3/8/2019

Congenital diaphragmatic hernia

• 1 in 3000 births Novel genetic mechanisms of congenital • 8% of all birth defects diaphragmatic hernia • Annual US cost is $158 million • 20%-40% mortality • 40% -50% Non-isolated Wendy Chung, MD PhD Kennedy Family Professor of Pediatrics and Medicine - Up to 25% with CHD Columbia University - Developmental delay/ID common

DHREAMS protocol

• Birth cohort L CDH • Neonates affected with diaphragm defects • Samples from affected case and both biological parents (Trio collection) • Developmental assessments at 2 and 5 years • Retrospective cohort • Children and adults with a personal history of a diaphragm defect • Samples from affected case and both biological parents (Trio collection) • Genetic analysis

Chongqing Three Gorges • Natural history studies Central Hospital

1 3/8/2019

Study protocol Genetic Evidence for CDH • Eligible subjects • Children and fetuses • Familial aggregation • Protocol • Higher rate of concordance in monozygotic v.s. dizygotic twins • Collection of blood from proband and biological parents • Mouse studies elucidated the role of several in • Over 100 data points on prenatal history, NICU stay, surgical report, and family history diaphragm development • Prospective cohort • Coup-TFII, Slit3, Gata4, Fog2, Wt1 • Collection of skin and diaphragm at time of surgery • Pulmonary Hypertension assessment at 1 and 3 months • anomalies (10-30%) • 2 year developmental assessment • T21, T18, T13, tetrasomy12p, 15q26, 8p23.1, 1q41-q42 • Vineland Adaptive Behavior Scale II • • Bayley Scales of Infant Development III Single disorder (15-??%) • 5 year developmental assessment • Donnai-Barrow syndrome (LRP2 2q31), Mathew-Wood syndrome • Vineland Adaptive Behavior Scale II (STRA6 15q24), Denys-Drash (WT1, 11q13) • Child Behavior Check List, Parent and Teacher • GATA6, GATA4, ZFPM2 and others • Wechsler Preschool and Primary Scale of Intelligence IV

Published Current Study Duplication Deletion Deletions of 8p23.1 associated with CDH p15 Translocation/ inversion a 4 3 8p23.1 8p21.2 p12=-3.3

P22.3 9 p23.1 p23.1 5 4 pter-p22 3M 6M 9M12M 15M 18M 21M p21 2 8,043,620 11,883,409 p13 01-0162 192,262 15,227,167 07-0010 7 3 q25-q31.2 q22 4 4 3 3 7,256,229 12,077,383 q31 q22-q23 Wat et al., 2009 [51] 6,504,084 12,752,448 4 2 q41-q42 2 7 4 Slavotinek et al., 2005 [53] q37 q35.2 trisomy q25.3-qter q23.3-q25 q23.3-qter 6,365,021 Chr1 Chr2 Chr3 Chr4 Chr5 Chr6 Chr7 Chr8 Chr9 Chr10 Chr11 12,611,673 Shimokawa et al., 2005 [16] 17,870,612 Faivre et al., 1998 [54] pks p11-13

ERI1 PRSS55 PINX1 CLDN23 TNKS SLC35G5 p13.11-p12.3 RP1L1 FDFT1 SGK223 MFHAS1 XKR6 BLK DEFB135 p12.3 PPP1R3B C8orf74 q12 MTMR9 CTSB MSRA FAM167A GATA4 DEFB136 q11.1-11.21 NEIL2 pter-q11 SOX7 26 q33.3-q34 3 q26 q32-qter trisomy Chr12 Chr13 Chr14 Chr15 Chr16 Chr17 Chr18 Chr19 Chr20 Chr21 trisomy Chr22

2 3/8/2019

GATA4 information p.R252W p.R283H p.N248S p.M247T c.754C>T c.848G>A p.Y244S p.N239S p.N285K p.A411V p.D425N Whole exome sequencing in familial CDH p.S70T p.P87S p.N239D p.R252P p.Q316E p.G234S p.C292R p.S429T p.G69D p.S90R p.R320W p.P407Q p.R229S p.T280M p.A294V p.G64E p.G93A c.755G>C p.G296R p.S52F p.M223T p.K329N p.H436Y p.D95A p.G221R p.I255T p.N273S p.G296S p.H28Y p.G296C p.E359K p.H28D p.S160T p.E216D p.L261P p.T277I p.L403M p.A442V p.G21V p.P163R p.F214S p.C271R p.H302R p.T354A p.G16C p.P163S p.F211L p.V267M p.V380M p.R260Q p.M310V p.A346V p.A6V p.F208L p.R266X

Exon Exon1 Exon2 Exon3 Exon4 Exon6 Exon7 1 Exon5

1 615 616 783 784 909 910 997 998 1146 1147 1329 c.69_374dupTGCCGC c.341_342insA c.677delC c.1074delC c.1075delG c.366_368dupCGC c.139_141delTCC NZnF CZnF GATA GATA

1 206 211 261 265 315 442 p.R252W p.R283H 240 295 Human ACGLYHKMNGI NRPLI KPQRRLSASRRVGLSCANCQTTTTTL WRRNAEGEPVCNAC Chimpanzee ACGLYHKMNGI NRPL I KPQRRL SASRRVGL SCANCQTTTTTL WRRNAEGEPVCNAC Rhesus ACGLYHKMNGI NRPLI KPQRRLSASRRVGLSCANCQTTTTTL WRRNAEGEPVCNAC Mouse ACGLYHKMNGI NRPLI KPQRRLSASRRVGLSCANCQTTTTTL WRRNAEGEPVCNAC Rat ACGLYHKMNGI NRPLI KPQRRLSASRRVGLSCANCQTTTTTL WRRNAEGEPVCNAC Rabbit ACGLYHKMNGI NRPLI KPQRRLSASRRVGLSCANCQTTTTTL WRRNAEGEPVCNAC Dolphin ACGLYHKMNGI NRPLI KPQRRLSASRRVGLSCANCQTTTTTL WRRNAEGEPVCNAC Elephant ACGLYHKMNGI NRPLI KPQRRLSASRRVGLSCANCQTTTTTL WRRNAEGEPVCNAC Opossum ACGLYHKMNGI NRPLI KPQRRLSASRRVGLSCANCQTTTTTL WRRNAEGEPVCNAC Chicken ACGLYHKMNGI NRPLFKPQRRLSASRRVGLSCANCHTTTTTL WRRNAEGEPVCNAC X.tropicalis ACGLYHKMNGI NRPL I KPQRRL SASRRVGL SCANCHTTTTTL WRRNAEGEPVCNAC Zebrafish ACGLYHKMNGI NRPLVKPQRRLSASRRVGLSCTNCQTTTTTL WRRNAEGEPVCNAC

3 3/8/2019

A GATA4 I 1 2 +/+ • A that controls and differentiation in a variety of cell types. • Located at 8p23.1-p22 where there is a recurrent II microdeletion associated with both congenital heart disease and CDH (Wat et al. 2009). 1 +/+ 2 +/+ 3 +/- 4 +/+ • GATA4 is an important component of the retinoic signaling pathway. • ~14% of mice with heterozygous Gata4+/Δex2 had diaphragm III defects and ~36% had cardiac defect. (Jay et al. 2007). 1 2 +/+ 3 4 +/- 5 +/+ • The N-terminal zinc finger of GATA4 interacts with FOG2 during cardiac morphogenesis (Crispino et al. 2001). FOG2 is an important gene in diaphragm development (Ackerman et al. IV 2005). GATA4 c.754 C>T p.R252W genotype 1 +/- 2 +/+

III.4 Father A B III.4 Father Not all Genetic Conditions Run in Families De novo mutations are common in autism, schizophrenia, intellectual disabilities, seizures, birth defects, syndromes

C D

II.3 Grandfather II.3 Grandfather

4 3/8/2019

Number Percent Gender Male 212 58.6% Female 150 41.4% Characteristics CDH classification Types of Genetic Variants of CDH Isolated 208 57.5% Complex 149 41.2% Original DNA code patients Unknown 5 1.4% DHREAMS cohort (n=283): Time of recruitment DNA Bases -> C A G C A G C A G C A G C A G C A G C A G Neonatal 229 80.9% (n=362) Fetal 9 3.2% Amino acids -> Gln Gln Child 45 15.9% Gln Gln Gln Gln Gln Discharge vital status (n=283) Survived 241 85.2% Deceased 42 14.8% Development assessment¶ (n=283) Deleterious missense (D-mis) Likely Gene Disrupting (LGD) At 2 years follow-up 152 53.7% At 5 years follow-up 70 24.7% No assessment at either 2 or 5 years 128 45.2% Additional anomalies in complex cases (n=149) C A G C A G C G G C A G C A G C A G C A G C A G C A G U A G Cardiovascular 66 44.3% § Neurodevelopmental 37 24.8% Gln Gln Arg Gln Gln Gln Gln Gln Gln STOP Skeletal 26 17.4% Genitourinary 14 9.4% Gastrointestinal 13 8.7%

Burden of coding LGD and damaging de novo Higher enrichment of damaging variants in complex variants in CDH patients cases and female cases Number of Baseline Fold Case group Variant class Number of variants Baseline expectation Fold enrichment P-value Gene Sets Variant class P-value variants expectation enrichment Complex Silent 44 44.9 0.98 0.57 Synonymous 110 109.1 1.01 0.48 (n=149) Missense 124 103.1 1.2 0.025 Missense 295 250.6 1.18 3.42E-03 D-mis 62 38.5 1.61 3.08E-04 All Genes LGD 23 13.5 1.7 0.012 D-mis 138 93.7 1.47 1.08E-05 Isolated Silent 63 62.7 1.01 0.5 LGD 57 32.9 1.73 8.60E-05 (n=208) Missense 165 144 1.15 0.046 Synonymous 34 38.8 0.88 0.80 D-mis 74 53.8 1.38 5.22E-03 Constrained Missense 112 88.1 1.27 7.91E-03 LGD 31 18.9 1.64 6.52E-03 Genes D-mis 59 38.0 1.55 9.39E-04 Female Silent 44 45.9 0.96 0.63 LGD 30 12.0 2.50 9.05E-06 (n=150) Missense 118 105.6 1.12 0.12 Synonymous 76 70.3 1.08 0.26 D-mis 64 39.3 1.63 1.85E-04 Missense 184 162.6 1.13 0.053 Other Genes LGD 29 13.9 2.09 2.51E-04 D-mis 80 55.7 1.44 1.28E-03 Male Silent 66 63.2 1.04 0.38 LGD 27 20.9 1.29 0.11 (n=212) Missense 177 145.1 1.22 5.63E-03 D-mis 74 54.3 1.36 6.45E-03 LGD 28 19 1.47 0.032

5 3/8/2019

Genes with recurrent de novo LGD or missense MYRF is a new syndromic CDH gene associated with pulmonary hypertension and pulmonary hypoplasia Sample Genetic De novo variant Diaphragm Study Cardiovascular defect Urogenital defect Other malformations variants ID Sex# (NM_001127392.2) defect c.235dupG: 01-1008 XY L-CDH ASD,VSD,ToF Bilateral undescended testes No p.G81Wfs*45 c.1303G>A:p.G435 No internal genital organs, blind- 01-0429 XX L-CDH VSD Accessory spleen R ending vagina 04-0042 XY c.2036T>C:p.V679A L-CDH ASD,VSD Unknown Unknown (Deceased)

Current c.2084G>A:p.R695 Ambiguous genitalia, undescended Intellectual disability and motor 05-0050 XY CDH HLHS study H testes delay at 2 years old

01-0033 XX R-CDH Scimitar syndrome Unknown Unknown (Deceased) c.1904-1G>A 01-0591* XX Unknown HLHS Unknown Unknown (Deceased) Pulmonary Swyer syndrome with female CHU-11 XY c.1786C>T:p.Q596* Dextrocardia Right pulmonary hypoplasia hypoplasia genitalia Pulmonary Ambiguous genitalia, hypospadias, 1-02264 XY c.1160T>C:p.F387S AAH, CoA, HLHS No hypoplasia undescended testis Right hemi- c.1209G>C:p.Q403 Scimitar syndrome, AAH, PCGC[29] 1-03160 XY diaphragm Undescended testis Lung hypoplasia H ASD, BAV, HLHS, MS, VSD eventration Pulmonary Swyer syndrome with female 1-07403 XY c.1435C>G:p.L479V BAV, CoA Short stature hypoplasia genitalia Penoscrotal hypospadias, Pulmonary Scimitar syndrome, cor Mild speech delay, pulmonary Case 1 XY c.2336+1G>A micropenis, unilateral Pinz et hypoplasia triatriatum hypoplasia, tracheal anomalies cryptorchidism al.[30] Persistent urachus, Undescended Cleft spleen, thymic involution, Case 2 XY c.2518C>T:p.R840* R-CDH Scimitar syndrome testis thyroid fibrosis Ambiguous external genitalia, right Chitayat et Fetus c.1254_1255dupGA: Pulmonary Mild pulmonary hypoplasia, XY HLHS hepato-testicular fusion and left al. [31] case p.T419RfsX14 hypoplasia intestinal malrotation spleno-testicular fusion

MYRF is a membrane-associated transcription factor that plays a role in Genetic Overlap with Other Disorders oligodendrocyte differentiation and myelination

6 3/8/2019

Biological processes involved in CDH Functional groups of genes associated with CDH

Damaging de novo variants are associated with higher mortality Genetic groups based on the type of de novo/rare inherited variants and severe pulmonary hypertension in 647 CDH patients

All CDH Isolated Complex clinical diagnosis (N) de novo SNV (N) de novo CNV (N) rare inherited CNV (N) Dead (%) Alive p-value Dead (%) Alive p-value Dead (%) Alive p-value

LGD in known or (constrained and HDE) genes (25) Group1 27 (29.7%) 64 10 (23.3%) 33 17 (35.4%) 31 Group1 (N=93): Mortality prior to pLI>0.5 (5) hot spot regions (4) Group2 27 (15.2%) 151 9 (7.5%) 111 18 (31.0%) 40 damaging de novo Genetic diagnosis (30) D-mis in known or (constrained and HDE) genes 0.015 0.023 0.51 (13) initial discharge variants Group3 32 (18.1%) 145 18 (14.9%) 103 14 (25%) 42 PD-mis in known genes (16) Severe (%) Mild p-value Severe (%) Mild p-value Severe (%) Mild p-value LGD in any other genes (32) Group2 (N=181): D-mis in other genes (5) Pulmonary Group1 44 (71.0%) 18 21 (77.8%) 6 23 (65.7%) 12 likely damaging de PD-mis in any other genes (125) pLI<0.5 (12) pLI>0.5 (29) hypertension at 1 Group2 72 (51.8%) 670.0033 46 (47.4%) 510.0014 26 (61.9%) 16 0.83 novo variants non-frameshift deletion/insertion (13) month Group3 59 (45.0%) 72 33 (37.9%) 54 26 (59.1%) 18 Group3 (n=181): B-mis/sys (73) Severe (%) Mild p-value Severe (%) Mild p-value Severe (%) Mild p-value without damaging de no de novo SNV (108) novo variants Pulmonary Group1 13 (28.2%) 33 5 (23.8%) 16 8 (32%) 17 hypertension at 3 Group2 19 (17.0%) 930.16 11 (14.5%) 650.57 8 (22.2%) 28 0.37 months Group3 17 (15.6%) 92 11 (15.1%) 62 6 (16.7%) 30

7 3/8/2019

Damaging de novo variants are associated with Damaging de novo variants are associated with short neurodevelopmental delay at 2 and 5 yo in CDH patients stature and lower weight at 5 yo in CDH patients

All CDH Isolated CDH Complex CDH A B N Mean (S.D.) p-value N Mean (S.D.) p-value N Mean (S.D.) p-value Group1 38 -1.06 (1.4) 18 -0.82 (1.6) 20 -1.28 (1.2) Weight at 2yr Group2 97 -0.75 (1.3)0.1 68 -0.85 (1.2)0.1 29 -0.51 (1.6) 0.1 Group3 78 -0.61 (1.1) 53 -0.54 (1.2) 25 -0.78 (1.0) Group1 37 -0.56 (1.6) 17 -0.47 (1.9) 20 -0.64 (1.5) Height at 2yr Group2 94 -0.15 (1.2)0.2 66 -0.14 (1.2)0.4 28 -0.19 (1.2) 0.3 Group3 76 -0.12 (1.7) 51 -0.14 (2.0) 25 -0.06 (1.0) Group1 31 -0.35 (1.5) 14 -0.04 (1.4) 17 -0.60 (1.6) Head size at 2yr Group2 82 0.26 (1.3)0.3 55 0.06 (1.2)0.5 27 0.69 (1.5) 0.02 Group3 61 0.40 (4.3) 38 0.65 (5.4) 23 -0.01 (1.3) Group1 34 -0.64 (0.9) 16 -0.37 (1.0) 18 -0.88 (0.9) Weight/height at 2yr Group2 92 -0.67 (1.4)0.7 65 -0.88 (1.2)0.3 27 -0.19 (1.7) 0.2 Group3 73 -0.73 (1.4) 48 -0.71 (1.4) 25 -0.78 (1.3) Group1 17 -0.78 (1.7) 6 -1.04 (1.2) 11 -0.63 (2.0) Weight at 5yr Group2 41 -0.74 (1.5) 0.05 25 -0.75 (1.1) 0.03 16 -0.72 (2.0) 0.5 Group3 31 0.06 (1.4) 22 0.01 (1.1) 9 0.19 (1.9) Group1 18 -1.02 (1.2) 6 -0.93 (1.0) 12 -1.06 (1.3) Height at 5yr Group2 41 -0.33 (1.2) 0.003 24 -0.29 (0.9) 0.005 17 -0.39 (1.4) 0.4 Group3 28 0.24 (1.2) 20 0.48 (1.1) 8 -0.38 (1.4) Group1 14 -0.13 (1.6) 4 -0.18 (1.2) 10 -0.11 (1.8) Weight/height at 5yr Group2 33 -0.83 (1.3)0.03 20 -0.67 (1.3)0.3 13 -1.07 (1.4) 0.07 Group3 24 0.15 (1.3) 17 -0.08 (1.2) 7 0.70 (1.6)

Damaging de novo variants are associated with Damaging de novo variants are associated with neurodevelopmental delay at 2 yo in CDH patients neurodevelopmental delay 5 yo in CDH patients

All CDH Isolated CDH Complex CDH All CDH Isolated CDH Complex CDH Assessment Domains N Mean (S.D.) p-value N Mean (S.D.) p-value N Mean (S.D.) p-value Group1 32 84.6 (20) 14 85.1 (22) 18 84.1 (19) Assessment Domains N Mean(S.D.) p-value N Mean (S.D.) p-value N Mean (S.D.) p-value Language Group2 91 96.5 (15)0.0006 63 98.4 (13)0.003 28 92.4 (20) 0.2 Group3 68 97.4 (15) 45 99.4 (14) 23 93.6 (16) Wechsler Preschool Group1 12 90.6(15) 5 89.2(17) 7 91.6(16) Bayley Scales of Group1 32 84.8 (17) 14 90.4 (19) 18 80.6 (15) and Primary Scale of Cognitive IQ Group2 33 99.3(15)0.08 21 97.4(15)0.5 12 102.6(15) 0.1 Infant Development Group2 89 95.2 (13)0.0003 63 97.4 (10)0.05 26 89.8 (18) 0.01 Intelligence IV at 5 III at 2 years of age Group3 68 96.7 (14) 45 97.3 (14) 23 95.4 (13) years of age Group3 25 91.6(14) 17 93.0(15) 8 88.5(13) Group1 32 83.5 (19) 14 86.4 (20) 18 81.2 (18) Group1 15 92.5(16) 6 82.7(20) 9 99.1(7) Motor Group2 91 94.4 (14)0.00002 63 97.0 (11)0.003 28 88.4 (17) 0.02 Communication 0.02 0.005 0.4 Group3 68 98.7 (15) 45 100.1 (15) 23 96.1 (14) Group2 39 102.6(12) 24 100.7(10) 15 105.8(14) Group1 40 90.4 (17) 18 92.3 (18) 22 88.8 (16) Group3 35 102.5(12) 22 102.3(13) 13 102.8(12) Communication Group2 111 98.4 (12)0.0009 79 100.8 (9)0.004 32 92.4 (17) 0.2 Group1 15 91.9(17) 6 85.3(21) 9 96.3(14) Group3 88 99.2 (11) 60 100.2 (11) 28 97.0 (12) Daily living skill Group2 39 100.8(10)0.05 24 100.7(9)0.01 15 100.9(11) 0.7 Group1 40 89.0 (17) 18 93.4 (19) 22 85.3 (16) Group3 35 99.3(12) 22 98.9(9) 13 99.8(15) Daily living skill Group2 111 97.3 (14)0.007 79 99.2 (10)0.3 32 92.7 (19) 0.09 Group3 88 98.1 (14) 60 99.1 (13) 28 96.0 (15) Vineland Adaptive Group1 15 91.5(14) 6 81.7(18) 9 98.0(7) Vineland Adaptive Group1 40 87.9 (13) 18 91.8 (14) 22 84.6 (12) Behavior Scale II at 5 Social Group2 39 98.1(8)0.04 24 96.0(7)0.006 15 101.5(8) 0.2 Behavior Scale II at Social Group2 111 94.5 (11)0.01 79 95.8 (9)0.5 32 91.4 (16) 0.06 years of age Group3 35 93.9(8) 22 92.7(8) 13 95.88(9) 2 years of age Group3 88 94.6 (10) 60 95.5 (11) 28 92.8 (8) Group1 15 87.3(17) 6 79.3(18) 9 92.6(16) Group1 40 90.0 (14) 18 93.9 (15) 22 86.7 (13) Motor 0.05 0.003 0.8 Motor Group2 110 96.9 (11)0.006 79 98.5 (10)0.1 31 92.8 (13) 0.08 Group2 39 94.2(11) 24 94.3(10) 15 94.0(13) Group3 88 95.9 (12) 60 96.7 (12) 28 94.0 (10) Group3 34 96.4(10) 22 96.1(8) 12 96.8(13) Group1 40 87.7 (16) 18 91.8 (17) 22 84.3 (14) Group1 15 89.3(16) 6 80.2(20) 9 95.4(10) Adaptive behavior Group2 111 95.9 (12)0.002 79 98.0 (9)0.08 32 90.6 (17) 0.07 Adaptive behavior 0.02 0.002 0.6 Group3 88 96.2 (11) 60 97.2 (12) 28 93.9 (11) Group2 39 98.5(10) 24 97.3(9) 15 100.4(12) Group3 34 97.2(9) 22 96.7(8) 12 98.1(11)

8 3/8/2019

Acknowledgments PI: Wendy Chung Research Coordinators Developmental Specialists Cardiologists/Pulmonologists Funding (>$500) Becca Hernan Christiana Farkouh Usha Krishnan 1X01 HL132366-01 Thank You to the 1200 + DHREAMS Families Surgeons Julia Wynn Annette Zygmunt Eric Austin (p) 1P01HD068250-01 Anketil Abreu Vincent Duron Jennifer Kraszewski Jeff Delaney 1P01HD068250-06A1 Gudrun Aspelund Jennifer Butcher Lorrie S Burkhalter Scott Fletcher R01 HD057036-01A1 Mark Arkovitz (p) Kate Brennan (p) Trish Burns Rob Gajarski CHERUBS Ken Azarow Kerry Miller ACDHO Brian Bucher Mary Dabrowiak (p) Mary Michaeleen Cradock Mark Grady Global CDH Dai Chung (p) Brandy Gonzalez Bob Drongowski Eunice Hahn (p) Breath of Hope Michael Cotton Sheila Horak Teresa Gratton Shelby Kutty Tim Crombleholme Jeannie Kreutzman Barbra Jackson Eric Michelfelder Help4CD Robert Cusick Michelle Knezevich Jolene Johnson Donald Moore (p) National Greek Orthodox Ladies Philoptochos Melissa Denko Cheryl Kornberg Arielle Wilson (p) Erika Rosenzweig Society, Inc. Mahmoud ElFiky Karen Lukas Leah Miller (p) Shannon Nees Howard Needleman Fore Hadley Foundation Kimberly Fischer Julia McKee MGH Mamatha Gowda Tasnim Najaf The Wheeler Foundation Joy Perkins Patricia Donohoe Anthony Hesketh (p) Molecular and Statistical Lab The Vanech Foundation Tracy Perry Mauro Longoni David Kays Patricia Lanzano Larsen Family Min Shi (p) Frances High Przemyslaw Kosinski Jiancheng Guo Brountzas/Kostaridis Jayne Sicard –Su (p) Maria Loscertales Foong Yen Lim Lan Yu Family David McCulley Gentry Wools Liyong Deng Joy Maliackal Poulo Wilke Family Caroline Maloney Jeannie Zuk Charles LeDuc Jessica Kim Henley Family George Mychaliska Connie Keung (p) Jimmy Duoung Caroline Collette Guzman and Padolina Xavier Pompar Yuan Zhang Betty Gilman Julie Moteagudo (p) Family Doug Potoka (p) Christine Schad (p) Yufeng Shen Functional Studies John Pietsch (p) Hongjian Qi Orowitz Family Jessica Schultz (p) Gabrielle Kardon David Schindel Linshan Shang (p) Schwartz Family Kate Ackerman Samuel Soffer Ruth Swedler (p) MGH Team >100 donations from Charles Stolar (p) Okochi Shunpel Patricia Donahoe Xin Sun families of <$500 Amy Wagner Aqsa Schakoor Francis High Brad Warner Caroline Coletti Chen Qiang Mauro Longoni Xie Yi-Min

Questions?

PI: Wendy Chung, [email protected]

9