

1997, Dean's Award for Excellence in Basic Science Teaching, University of Pennsylvania School of Medicine

1997, University of Pennsylvania, Class of 2000, Excellence in Teaching Award

1996, University of Pennsylvania School of Medicine, Class of 1999, Excellence in Teaching Award

1995-1997, Ethel Brown Foerderer Fund Fellow, University of Pennsylvania School of Medicine, Class of 1999 Excellence in Teaching Award

1992-1993, Recipient Florence R.C. Murray Fellowship, University of Pennsylvania School of Medicine

1984-1985, Mary Elizabeth Rennie intramural award for research on epilepsy, University of California, Berkley

1972-1975, Dean's List, Brandeis University

Editorial and Academic Positions

Editorial Positions

2010-present, Associate Editor, PLoS Genetics
2007-present, Circulation Research
2005-present, Communicating Editor, Human Mutation
2002-present, European Journal of Human Genetics
2002-present, Genetics in Medicine
1997-present, Nature Genetics
1997-present, Human Molecular Genetics
1997-present, Molecular Diagnosis
1997-present, Journal of Clinical Investigation
1995-present, New England Journal of Medicine
1994-present, Human Genetics
1991-present, American Journal of Medical Genetics
1989-present, American Journal of Human Genetics

Academic and Institutional Committees

2013-present, Member, Search Committee for Chair, Dept of Genetics, Chair, Nominating Committee, American Society of Human Genetics

2012-present, Member, Nominating Committee, American Society of Human Genetics

2012-present, Provost's Academic Planning and Budget Committee

2008-present, Scientific Advisory Board, Penn Center for the Integration of Genetic Healthcare Technology (PENN CIGHT)

2008-present, Internal Scientific Advisory Board, Center for Molecular studies in Digestive and Liver Disease

2007-present, Institutional Core Advisory Committee, Joseph Stokes Jr. Research Institute

2003-present, Member, Biomedical Graduate Studies Emergency Financial Aid Committee

1998-present, School of Medicine Teaching Awards Selection Committee

Leadership and Memberships

Memberships in Professional Organizations

Alagille Syndrome Alliance (Scientific Advisory Board)
American College of Medical Genetics (Founding Fellow)
American Society of Human Genetics