The lab’s overarching goal is to understand how innate immune pathways in Neutrophils and Platelets, and Extracellular Vesicle (EV)-dependent intercellular communication promote

1. Pulmonary thrombo-inflammation and Acute Chest Syndrome in Sickle Cell Disease.
2. Joint-damage in Hemophilia.
3. Cigarette smoke induced flu severity

Techniques and and approaches used in lab:

1. Multi-Photon-Excitation fluorescence intravital (in vivo) microscopy of thrombo-inflammation in live mice.
2. Ex vivo microfluidic studies with patient blood.
3. Characterization and isolation of extracellular vesicles.
4. Knock-in humanized and fluorescent reporter mice of hematological diseases.
5. Genomics and transcriptomics.

NHLBI 2R01 HL128297 ” Pulmonary arteriole occlusion by platelet-neutrophil micro-emboli in Acute Chest Syndrome”. Role: Contact PI (2015 – 2025)

NHLBI 1R01 HL141080 “Mechanisms of Platelet Exosome-Mediated Acute Chest Syndrome in Sickle Cell Disease”. Role: Contact PI (2019 – 2024)

NHLBI 1R01 HL166345 “CD39-carrying extracellular vesicles regulate pulmonary thrombosis in Sickle Cell Disease”. Role: Contact PI (2023-2027)

American Heart Association 23TPA1074022 “Thrombo-inflammation in cigarette smoke-induced flu severity”. Role: Contact PI (2023-2026)

CSL Behring Inc Research Acceleration Initiative. Role: Contact PI (2021-2026)

Click here for a full list of publications from Prithu Sundd, PhD.

Selected publications:

1. Pai A, Sundd P, Tees DF. In situ Microrheological Determination of Neutrophil Stiffening Following Adhesion in a Model Capillary. Ann Biomed Eng. 2008;36(4):596-603. PubMed PMID: 18214680.   
2. Sundd P, Zou X, Goetz DJ, Tees DF. Leukocyte adhesion in capillary-sized, P-selectin-coated micropipettes. Microcirculation. 2008;15(2):109-122. PubMed PMID: 17952800.
3. Sundd P, Gutierrez E, Pospieszalska MK, Zhang H, Groisman A, Ley K. Quantitative dynamic footprinting microscopy reveals mechanisms of neutrophil rolling. Nature Methods. 2010;7(10):821-824. PubMed PMID: 20871617; PubMed Central PMCID: PMC2967732. Images from this study were on the cover page of the October, 2010 issue of Nature Methods.
4. Gutierrez E, Tkachenko E, Besser A, Sundd P, Ley K, Danuser G, Ginsberg MH, Groisman A. High refractive index silicone gels for simultaneous total internal reflection fluorescence and traction force microscopy of adherent cells. PLoS One. 2011;6(9):e23807. PubMed PMID: 21961031; PubMed Central PMCID: PMC3178539.
5. Sundd P, Gutierrez E, Petrich BG, Ginsberg MH, Groisman A, Ley K. Live cell imaging of paxillin in rolling neutrophils by dual-color quantitative dynamic footprinting. Microcirculation. 2011;18(5):361-372. PubMed PMID: 21418380; PubMed Central PMCID: PMC3123727. Images from this study were on the cover page of the July, 2011 issue of Microcirculation. 
6. Sundd P, Gutierrez E, Koltsova EK, Kuwano Y, Fukuda S, Pospieszalska MK, Groisman A, Ley K. 'Slings' enable neutrophil rolling at high shear. Nature. 2012;488(7411):399-403. PubMed PMID: 22763437; PubMed Central PMCID: PMC3433404.
7. Stadtmann A, Germena G, Block H, Boras M, Rossaint J, Sundd P, Lefort C, Fisher CI, Buscher K, Gelschefarth B, Urzainqui A, Gerke V, Ley K, Zarbock A. The PSGL-1-L-selectin signaling complex regulates neutrophil adhesion under flow. Journal of Experimental Medicine. 2013;210(11):2171-2180. PubMed PMID: 24127491; PubMed Central PMCID: PMC3804951.
8. Koltsova EK, Sundd P, Zarpellon A, Ouyang H, Mikulski Z, Zampolli A, Ruggeri ZM, Ley K. Genetic deletion of platelet glycoprotein Ibα but not its extracellular domain protects from atherosclerosis. Thromb Haemost. 2014;112(6):1252-1263. PubMed PMID: 25104056; PubMed Central PMCID: PMC4429870.
9. Bennewitz MF, Watkins SC, Sundd P. Quantitative intravital two-photon excitation microscopy reveals absence of pulmonary vaso-occlusion in unchallenged Sickle Cell Disease mice. Intravital. 2014;3(2):e29748. PubMed PMID: 25995970; PubMed Central PMCID: PMC4435611.
10. Jimenez MA, Tutuncuoglu E, Barge S, Novelli EM, Sundd P. Quantitative microfluidic fluorescence microscopy to study vaso-occlusion in sickle cell disease. Haematologica. 2015;100(10):e390-393. PubMed PMID: 25975836; PubMed Central PMCID: PMC4591772.
11. Bennewitz MF†, Jimenez MA†, Vats R, Tutuncuoglu E, Jonassaint J, Kato GJ, Gladwin MT, Sundd P. Lung vaso-occlusion in sickle cell disease mediated by arteriolar neutrophil-platelet microemboli. Journal of Clinical Investigation Insight. 2017;2(1):e89761. PubMed PMID: 28097236; PubMed Central PMCID: PMC5214368. †Co-first authors.
12. Jimenez MA, Novelli E, Shaw GD, Sundd P. Glycoprotein Ibα inhibitor (CCP-224) prevents neutrophil-platelet aggregation in Sickle Cell Disease. Blood Advances. 2017;1(20):1712-1716. PubMed PMID: 28966995; PubMed Central PMCID: PMC5617353. Images from this study were on the cover page of the September 12 issue of Blood Advances. 
13. Pradhan-Sundd T, Zhou L, Vats R, Jiang A, Molina L, Singh S, Poddar M, Russell JM, Stolz DB, Oertel M, Apte U, Watkins S, Ranganathan S, Nejak-Bowen KN, Sundd P, Pal Monga S. Dual catenin loss in murine liver causes tight junctional deregulation and progressive intrahepatic cholestasis. Hepatology. 2018 Jun;67(6):2320-2337. doi: 10.1002/hep.29585. PubMed PMID: 29023813; PubMed Central PMCID: PMC5893443.
14. Lendermon EA, Dodd-O JM, Coon TA, Wang X, Ensor CR, Cardenes N, Koodray CL, Heusey HL, Bennewitz MF, Sundd P, Bullock GC, Popescu I, Guo L, O'Donnell CP, Rojas M, McDyer JF. Azithromycin Fails to Prevent Accelerated Airway Obliteration in T-bet-/- Mouse Lung Allograft Recipients. Transplant Proc. 2018 Jun;50(5):1566-1574. PubMed PMID: 29880387.
15. Pradhan-Sundd T, Vats R, Russell JM, Singh S, Michael AA, Molina L, Kakar S, Cornuet P, Poddar M, Watkins SC, Nejak-Bowen KN, Monga SP and Sundd P. Dysregulated bile transporters and impaired tight junctions during chronic liver injury in mice. Gastroenterology. 2018 Oct;155(4):1218-1232.e24. PubMed PMID: 29964040; PubMed Central PMCID: PMC6174089.
16. Li ZG, Scott MJ, Brzóska T, Sundd P, Li YH, Billiar TR, Wilson MA, Wang P, Fan J. Lung epithelial cell-derived IL-25 negatively regulates LPS-induced exosome release from macrophages. Mil Med Res. 2018 Jul 30;5(1):24. PubMed PMID: 30056803; PubMed Central PMCID: PMC6065058.
17. Fatkhullina AR, Peshkova IO, Dzutsev A, Aghayev T, McCulloch JA, Thovarai V, Badger JH, Vats R, Sundd P, Tang HY, Kossenkov AV, Hazen SL, Trinchieri G, Grivennikov SI, Koltsova EK. An Interleukin-23-Interleukin-22 Axis Regulates Intestinal Microbial Homeostasis to Protect from Diet-Induced Atherosclerosis. Immunity. 2018 Nov 20;49(5):943-957.e9. PubMed PMID: 30389414; PubMed Central PMCID: PMC6257980.
18. Voic H, Li X, Jang JH, Zou C, Sundd P, Alder J, Rojas M, Chandra D, Randell S, Mallampalli RK, Tesfaigzi Y, Ryba T, Nyunoya T. RNA sequencing identifies common pathways between cigarette smoke exposure and replicative senescence in human airway epithelia. BMC Genomics. 2019 Jan 9;20(1):22. PubMed PMID: 30626320; PubMed Central PMCID: PMC6325884. 
19. Vats R†, Brzoska T†, Bennewitz MF†, Jimenez MA†, Pradhan-Sundd T, Tutuncuoglu E, Jonassaint J, Gutierrez E, Watkins SC, Shiva S, Scott M, Morelli AE, Neal MD, Kato GJ, Gladwin MT, Sundd P. Platelet extracellular vesicles drive inflammasome-IL1β-dependent lung injury in Sickle Cell Disease. Am J Respir Crit Care Med. 2020 Jan 1;201(1):33-46. PubMed PMID: 31498653; PubMed Central PMCID: PMC6938158. †Co-first authors. 
20. Dyer MR, Alexander W, Hassoune A, Chen Q, Alvikas J, Liu Y, Haldeman S, Plautz W, Loughran P, Li H, Boone B, Sadovsky Y, Sundd P, Zuckerbraun BS, Neal MD. Platelet-derived extracellular vesicles released after trauma promote hemostasis but contribute to DVT in mice. 2019. J Thromb Haemost. 2019 Oct;17(10):1733-1745. PubMed PMID: 31294514; PubMed Central PMCID: PMC6773503. 
21. Pradhan‐Sundd T, Kosar K, Saggi H, Zhang R, Vats R, Cornuet P, Green S, Singh S, Zeng G, Sundd P, Nejak-Bowen K. Wnt/β-catenin signaling plays a protective role in the mdr2 ko murine model of cholestatic liver disease. Hepatology. 2019 Sep 6. doi: 10.1002/hep.30927. PubMed PMID: 31489648. 
22. Bennewitz MF, Tutuncuoglu E, Gudapati S, Brzoska T, Watkins SC, Monga SP, Pradhan-Sundd T, Sundd P. P-selectin deficient mice to study pathophysiology of Sickle Cell Disease. Blood Adv. 2020 Jan 28;4(2):266-273. PubMed PMID: 31968076; PubMed Central PMCID: PMC6988409. Images from this study were on the cover page of the January 28 issue of Blood Advances.
23. Mallampalli RK, Li X, Jang JH, Kaminski T, Hoji A, Coon T, Chandra D, Welty S, Teng Y, Ihle J, Sembrat J, Rojas M, Lafyatis R, Zou C, Sciurba F, Sundd P, Lan L, Nyunoya T. Cigarette Smoke Exposure Enhances Transforming Acidic Coiled-Coil-Containing Protein 2 (TACC2) Turnover and therby Promotes Emphysema. JCI Insight. 2020 Jan 30;5(2). pii: 125895. PubMed PMID: 31996486. PubMed Central PMCID: PMC7098723.
24. Sparkenbaugh EM, Chen C, Brzoska T, Nguyen J, Wang S, Vercellotti GM, Key NS, Sundd P, Belcher JD, Pawlinski R. Thrombin-mediated activation of PAR-1 contributes to microvascular stasis in mouse models of sickle cell disease. Blood. 2020 Jan 23. pii: blood.2019003543. doi: 10.1182/blood.2019003543. PubMed PMID: 31977004. 
25. Vats R, Liu S, Zhu J, Mukhi D, Tutuncuoglu E, Cardenes N, Singh S, Brzoska T, Kosar K, Bamne M, Jonassaint J, Adebayo Michael A, Watkins SC, Hillery C, Ma X, Nejak-Bowen K, Rojas M, Gladwin MT, Kato GJ, Ramakrishnan S, Sundd P, Pal Monga S, Pradhan-Sundd T. Impaired bile acid secretion promotes hepatobiliary injury in Sickle Cell Disease. Hepatology 2020 Mar 19. doi: 10.1002/hep.31239. PubMed PMID: 32190913.
26. Vats R, Tutuncuoglu E, Pradhan-Sundd T, Tejero J, Shaw GD, Sundd P. Tandem P-selectin glycoprotein ligand immunoglobulin (TSGL-Ig) prevents lung vaso-occlusion in Sickle Cell Disease mice. Experimental Hematology. 2020 Apr;84:1-6.e1. doi: 10.1016/j.exphem.2020.03.002. PubMed PMID: 32243995. PubMed Central PMCID: PMC7237323.
27. Brzoska T, Vats R, Bennewitz MF, Tutuncuoglu E, Watkins SC, Ragni MV, Neal MD, Gladwin MT, Sundd P. Intravascular hemolysis triggers ADP-mediated generation of platelet-rich thrombi in pre-capillary pulmonary arterioles. Journal of Clinical Investigation-Insight. 2020 Jul 23;5(14). doi: 10.1172/jci.insight.139437. PubMed PMID: 32544100; PubMed Central PMCID: PMC7453902.
28. Zhao J, Florentin J, Tai YY, Torrino S, Ohayon L, Brzoska T, Tang Y, Yang J, Negi V, Woodcock CC, Risbano MG, Nouraie SM, Sundd P, Bertero T, Dutta P, Chan SY. Long Range Endocrine Delivery of Circulating miR-210 to Endothelium Promotes Pulmonary Hypertension. Circ Res. 2020 Aug 14;127(5):677-692. doi: 10.1161/CIRCRESAHA.119.316398. Epub 2020 Jun 4. PubMed PMID: 32493166; PubMed Central PMCID: PMC7429300.
29. Perkins LA, Nyiranshuti L, Little-Ihrig L, Latoche JD, Day KE, Zhu Q, Tavakoli S, Sundd P, Novelli EM, Anderson CJ. Integrin VLA-4 as a PET imaging biomarker of hyper-adhesion in transgenic sickle mice. Blood Adv. 2020 Sep 8;4(17):4102-4112. doi: 10.1182/bloodadvances.2020002642. PubMed PMID: 32882004; PubMed Central PMCID: PMC7479956.
30. Crompton D, Vats R, Pradhan-Sundd T, Sundd P, Kameneva MV. Drag-reducing polymers improve hepatic vaso-occlusion in SCD mice. Blood Adv. 2020 Sep 22;4(18):4333-4336. doi: 10.1182/bloodadvances.2020002779. PubMed PMID: 32915976; PubMed Central PMCID: PMC7509886.
31. Vats R, Kaminski TW, Ju EM, Brzoska T, Tutuncuoglu E, Tejero J, Novelli EM, Sundd P*, Pradhan-Sundd T.  P-selectin deficiency promotes liver senescence in sickle cell disease mice. Blood. 2021 May 13;137(19):2676-2680. doi:10.1182/blood.2020009779. PubMed PMID:33619560. *Co-corresponding author. 
32. Li X, Noell G, Tabib T, Gregory AD, Trejo Bittar HE, Vats R, Kaminski TW, Sembrat J, Snyder ME, Chandra D, Chen K, Zou C, Zhang Y, Sundd P, McDyer JF, Sciurba F, Rojas M, Lafyatis R, Shapiro SD, Faner R, Nyunoya T. Single cell RNA sequencing identifies IGFBP5 and QKI as ciliated epithelial cell genes associated with severe COPD. Respir Res. 2021 Apr 6;22(1):100. doi: 10.1186/s12931-021-01675-2. PubMed PMID: 33823868. PubMed Central PMCID: PMC8022543.
33. Crompton D, Gudla S, Waters JH, Sundd P, Kameneva MV. Hemorheological Approach to Improve Perfusion of Red Blood Cells with Reduced Deformability Using Drag-Reducing Polymer (In Vitro Study). ASAIO J. 2021 Aug 16. doi: 10.1097/MAT.0000000000001559. Online ahead of print. PubMed PMID: 34406139.
34. Molina LM, Zhu J, Li Q, Pradhan-Sundd T, Krutsenko Y, Sayed K, Jenkins N, Vats R, Bhushan B, Ko S, Hu S, Poddar M, Singh S, Tao J, Sundd P, Singhi A, Watkins S, Ma X, Benos PV, Feranchak A, Michalopoulos G, Nejak-Bowen K, Watson A, Bell A, Monga SP. Compensatory hepatic adaptation accompanies permanent absence of intrahepatic biliary network due to YAP1 loss in liver progenitors. Cell Rep. 2021 Jul 6;36(1):109310. doi: 10.1016/j.celrep.2021.109310. PubMed PMID: 34233187. 
35. Giordano L, Gregory AD, Pérez Verdaguer M, Ware SA, Harvey H, DeVallance E, Brzoska T, Sundd P, Zhang Y, Sciurba FC, Shapiro SD, Kaufman BA. Extracellular Release of Mitochondrial DNA: Triggered by Cigarette Smoke and Detected in COPD. Cells 2022. Jan 22;11(3):369. doi: 10.3390/cells11030369. PubMed PMID: 35159179. PMCID: PMC8834490.
36. Kaminski TW, Ju EM, Gudapati S, Vats R, Arshad S, Dubey RK, Katoch O, Tutuncuoglu E, Frank J, Brzoska T, Stolz DB, Watkins SC, Chan SY, Ragni MV, Novelli EM, Sundd P, Pradhan-Sundd T. Defenestrated endothelium delays liver-directed gene transfer in hemophilia A mice. Blood Advances. 2022 Jun 28;6(12):3729-3734. doi: 10.1182/bloodadvances.2021006388. PubMed PMID: 35427414.
37. Carreño M, Pires MF, Woodcock SR, Brzoska T, Ghosh S, Salvatore SR, Chang F, Khoo NKH, Dunn M, Connors N, Yuan S, Straub AC, Wendell SG, Kato GJ, Freeman BA, Ofori-Acquah SF, Sundd P, Schopfer FJ, Vitturi DA. Immunomodulatory actions of a kynurenine-derived endogenous electrophile. Science Advances. 2022 Jul;8(26):eabm9138. doi:10.1126/sciadv.abm9138. PubMed PMID: 35767602. PMCID: PMC9242454.
38. Vats R†, Kaminski TW†, Brzoska T, Leech JA, Tutuncuoglu E, Katoch O, Jonassaint JC, Tejero J, Novelli EM, Pradhan-Sundd T, Gladwin MT, Sundd P. Liver to lung microembolic NETs promote Gasdermin-D-dependent inflammatory lung injury in Sickle Cell Disease. Blood. 2022 Sep 1;140(9):1020-1037. doi: 10.1182/blood.2021014552. PubMed PMID: 35737916. This study was the cover article in the Sep 1, 2022 issue of Blood. 

Review Articles:

1. Sundd P*, Pospieszalska MK, Cheung LS, Konstantopoulos K, Ley K. Biomechanics of leukocyte rolling. Biorheology. 2011;48(1):1-35. PubMed PMID: 21515934; PubMed Central PMCID: PMC3103268. A figure from this manuscript was on the cover page of Biorheology. *Corresponding author. 
2. Sundd P, Pospieszalska MK, Ley K. Neutrophil rolling at high shear: flattening, catch bond behavior, tethers and slings. Molecular Immunology. 2013;55(1):59-69. PubMed PMID: 23141302; PubMed Central PMCID: PMC3601566.
3. Sundd P, Ley K. Quantitative dynamic footprinting microscopy. Immunology and cell biology. 2013;91(4):311-320. PubMed PMID: 23478358.
4. Sundd P, Gladwin MT and Novelli EM. Pathophysiology of sickle cell disease. Annu Rev Pathol. 2019 Jan 24;14:263-292. PubMed PMID: 30332562; PubMed Central PMCID: PMC7053558.
5. Fan Z, Mikulski Z, McArdle S, Sundd P, Ley K. Super-STORM: Molecular Modeling to Achieve Single-molecule Localization with STORM Microscopy. STAR Protoc. 2020 Jun 3;1(1):100012. doi: 10.1016/j.xpro.2019.100012. eCollection 2020 Jun 19. PubMed PMID: 33111071.
6. Brzoska T, Kaminski TW, Bennewitz MF, Sundd P. Live Imaging of the Lung. Curr Protoc Cytom. 2020 Dec;95(1):e80. doi: 10.1002/cpcy.80. PubMed PMID: 33226733. PubMed Central PMCID: PMC8021006.
7. Li G, Chen T, Dahlman J, Eniola-Adefeso L, Ghiran IC, Kurre P, Lam WA, Lang JK, Marbán E, Martín P, Momma S, Moos M, Nelson DJ, Raffai RL, Ren X, Sluijter JPG, Stott SL, Vunjak-Novakovic G, Walker ND, Wang Z, Witwer KW, Yang PC, Lundberg MS, Ochocinska MJ, Wong R, Zhou G, Chan SY, Das S, Sundd P. Current challenges and future directions for engineering extracellular vesicles for heart, lung, blood and sleep diseases. J Extracell Vesicles. 2023 Feb;12(2):e12305. doi: 10.1002/jev2.12305.
8. Chiang KC, Gupta A, Sundd P, Krishnamurti L. Thrombo-Inflammation in COVID-19 and Sickle Cell Disease: Two Faces of the Same Coin. Biomedicines 2023 Jan 25;11(2):338. doi: 10.3390/biomedicines11020338. PMID: 36830874 PMCID: PMC9953430. 

Editorials:

1. Sundd P and Kuebler W. Smooth muscle cells: A novel site of P-selectin expression with pathophysiological and therapeutic relevance in pulmonary hypertension. Am J Respir Crit Care Med. 2019 Jun 1;199(11):1307-1309. PubMed PMID: 30592637. PMCID: PMC6543715.

Book Chapters:

1. Tees DFJ, Sundd P, Goetz DJ. A flow chamber for capillary networks: Leukocyte adhesion in capillary-sized, ligand-coated micropipettes. In: Principles of cellular engineering: Understanding the biomolecular interface, edited by M. R. King. New York: Academic Press, 2006.
2. Ley K, Mestas J, Pospieszalska MK, Sundd P, Groisman A, and Zarbock A. Intravital microscopic investigation of leukocyte interactions with the blood vessel wall. In: Methods in Enzymology: Elsevier Academic Press, 445, 2008, p. 255-79. PubMed PMID: 19022063.
3. Sundd, P. & Bennewitz, M.F. Leukocyte kinetics and migration in the lungs. in Hematologic Abnormalities and Acute Lung Syndromes (eds. Lee, J.S. & Donahoe, M.P.) 19-45 (Springer International Publishing, Switzerland, 2017). 10.1007/978-3-319-41912-1. 
4. Brzóska T, Kato GJ and Sundd P. The Role of Platelets in Sickle Cell Disease. In: A. D. Michelson, ed. Platelets. Fourth ed.: Elsevier Inc.; 2019: 563-580. 
5. Sundd P and Ofori-Acquah SF. Sterile inflammation in sickle cell disease. In: Gladwin MT, Kato GJ, Novelli EM, eds. Sickle Cell Disease. New York, NY: McGraw Hill; 2021: 93-108. 

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