Susan Guttentag
Last active: 3/4/2020


As a physician scientist, I have always had an interest in the foundations of human disease.  I had the opportunity as a research fellow to work on lung surfactant biology just as surfactant therapy was in the final stages of FDA approval for use in prematurely born infants with lung immaturity.  This great advance in neonatology from the 20thcentury fueled my passion for translating basic science discoveries into solutions for human lung disease.  I also learned that such translation takes time.  It was over 30 years from Mary Ellen Avery’s first paper in 1959 showing that preterm infants dying from lung immaturity had a developmental surfactant deficiency to FDA approval of the first surfactant therapy in 1991.  The explosion of human genomics, basic biology and mouse modeling since then hold great potential to shorten the R&D phase of new life-saving and disease-mitigating therapies for human lung diseases.


My laboratory research focuses on mechanisms of disease in the distal lung, specifically on how alveolar epithelial biology is central to lung injury and effective repair. The foundation of our work is in a rare genetic disorder—Hermansky Pudlak syndrome.  Patients with HPS tend to develop progressive lung injury and disordered repair that result in early death in the 4thto 5thdecades of life.  The HPS genes function as mediators of cellular trafficking, specifically from endosomes to lysosome-related organelles in the surfactant producing alveolar type 2 epithelial cells of the distal lung.  HPS gene defects disrupt the trafficking of membrane proteins to and from lamellar bodies, the surfactant storage organelle, but also have far reaching effects on type 2 cell biology, such as impairing mitochondrial energy production. 


Adaptor protein 3 (AP-3) functions in alveolar type 2 cells: Defects in AP-3 are responsible for HPS type 2 and type 9.  Our current studies and published work have identified membrane proteins that depend on AP-3 to reach the lamellar body in type 2 cells.  Ongoing and potential projects include:

  • Identifying critical targeting motifs that confer AP-3 dependent trafficking of membrane proteins to lamellar bodies.
  • Establishing universal targeting motifs that predict trafficking of membrane proteins from endosomes to lysosome-related organelles in type 2 cells, melanocytes, and megakaryocytes.
  • Determining the impact of disrupted AP-3 function on type 2 cell injury, specifically whether disrupted trafficking results in disrupted lamellar body function versus injury due to disrupted endosomal proteostasis.


BLOC-3 (HPS1 + HPS4) functions in alveolar type 2 cells:  In addition to AP-3, the Biogenesis of Lysosome-related Organelle (BLOC) complexes are the functional units of HPS.  BLOC-3 is a heterodimer of HPS1 and HPS4 proteins, and act as a guanine-nucleotide exchange factor for the Rab32/38 family of Rab proteins.  We have demonstrated that loss of BLOC-3 in type 2 cells fails to localize Rab38 to lamellar bodies.  Ongoing and potential projects include:

  • Identifying key proteins in type 2 cells that are specifically targeted to or from lamellar bodies using BLOC-3.
  • Examining the impact of BLOC-3 loss on type 2 cell metabolism, specifically mitochondrial function.
  • Clarifying the role of BLOC-3 on autophagy in type 2 cells.


BLOC-1 functions in alveolar type 2 cells:  Human mutations in BLOC-1 genes are extremely rare but have been associated with interstitial lung disease, an indicator of lung injury and precursor of pulmonary fibrosis.  In melanosomes, BLOC-1 fosters tubular contacts between endosomes and melanosomes that transfer membrane proteins.  We have developed a BLOC-1 defective cell line to model BLOC-1 loss in type 2 cells. Ongoing and potential projects include:

  • Identifying type 2 cell proteins relying on tubular transfer from endosomes to lamellar bodies in type 2 cells
  • Determining the impact of disrupted BLOC-1 function on type 2 cell injury, specifically whether disrupted trafficking results in disrupted lamellar body function versus injury due to disrupted endosomal proteostasis.


We use primary alveolar type 2 cells and cell lines modeling type 2 cells with a variety of techniques (RNAi, CRISPR, mutagenesis, transfection) to model gain- and loss-of-function in vitro. We use mouse models of HPS to examine the impact of HPS protein loss of function on lung disease.  We have access to iPSC from patients with HPS and protocols for differentiating iPSC to alveolar type 2 cells.



The following timeline graph is generated from all co-authored publications.

Featured publications are shown below:

  1. Gene-edited MLE-15 Cells as a Model for the Hermansky-Pudlak Syndromes. Kook S, Qi A, Wang P, Meng S, Gulleman P, Young LR, Guttentag SH (2018) Am J Respir Cell Mol Biol 58(5): 566-574
    › Primary publication · 29190429 (PubMed) · PMC5946333 (PubMed Central)
  2. A nonaggregating surfactant protein C mutant is misdirected to early endosomes and disrupts phospholipid recycling. Beers MF, Hawkins A, Maguire JA, Kotorashvili A, Zhao M, Newitt JL, Ding W, Russo S, Guttentag S, Gonzales L, Mulugeta S (2011) Traffic 12(9): 1196-210
    › Primary publication · 21707890 (PubMed) · PMC3155663 (PubMed Central)
  3. Early alveolar epithelial dysfunction promotes lung inflammation in a mouse model of Hermansky-Pudlak syndrome. Atochina-Vasserman EN, Bates SR, Zhang P, Abramova H, Zhang Z, Gonzales L, Tao JQ, Gochuico BR, Gahl W, Guo CJ, Gow AJ, Beers MF, Guttentag S (2011) Am J Respir Crit Care Med 184(4): 449-58
    › Primary publication · 21616998 (PubMed) · PMC3175543 (PubMed Central)
  4. ERp29 regulates DeltaF508 and wild-type cystic fibrosis transmembrane conductance regulator (CFTR) trafficking to the plasma membrane in cystic fibrosis (CF) and non-CF epithelial cells. Suaud L, Miller K, Alvey L, Yan W, Robay A, Kebler C, Kreindler JL, Guttentag S, Hubbard MJ, Rubenstein RC (2011) J Biol Chem 286(24): 21239-53
    › Primary publication · 21525008 (PubMed) · PMC3122184 (PubMed Central)
  5. Organization of Neonatal Training Program Directors Council responds to the ACGME 2010 Proposed Standards. Ryan RM, Brion LP, Aucott SW, Juul SE, Parker TA, Savich RD, Dukhovny D, Cummings JJ, Guttentag SH, LaGamma EF, Price WA, Campbell DE (2011) J Perinatol 31(4): 296-7
    › Primary publication · 21448184 (PubMed)
  6. IL-17A and TNF-α exert synergistic effects on expression of CXCL5 by alveolar type II cells in vivo and in vitro. Liu Y, Mei J, Gonzales L, Yang G, Dai N, Wang P, Zhang P, Favara M, Malcolm KC, Guttentag S, Worthen GS (2011) J Immunol 186(5): 3197-205
    › Primary publication · 21282514 (PubMed)
  7. The Rho pathway mediates transition to an alveolar type I cell phenotype during static stretch of alveolar type II cells. Foster CD, Varghese LS, Gonzales LW, Margulies SS, Guttentag SH (2010) Pediatr Res 67(6): 585-90
    › Primary publication · 20220547 (PubMed) · PMC3063400 (PubMed Central)
  8. Opposing regulation of human alveolar type II cell differentiation by nitric oxide and hyperoxia. Johnston LC, Gonzales LW, Lightfoot RT, Guttentag SH, Ischiropoulos H (2010) Pediatr Res 67(5): 521-5
    › Primary publication · 20098340 (PubMed) · PMC3066065 (PubMed Central)
  9. Anterograde transport of surfactant protein C proprotein to distal processing compartments requires PPDY-mediated association with Nedd4 ubiquitin ligases. Kotorashvili A, Russo SJ, Mulugeta S, Guttentag S, Beers MF (2009) J Biol Chem 284(24): 16667-16678
    › Primary publication · 19366705 (PubMed) · PMC2713532 (PubMed Central)
  10. Resident duty hour restrictions: is less really more? Brion LP, Neu J, Adamkin D, Bancalari E, Cummings J, Guttentag S, Juul S, Norwood VF, Ryan RM (2009) J Pediatr 154(5): 631-632.e1
    › Primary publication · 19364553 (PubMed)
  11. Posttranslational regulation of surfactant protein B expression. Guttentag S (2008) Semin Perinatol 32(5): 367-70
    › Primary publication · 18929160 (PubMed) · PMC2586979 (PubMed Central)
  12. Developmental and genetic regulation of human surfactant protein B in vivo. Hamvas A, Heins HB, Guttentag SH, Wegner DJ, Trusgnich MA, Bennet KW, Yang P, Carlson CS, An P, Cole FS (2009) Neonatology 95(2): 117-24
    › Primary publication · 18776725 (PubMed) · PMC2765709 (PubMed Central)
  13. Pepsinogen C proteolytic processing of surfactant protein B. Gerson KD, Foster CD, Zhang P, Zhang Z, Rosenblatt MM, Guttentag SH (2008) J Biol Chem 283(16): 10330-8
    › Primary publication · 18256027 (PubMed) · PMC2447652 (PubMed Central)
  14. In vitro transdifferentiation of human fetal type II cells toward a type I-like cell. Foster CD, Varghese LS, Skalina RB, Gonzales LW, Guttentag SH (2007) Pediatr Res 61(4): 404-9
    › Primary publication · 17515862 (PubMed) · PMC3074248 (PubMed Central)
  15. Gene induction during differentiation of human pulmonary type II cells in vitro. Wade KC, Guttentag SH, Gonzales LW, Maschhoff KL, Gonzales J, Kolla V, Singhal S, Ballard PL (2006) Am J Respir Cell Mol Biol 34(6): 727-37
    › Primary publication · 16474099 (PubMed) · PMC2644235 (PubMed Central)
  16. Expression profiles of hydrophobic surfactant proteins in children with diffuse chronic lung disease. Griese M, Schumacher S, Tredano M, Steinecker M, Braun A, Guttentag S, Beers MF, Bahuau M (2005) Respir Res : 80
    › Primary publication · 16042774 (PubMed) · PMC1224872 (PubMed Central)
  17. Wnt/beta-catenin signaling acts upstream of N-myc, BMP4, and FGF signaling to regulate proximal-distal patterning in the lung. Shu W, Guttentag S, Wang Z, Andl T, Ballard P, Lu MM, Piccolo S, Birchmeier W, Whitsett JA, Millar SE, Morrisey EE (2005) Dev Biol 283(1): 226-39
    › Primary publication · 15907834 (PubMed)
  18. Defective surfactant secretion in a mouse model of Hermansky-Pudlak syndrome. Guttentag SH, Akhtar A, Tao JQ, Atochina E, Rusiniak ME, Swank RT, Bates SR (2005) Am J Respir Cell Mol Biol 33(1): 14-21
    › Primary publication · 15790974 (PubMed) · PMC2715302 (PubMed Central)
  19. Surfactant proteins in pulmonary alveolar proteinosis in adults. Brasch F, Birzele J, Ochs M, Guttentag SH, Schoch OD, Boehler A, Beers MF, Müller KM, Hawgood S, Johnen G (2004) Eur Respir J 24(3): 426-35
    › Primary publication · 15358702 (PubMed)
  20. Developmental regulation of claudin localization by fetal alveolar epithelial cells. Daugherty BL, Mateescu M, Patel AS, Wade K, Kimura S, Gonzales LW, Guttentag S, Ballard PL, Koval M (2004) Am J Physiol Lung Cell Mol Physiol 287(6): L1266-73
    › Primary publication · 15347569 (PubMed)
  21. Pepsinogen C: a type 2 cell-specific protease. Foster C, Aktar A, Kopf D, Zhang P, Guttentag S (2004) Am J Physiol Lung Cell Mol Physiol 286(2): L382-7
    › Primary publication · 14578117 (PubMed)
  22. Involvement of napsin A in the C- and N-terminal processing of surfactant protein B in type-II pneumocytes of the human lung. Brasch F, Ochs M, Kahne T, Guttentag S, Schauer-Vukasinovic V, Derrick M, Johnen G, Kapp N, Muller KM, Richter J, Giller T, Hawgood S, Buhling F (2003) J Biol Chem 278(49): 49006-14
    › Primary publication · 13129928 (PubMed)
  23. Surfactant protein B in type II pneumocytes and intra-alveolar surfactant forms of human lungs. Brasch F, Johnen G, Winn-Brasch A, Guttentag SH, Schmiedl A, Kapp N, Suzuki Y, Müller KM, Richter J, Hawgood S, Ochs M (2004) Am J Respir Cell Mol Biol 30(4): 449-58
    › Primary publication · 12972403 (PubMed)
  24. Surfactant protein A and B genetic variants in respiratory distress syndrome in singletons and twins. Marttila R, Haataja R, Guttentag S, Hallman M (2003) Am J Respir Crit Care Med 168(10): 1216-22
    › Primary publication · 12947025 (PubMed)
  25. In vitro surfactant protein B deficiency inhibits lamellar body formation. Foster CD, Zhang PX, Gonzales LW, Guttentag SH (2003) Am J Respir Cell Mol Biol 29(2): 259-66
    › Primary publication · 12649122 (PubMed)
  26. Cysteine protease activity is required for surfactant protein B processing and lamellar body genesis. Guttentag S, Robinson L, Zhang P, Brasch F, Bühling F, Beers M (2003) Am J Respir Cell Mol Biol 28(1): 69-79
    › Primary publication · 12495934 (PubMed)
  27. Differentiation of human pulmonary type II cells in vitro by glucocorticoid plus cAMP. Gonzales LW, Guttentag SH, Wade KC, Postle AD, Ballard PL (2002) Am J Physiol Lung Cell Mol Physiol 283(5): L940-51
    › Primary publication · 12376347 (PubMed)
  28. Differences in N-linked glycosylation between human surfactant protein-B variants of the C or T allele at the single-nucleotide polymorphism at position 1580: implications for disease. Wang G, Christensen ND, Wigdahl B, Guttentag SH, Floros J (2003) Biochem J 369(Pt 1): 179-84
    › Primary publication · 12356334 (PubMed) · PMC1223069 (PubMed Central)
  29. Notch1 and Jagged1 expression by the developing pulmonary vasculature. Taichman DB, Loomes KM, Schachtner SK, Guttentag S, Vu C, Williams P, Oakey RJ, Baldwin HS (2002) Dev Dyn 225(2): 166-75
    › Primary publication · 12242716 (PubMed)
  30. Ascorbic-acid transporter Slc23a1 is essential for vitamin C transport into the brain and for perinatal survival. Sotiriou S, Gispert S, Cheng J, Wang Y, Chen A, Hoogstraten-Miller S, Miller GF, Kwon O, Levine M, Guttentag SH, Nussbaum RL (2002) Nat Med 8(5): 514-7
    › Primary publication · 11984597 (PubMed)
  31. Maintenance of differentiated function of the surfactant system in human fetal lung type II epithelial cells cultured on plastic. Gonzales LW, Angampalli S, Guttentag SH, Beers MF, Feinstein SI, Matlapudi A, Ballard PL (2001) Pediatr Pathol Mol Med 20(5): 387-412
    › Primary publication · 11552739 (PubMed)
  32. Respiratory distress after intratracheal bleomycin: selective deficiency of surfactant proteins B and C. Savani RC, Godinez RI, Godinez MH, Wentz E, Zaman A, Cui Z, Pooler PM, Guttentag SH, Beers MF, Gonzales LW, Ballard PL (2001) Am J Physiol Lung Cell Mol Physiol 281(3): L685-96
    › Primary publication · 11504697 (PubMed)
  33. Prolonged survival in hereditary surfactant protein B (SP-B) deficiency associated with a novel splicing mutation. Dunbar AE, Wert SE, Ikegami M, Whitsett JA, Hamvas A, White FV, Piedboeuf B, Jobin C, Guttentag S, Nogee LM (2000) Pediatr Res 48(3): 275-82
    › Primary publication · 10960490 (PubMed)
  34. Intracellular localization of processing events in human surfactant protein B biosynthesis. Korimilli A, Gonzales LW, Guttentag SH (2000) J Biol Chem 275(12): 8672-9
    › Primary publication · 10722708 (PubMed)
  35. Pulmonary surfactant metabolism in infants lacking surfactant protein B. Beers MF, Hamvas A, Moxley MA, Gonzales LW, Guttentag SH, Solarin KO, Longmore WJ, Nogee LM, Ballard PL (2000) Am J Respir Cell Mol Biol 22(3): 380-91
    › Primary publication · 10696076 (PubMed)
  36. TGF-beta1 inhibits surfactant component expression and epithelial cell maturation in cultured human fetal lung. Beers MF, Solarin KO, Guttentag SH, Rosenbloom J, Kormilli A, Gonzales LW, Ballard PL (1998) Am J Physiol 275(5): L950-60
    › Primary publication · 9815113 (PubMed)
  37. Surfactant protein B processing in human fetal lung. Guttentag SH, Beers MF, Bieler BM, Ballard PL (1998) Am J Physiol 275(3): L559-66
    › Primary publication · 9728051 (PubMed)
  38. Targeting type II and Clara cells for adenovirus-mediated gene transfer using the surfactant protein B promoter. Strayer MS, Guttentag SH, Ballard PL (1998) Am J Respir Cell Mol Biol 18(1): 1-11
    › Primary publication · 9448040 (PubMed)
  39. Expression and glucocorticoid regulation of surfactant protein C in human fetal lung. Solarin KO, Ballard PL, Guttentag SH, Lomax CA, Beers MF (1997) Pediatr Res 42(3): 356-64
    › Primary publication · 9284277 (PubMed)
  40. Arthrogryposis multiplex congenita with posterior column degeneration and peripheral neuropathy: a case report. Folkerth RD, Guttentag SH, Kupsky WJ, Kinney HC (1993) Clin Neuropathol 12(1): 25-33
    › Primary publication · 8382571 (PubMed)
  41. Sepsis with coagulase-negative staphylococci in critically ill newborns. Baumgart S, Hall SE, Campos JM, Polin RA (1983) Am J Dis Child 137(5): 461-3
    › Primary publication · 6846275 (PubMed)
  42. Pediatric acquired immunodeficiency syndrome with negative human immunodeficiency virus antibody response by enzyme-linked immunosorbent assay and Western blot. Goetz DW, Hall SE, Harbison RW, Reid MJ (1988) Pediatrics 81(3): 356-9
    › Primary publication · 2449652 (PubMed)
  43. Surfactant protein regulation and diabetic pregnancy. Guttentag SH, Phelps DS, Floros J (1992) Semin Perinatol 16(2): 122-9
    › Primary publication · 1636126 (PubMed)
  44. Surfactant protein A expression is delayed in fetuses of streptozotocin-treated rats. Guttentag SH, Phelps DS, Stenzel W, Warshaw JB, Floros J (1992) Am J Physiol 262(4 Pt 1): L489-94
    › Primary publication · 1533098 (PubMed)
  45. Delayed hydrophobic surfactant protein (SP-B, SP-C) expression in fetuses of streptozotocin-treated rats. Guttentag SH, Phelps DS, Warshaw JB, Floros J (1992) Am J Respir Cell Mol Biol 7(2): 190-7
    › Primary publication · 1386745 (PubMed)