Richard Pierce, MD
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Research Summary
My research passion to better understand how blood vessels respond to critical illness. I investigate the translational and basic science of endothelial cell function and dysfunction in culture as well as how these changes affect critically ill. My research starts at the bedside and continues in laboratory. Ultimately, I hope to may a discovery to help reduce blood vessel dysfunction that will help critically ill children.
Extensive Research Description
My three professional passions are providing excellent patient care, educating trainees, and conducting clinically impactful vascular research. In the PICU, I strive to provide compassionate, high quality and timely care to all my patients. Teaching trainees is also a top priority, and I routinely give many formal lectures, short talks as well as create curriculums and educational materials. I invest time and energy in my lectures to make sure they are clinically relevant and are appropriate for all levels of trainees. Finally, I am passionate about my research, where I investigate blood vessel dysfunction and its consequences in critically ill children, with a keen focus on permeability changes. Ultimately, I would like to develop new therapies to target the blood vessels that improve the lives of critically ill children.
My laboratory focuses on several interrelated avenues of research. First, I investigate how EC junctional molecules are regulated in the setting of inflammation. These investigations occur in culture models of capillary endothelium and focus on small GTPases and their regulators, GAPs and GEFs, regulate permeability of EC monolayers and re-organization of tight junction molecules. I demonstrated the importance of the regulation of the small GTPase RhoB in a pediatric patient with systemic capillary leak syndrome caused by a single gene mutation in a GAP with previously unknown function, p190BRhoGAP. We are focused on understanding the GAP and GEF regulation of RhoB have branched to investigate other small GTPases in the Rap family.
A second major avenue of research is on the clinical mechanisms and consequences of EC dysfunction in critically ill children. I place great emphasis on maintaining direct clinical relevance in my research projects and have focused my efforts on human samples. To this end, I established a prospective study investigating the single-cell transcriptomic changes of EC isolated from critically ill children compared to healthy children. This project has identified a new small molecule mediators of blood vessel function in critical illness. This line of research has lead to new investigations into how blood vessels break down and medications that may restore barrier function.
Another focus of my lab is investigating consequences of vascular dyfunction in critically ill children, namely pulmonary capillary dysfunction in pediatric acute lung injury. We leverage cutting edge multi-omic techniques on patient samples to survey immune cells isolated from the lungs of critically ill children with acute lung injury. Finally, I am active in Yale’s own Pediatric Genomic Discovery Program (PGDP) and am able to rapidly investigate the effects of clinically impactful gene mutations on vascular function.
Coauthors
Research Interests
Blood Vessels; Capillary Permeability; Cardiovascular System; Endothelium; Endothelium, Vascular; Pediatrics; Intensive Care Units, Pediatric; Sepsis; Capillary Leak Syndrome; Genomics; Severe Acute Respiratory Syndrome; Acute Lung Injury; Microvessels; Translational Research, Biomedical; COVID-19
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Selected Publications
- Single-cell atlas of the human neonatal small intestine affected by necrotizing enterocolitisEgozi A, Olaloye O, Werner L, Silva T, McCourt B, Pierce R, An X, Wang F, Chen K, Pober J, Shouval D, Itzkovitz S, Konnikova L. Single-cell atlas of the human neonatal small intestine affected by necrotizing enterocolitis PLOS Biology 2023, 21: e3002124. PMID: 37205711, PMCID: PMC10234541, DOI: 10.1371/journal.pbio.3002124.
- A retrospective cohort analysis of the Yale pediatric genomics discovery programAl‐Ali S, Jeffries L, Faustino EVS, Ji W, Mis E, Konstantino M, Zerillo C, Jiang Y, Spencer‐Manzon M, Bale A, Zhang H, McGlynn J, McGrath JM, Tremblay T, Brodsky NN, Lucas CL, Pierce R, Deniz E, Khokha MK, Lakhani SA. A retrospective cohort analysis of the Yale pediatric genomics discovery program American Journal Of Medical Genetics Part A 2022, 188: 2869-2878. PMID: 35899841, PMCID: PMC9474639, DOI: 10.1002/ajmg.a.62918.
- MicroRNA-1 Regulates an Endothelial Gene Network Controlling Permeability and Alveolar Cell DeathKorde A, Haslip M, Chioccioli M, Khan A, Mehta S, Pober J, Pierce R, Takyar S. MicroRNA-1 Regulates an Endothelial Gene Network Controlling Permeability and Alveolar Cell Death 2022, a5771-a5771. DOI: 10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a5771.
- The Integrated Stress Response Is Upregulated in Pulmonary Structural and Immune Cells After Cardiopulmonary Bypass in ChildrenHabet V, Li N, Charkoftaki G, Vasiliou V, Yan X, Dela Cruz C, Pierce R. The Integrated Stress Response Is Upregulated in Pulmonary Structural and Immune Cells After Cardiopulmonary Bypass in Children 2022, a5039-a5039. DOI: 10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a5039.
- ArhGEF12 activates Rap1A and not RhoA in human dermal microvascular endothelial cells to reduce tumor necrosis factor‐induced leakKhan A, Ni W, Baltazar T, Lopez‐Giraldez F, Pober JS, Pierce RW. ArhGEF12 activates Rap1A and not RhoA in human dermal microvascular endothelial cells to reduce tumor necrosis factor‐induced leak The FASEB Journal 2022, 36: e22254. PMID: 35294066, PMCID: PMC9103844, DOI: 10.1096/fj.202101873rr.
- Pediatric Organ Dysfunction Information Update Mandate (PODIUM) Contemporary Organ Dysfunction Criteria: Executive Summary.Bembea MM, Agus M, Akcan-Arikan A, Alexander P, Basu R, Bennett TD, Bohn D, Brandão LR, Brown AM, Carcillo JA, Checchia P, Cholette J, Cheifetz IM, Cornell T, Doctor A, Eckerle M, Erickson S, Farris RWD, Faustino EVS, Fitzgerald JC, Fuhrman DY, Giuliano JS, Guilliams K, Gaies M, Gorga SM, Hall M, Hanson SJ, Hartman M, Hassinger AB, Irving SY, Jeffries H, Jouvet P, Kannan S, Karam O, Khemani RG, Kissoon N, Lacroix J, Laussen P, Leclerc F, Lee JH, Leteurtre S, Lobner K, McKiernan PJ, Menon K, Monagle P, Muszynski JA, Odetola F, Parker R, Pathan N, Pierce RW, Pineda J, Prince JM, Robinson KA, Rowan CM, Ryerson LM, Sanchez-Pinto LN, Schlapbach LJ, Selewski DT, Shekerdemian LS, Simon D, Smith LS, Squires JE, Squires RH, Sutherland SM, Ouellette Y, Spaeder MC, Srinivasan V, Steiner ME, Tasker RC, Thiagarajan R, Thomas N, Tissieres P, Traube C, Tucci M, Typpo KV, Wainwright MS, Ward SL, Watson RS, Weiss S, Whitney J, Willson D, Wynn JL, Yehya N, Zimmerman JJ. Pediatric Organ Dysfunction Information Update Mandate (PODIUM) Contemporary Organ Dysfunction Criteria: Executive Summary. Pediatrics 2022, 149: s1-s12. PMID: 34970673, PMCID: PMC9599725, DOI: 10.1542/peds.2021-052888b.
- Endothelial Dysfunction Criteria in Critically Ill Children: The PODIUM Consensus Conference.Pierce RW, Giuliano JS, Whitney JE, Ouellette Y. Endothelial Dysfunction Criteria in Critically Ill Children: The PODIUM Consensus Conference. Pediatrics 2022, 149: s97-s102. PMID: 34970676, PMCID: PMC9754809, DOI: 10.1542/peds.2021-052888o.
- Integrated Single Cell Atlas of Endothelial Cells of the Human LungSchupp JC, Adams TS, Cosme C, Raredon MSB, Yuan Y, Omote N, Poli S, Chioccioli M, Rose KA, Manning EP, Sauler M, DeIuliis G, Ahangari F, Neumark N, Habermann AC, Gutierrez AJ, Bui LT, Lafyatis R, Pierce RW, Meyer KB, Nawijn MC, Teichmann SA, Banovich NE, Kropski JA, Niklason LE, Pe’er D, Yan X, Homer RJ, Rosas IO, Kaminski N. Integrated Single Cell Atlas of Endothelial Cells of the Human Lung Circulation 2021, 144: 286-302. PMID: 34030460, PMCID: PMC8300155, DOI: 10.1161/circulationaha.120.052318.
- Tumor necrosis factor‐induced ArhGEF10 selectively activates RhoB contributing to human microvascular endothelial cell tight junction disruptionKhan A, Ni W, Lopez‐Giraldez F, Kluger MS, Pober JS, Pierce RW. Tumor necrosis factor‐induced ArhGEF10 selectively activates RhoB contributing to human microvascular endothelial cell tight junction disruption The FASEB Journal 2021, 35: e21627. PMID: 33948992, PMCID: PMC9026622, DOI: 10.1096/fj.202002783rr.
- Pazopanib ameliorates acute lung injuries via inhibition of MAP3K2 and MAP3K3Yuan Q, Basit A, Liang W, Qu R, Luan Y, Ren C, Li A, Xu X, Liu X, Yang C, Kuo A, Pierce R, Zhang L, Turk B, Hu X, Li F, Cui W, Li R, Huang D, Mo L, Sessa WC, Lee PJ, Kluger Y, Su B, Tang W, He J, Wu D. Pazopanib ameliorates acute lung injuries via inhibition of MAP3K2 and MAP3K3 Science Translational Medicine 2021, 13 PMID: 33910977, PMCID: PMC8466683, DOI: 10.1126/scitranslmed.abc2499.
- Immune dysregulation and autoreactivity correlate with disease severity in SARS-CoV-2-associated multisystem inflammatory syndrome in childrenRamaswamy A, Brodsky NN, Sumida TS, Comi M, Asashima H, Hoehn KB, Li N, Liu Y, Shah A, Ravindra NG, Bishai J, Khan A, Lau W, Sellers B, Bansal N, Guerrerio P, Unterman A, Habet V, Rice AJ, Catanzaro J, Chandnani H, Lopez M, Kaminski N, Dela Cruz CS, Tsang JS, Wang Z, Yan X, Kleinstein SH, van Dijk D, Pierce RW, Hafler DA, Lucas CL. Immune dysregulation and autoreactivity correlate with disease severity in SARS-CoV-2-associated multisystem inflammatory syndrome in children Immunity 2021, 54: 1083-1095.e7. PMID: 33891889, PMCID: PMC8043654, DOI: 10.1016/j.immuni.2021.04.003.
- Post-infectious inflammatory disease in MIS-C features elevated cytotoxicity signatures and autoreactivity that correlates with severity.Ramaswamy A, Brodsky NN, Sumida TS, Comi M, Asashima H, Hoehn KB, Li N, Liu Y, Shah A, Ravindra NG, Bishai J, Khan A, Lau W, Sellers B, Bansal N, Guerrerio P, Unterman A, Habet V, Rice AJ, Catanzaro J, Chandnani H, Lopez M, Kaminski N, Dela Cruz CS, Tsang JS, Wang Z, Yan X, Kleinstein SH, van Dijk D, Pierce RW, Hafler DA, Lucas CL. Post-infectious inflammatory disease in MIS-C features elevated cytotoxicity signatures and autoreactivity that correlates with severity. MedRxiv : The Preprint Server For Health Sciences 2021 PMID: 33300011, PMCID: PMC7724682, DOI: 10.1101/2020.12.01.20241364.
- Single-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium identifies target cells, alterations in gene expression, and cell state changesRavindra NG, Alfajaro MM, Gasque V, Huston NC, Wan H, Szigeti-Buck K, Yasumoto Y, Greaney AM, Habet V, Chow RD, Chen JS, Wei J, Filler RB, Wang B, Wang G, Niklason LE, Montgomery RR, Eisenbarth SC, Chen S, Williams A, Iwasaki A, Horvath TL, Foxman EF, Pierce RW, Pyle AM, van Dijk D, Wilen CB. Single-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium identifies target cells, alterations in gene expression, and cell state changes PLOS Biology 2021, 19: e3001143. PMID: 33730024, PMCID: PMC8007021, DOI: 10.1371/journal.pbio.3001143.
- Single-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium.Ravindra NG, Alfajaro MM, Gasque V, Habet V, Wei J, Filler RB, Huston NC, Wan H, Szigeti-Buck K, Wang B, Wang G, Montgomery RR, Eisenbarth SC, Williams A, Pyle AM, Iwasaki A, Horvath TL, Foxman EF, Pierce RW, van Dijk D, Wilen CB. Single-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium. BioRxiv : The Preprint Server For Biology 2020 PMID: 32511382, PMCID: PMC7263511, DOI: 10.1101/2020.05.06.081695.
- BMX Represses Thrombin-PAR1–Mediated Endothelial Permeability and Vascular Leakage During Early SepsisLi Z, Yin M, Zhang H, Ni W, Pierce R, Zhou HJ, Min W. BMX Represses Thrombin-PAR1–Mediated Endothelial Permeability and Vascular Leakage During Early Sepsis Circulation Research 2020, 126: 471-485. PMID: 31910739, PMCID: PMC7035171, DOI: 10.1161/circresaha.119.315769.
- Sera From Children After Cardiopulmonary Bypass Reduces Permeability of Capillary Endothelial Cell BarriersPierce RW, Zahr RA, Kandil S, Faustino EVS, Pober JS. Sera From Children After Cardiopulmonary Bypass Reduces Permeability of Capillary Endothelial Cell Barriers Pediatric Critical Care Medicine 2018, 19: 609-618. PMID: 29652749, PMCID: PMC6037548, DOI: 10.1097/pcc.0000000000001553.
- Complete Recovery After Acute Zonisamide Overdose in an Adolescent FemaleMcStay C, Pierce R, Riley C. Complete Recovery After Acute Zonisamide Overdose in an Adolescent Female Pediatric Emergency Care 2018, 34: e30-e31. PMID: 27749631, DOI: 10.1097/pec.0000000000000854.
- A p190BRhoGAP mutation and prolonged RhoB activation in fatal systemic capillary leak syndromePierce RW, Merola J, Lavik JP, Kluger MS, Huttner A, Khokha MK, Pober JS. A p190BRhoGAP mutation and prolonged RhoB activation in fatal systemic capillary leak syndrome Journal Of Experimental Medicine 2017, 214: 3497-3505. PMID: 29097442, PMCID: PMC5716031, DOI: 10.1084/jem.20162143.
- A Case of Succinyl-CoA:3-Oxoacid CoA Transferase Deficiency Presenting with Severe Acidosis in a 14-Month-Old Female: Evidence for Pathogenicity of a Point Mutation in the OXCT1 GeneZheng DJ, Hooper M, Spencer-Manzon M, Pierce RW. A Case of Succinyl-CoA:3-Oxoacid CoA Transferase Deficiency Presenting with Severe Acidosis in a 14-Month-Old Female: Evidence for Pathogenicity of a Point Mutation in the OXCT1 Gene Journal Of Pediatric Intensive Care 2017, 07: 062-066. PMID: 31073471, PMCID: PMC6260335, DOI: 10.1055/s-0037-1604270.
- Endothelial Cell Function and Dysfunction in Critically Ill ChildrenPierce RW, Giuliano JS, Pober JS. Endothelial Cell Function and Dysfunction in Critically Ill Children Pediatrics 2017, 140: e20170355. PMID: 28759412, PMCID: PMC9923607, DOI: 10.1542/peds.2017-0355.
- A Survey of Pediatric Critical Care Providers on the Presence, Severity, and Assessment of Capillary Leak in Critically Ill ChildrenPierce R, Luckett PM, Faustino EVS. A Survey of Pediatric Critical Care Providers on the Presence, Severity, and Assessment of Capillary Leak in Critically Ill Children Journal Of Pediatric Intensive Care 2016, 06: 145-151. PMID: 31073440, PMCID: PMC6260295, DOI: 10.1055/s-0036-1593388.
- IL-17 Promotes Neutrophil-Mediated Immunity by Activating Microvascular Pericytes and Not EndotheliumLiu R, Lauridsen HM, Amezquita RA, Pierce RW, Jane-Wit D, Fang C, Pellowe AS, Kirkiles-Smith NC, Gonzalez AL, Pober JS. IL-17 Promotes Neutrophil-Mediated Immunity by Activating Microvascular Pericytes and Not Endothelium The Journal Of Immunology 2016, 197: 2400-2408. PMID: 27534549, PMCID: PMC5010945, DOI: 10.4049/jimmunol.1600138.
- Association of thrombophilia and catheter‐associated thrombosis in children: a systematic review and meta‐analysisNeshat‐Vahid S, Pierce R, Hersey D, Raffini LJ, Faustino EV. Association of thrombophilia and catheter‐associated thrombosis in children: a systematic review and meta‐analysis Journal Of Thrombosis And Haemostasis 2016, 14: 1749-1758. PMID: 27306795, PMCID: PMC5035642, DOI: 10.1111/jth.13388.
- 97Pierce R, Khokha M, Kluger M, Lavik J, Pober J. 97 Critical Care Medicine 2015, 43: 25-26. DOI: 10.1097/01.ccm.0000473925.14912.a3.
- Use of procalcitonin for the prediction and treatment of acute bacterial infection in childrenPierce R, Bigham MT, Giuliano JS. Use of procalcitonin for the prediction and treatment of acute bacterial infection in children Current Opinion In Pediatrics 2014, 26: 292-298. PMID: 24739491, DOI: 10.1097/mop.0000000000000092.
- Evolution of Enzymatic Activities in the Enolase Superfamily: l-Fuconate Dehydratase from Xanthomonas campestris † , ‡Yew WS, Fedorov AA, Fedorov EV, Rakus JF, Pierce RW, Almo SC, Gerlt JA. Evolution of Enzymatic Activities in the Enolase Superfamily: l-Fuconate Dehydratase from Xanthomonas campestris † , ‡ Biochemistry 2006, 45: 14582-14597. PMID: 17144652, DOI: 10.1021/bi061687o.
- Rotational analysis of bands in the high-resolution infrared spectra of the three species of butadiene-1,4-d 2; refinement of the assignments of the vibrational fundamentalsCraig N, Hanson K, Pierce R, Saylor S, Sams R. Rotational analysis of bands in the high-resolution infrared spectra of the three species of butadiene-1,4-d 2; refinement of the assignments of the vibrational fundamentals Journal Of Molecular Spectroscopy 2004, 228: 401-413. DOI: 10.1016/j.jms.2004.07.001.
Clinical Trials
Conditions | Study Title |
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Children's Health; Genetics - Pediatric | Pediatric Genomics Discovery Program (PGDP) |