Krithika Lingappan, MD, PhD, MS

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Krithika Lingappan, MD, PhD, MS, is an attending neonatologist with the Division of Neonatology at Children's Hospital of Philadelphia.

Locations: Main Hospital
Appointments and Referrals: 1-800-TRY-CHOP (1-800-879-2467)

Background

Krithika Lingappan, MD, PhD, MS's, unique niche is to elucidate the mechanisms sex-specific differences in neonatal hyperoxic lung injury with the goal to develop individualized therapeutic options to decrease morbidity in preterm babies. Sex-specific differences exist in various forms of organ injury in adults and children. Acute respiratory distress syndrome (ARDS) is a devastating clinical disorder and mortality in ARDS was higher in males compared to females. Neonatal outcomes for males are worse than females for many diseases, including bronchopulmonary dysplasia (BPD). NIH policy statement underlines the importance of sex-specific research in preclinical animal and in vitro studies. Being a neonatologist, Dr. Lingappan's interest was in the field of neonatal lung injury and repair. The incidence of BPD is higher among premature male neonates even after adjusting for other confounders. Despite the well-established sex-specific differences in the incidence of BPD and impaired lung function in males, the molecular mechanism(s) behind this remain unknown. Her research focuses on sex-specific differences in neonatal hyperoxic lung injury.

Education and Training

Medical School

MBBS - Kilpauk Medical College, Chennai, India

Residency

Pediatrics - Post Graduate Institute of Medical Education and Research, Chandigarh, India
Pediatrics - Miami Children's Hospital, Miami, FL
Pediatrics - University of Chicago, Chicago, IL

Fellowship

Neonatal-Perinatal Medicine - Baylor College of Medicine, Houston, TX

Board Certification

Neonatal-Perinatal Medicine
Pediatrics

Graduate Degree

MS, Clinical Scientist Training Program - Baylor College of Medicine, Houston, TX
PhD, Clinical Scientist Training Program - Baylor College of Medicine, Houston, TX

Titles and Academic Titles

Attending Physician

Associate Professor of Pediatrics, Perelman School of Medicine at the University of Pennsylvania

Departments and Services

Publications

Papers

2021

Jain PN, Robertson M, Lasa JJ, Shekerdemian L, Guffey D, Zhang Y, Lingappan K, Checchia P, Coarfa C: Altered metabolic and inflammatory transcriptomics after cardiac surgery in neonates with congenital heart disease. Sci Rep.  2021.

2020

Lingappan K, Savani RC.: The Wnt Signaling Pathway and the Development of Bronchopulmonary Dysplasia. Am J Respir Crit Care Med 201: 1174-1176, May 2020.

Al-Mudares F, Reddick S, Ren J, Venkatesh A, Zhao C,  Lingappan K: Role of Growth Differentiation Factor 15 in Lung Disease and Senescence: Potential Role Across the Lifespan. Frontiers in Medicine. Frontiers in Medicine 2020.

Callaway DA, Jiang W, Wang L, Lingappan K, Moorthy B: Oxygen-mediated lung injury in mice lacking the gene for NRF2: Rescue with the cytochrome P4501A-inducer, beta-naphthoflavone (BNF), and differential sex-specific effects. Free Radic Biol Med 2020.

Coarfa C, Grimm SL, Katz T, Zhang Y, Jangid RK, Walker CL, Moorthy B, Lingappan K: Epigenetic response to hyperoxia in the neonatal lung is sexually dimorphic. Redox Biol 2020.

Lingappan K, Karmouty-Quintana H, Davies J, Akkanti B, Harting MT: Understanding the age-divide in COVID-19: why are children overwhelmingly spared?  Am J Physiol Lung Cell Mol Physiol 2020.

Lingappan K, Savani R: The Wnt Signaling pathway and the development of Bronchopulmonary Dysplasia. Am J Respir Crit Care Med 2020.

Stading R, Chu C, Couroucli X, Lingappan K, Moorthy B: Molecular role of cytochrome P4501A enzymes in oxidative stress. Curr Opin Toxicol 2020.

Stading R, Couroucli X, Lingappan K, Moorthy B: The role of cytochrome P450 (CYP) enzymes in hyperoxic lung injury. Expert Opin Drug Metab Toxicol 2020.

2019

Zhang Y, Coarfa C, Dong X, Jiang W, Hayward-Piatkovskyi B, Gleghorn JP, Lingappan K.: MicroRNA-30a as a candidate underlying sex-specific differences in neonatal hyperoxic lung injury: implications for BPD. Am J Physiol Lung Cell Mol Physiol 316: L144-L156, Jan 2019.

Suter MA, Aagaard KM, Coarfa C, Robertson M, Zhou G, Jackson BP, Thompson D, Putluri V, Putluri N, Hagan J, Wang L, Jiang W, Lingappan K, Moorthy B.: Association between elevated placental polycyclic aromatic hydrocarbons (PAHs) and PAH-DNA adducts from Superfund sites in Harris County, and increased risk of preterm birth (PTB). Biochem Biophys Res Commun 516: 344-349, Aug 2019.

Althouse MH, Stewart C, Jiang W, Moorthy B, Lingappan K.: Impact of Early Life Antibiotic Exposure and Neonatal Hyperoxia on the Murine Microbiome and Lung Injury. Sci Rep 9: 14992, Oct 2019.

Zhang Y, Dong X, Lingappan K.: Role of HIF-1α-miR30a-Snai1 Axis in Neonatal Hyperoxic Lung Injury. Oxid Med Cell Longev 2019: 8327486, Oct 2019.

2018

Jiang W, Maturu P, Liang YW, Wang L, Lingappan K, Couroucli X.: Hyperoxia-mediated transcriptional activation of cytochrome P4501A1 (CYP1A1) and decreased susceptibility to oxygen-mediated lung injury in newborn mice. Biochem Biophys Res Commun 495: 408-413, Jan 2018.

Lingappan K, Maturu P, Liang YW, Jiang W, Wang L, Moorthy B, Couroucli XI.: β-Naphthoflavone treatment attenuates neonatal hyperoxic lung injury in wild type and Cyp1a2-knockout mice. Toxicol Appl Pharmacol 339: 133-142, Jan 2018.

Lingappan K.: NF-κB in Oxidative Stress. Curr Opin Toxicol 7: 81-86, Feb 2018.

Thomas AN, Hagan JL, Lingappan K.: Noninvasive ventilation strategies: which to choose? J Perinatol 38: 447-450, May 2018.

Lingappan K, Arnold JL, Fernandes CJ, Pammi M.: Videolaryngoscopy versus direct laryngoscopy for tracheal intubation in neonates. Cochrane Database Syst Rev 6: CD009975, Jun 2018.

Veith AC, Bou Aram B, Jiang W, Wang L, Zhou G, Jefcoate CR, Couroucli XI, Lingappan K, Moorthy B.: Mice Lacking the Cytochrome P450 1B1 Gene Are Less Susceptible to Hyperoxic Lung Injury Than Wild Type. Toxicol Sci 165: 462-474, Oct 2018.

Balaji S, Dong X, Li H, Zhang Y, Steen E, Lingappan K.: Sex-specific differences in primary neonatal murine lung fibroblasts exposed to hyperoxia in vitro: implications for bronchopulmonary dysplasia. Physiol Genomics 50: 940-946, Nov 2018.

Zhang Y, Dong X, Shirazi J, Gleghorn JP, Lingappan K.: Pulmonary endothelial cells exhibit sexual dimorphism in their response to hyperoxia. Am J Physiol Heart Circ Physiol 315: H1287-H1292, Nov 2018.

2017

Hoover J, Lingappan K.: One-Month-Old Infant With Hypotonia and Cardiorespiratory Arrest. Clin Pediatr (Phila) 56: 397-398, Apr 2017.

Zhang Y, Lingappan K.: Differential sex-specific effects of oxygen toxicity in human umbilical vein endothelial cells. Biochem Biophys Res Commun 486: 431-437, Apr 2017.

Maturu P, Wei-Liang Y, Jiang W, Wang L, Lingappan K, Barrios R, Liang Y, Moorthy B, Couroucli XI.: Newborn Mice Lacking the Gene for Cyp1a1 Are More Susceptible to Oxygen-Mediated Lung Injury, and Are Rescued by Postnatal β-Naphthoflavone Administration: Implications for Bronchopulmonary Dysplasia in Premature Infants. Toxicol Sci 157: 260-271, May 2017.

Parmekar S, Arnold JL, Anselmo C, Pammi M, Hagan J, Fernandes CJ, Lingappan K.: Mind the gap: can videolaryngoscopy bridge the competency gap in neonatal endotracheal intubation among pediatric trainees? a randomized controlled study. J Perinatol 37: 979-983, Aug 2017.

Zhang Y, Jiang W, Wang L, Lingappan K.: Sex-specific differences in the modulation of Growth Differentiation Factor 15 (GDF15) by hyperoxia in vivo and in vitro: Role of Hif-1α Toxicol Appl Pharmacol 332: 8-14, Oct 2017.

Coarfa C, Zhang Y, Maity S, Perera DN, Jiang W, Wang L, Couroucli X, Moorthy B, Lingappan K.: Sexual dimorphism of the pulmonary transcriptome in neonatal hyperoxic lung injury: identification of angiogenesis as a key pathway. Am J Physiol Lung Cell Mol Physiol 313: L991-L1005, Dec 2017.

Maity S, Jiang W, Wang L, Couroucli X, Veith A, Zhou G, Coarfa C, Moorthy B: Role of Cytochrome P450 (CYP)1A in Hyperoxic Lung Injury: Analysis of the Transcriptome and Proteome  Sci Rep. 2017.

Pammi M, Lingappan K, Carbajal MM, Suresh GK.: Focused Evidence-Based Medicine Curriculum for Trainees in Neonatal-Perinatal Medicine. MedEdPORTAL 13: 10664, Dec 2017.

2016

Dinu D, Chu C, Veith A, Lingappan K, Couroucli X, Jefcoate CR, Sheibani N, Moorthy B.: Mechanistic role of cytochrome P450 (CYP)1B1 in oxygen-mediated toxicity in pulmonary cells: A novel target for prevention of hyperoxic lung injury. Biochem Biophys Res Commun 476: 346-351, Aug 2016.

Lingappan K, Jiang W, Wang L, Moorthy B.: Sex-specific differences in neonatal hyperoxic lung injury. Am J Physiol Lung Cell Mol Physiol 311: L481-93, Aug 2016.

Lingappan K, Kaiser JR, Srinivasan C, Gunn AJ.: Relationship between PCO2 and unfavorable outcome in infants with moderate-to-severe hypoxic ischemic encephalopathy. Pediatr Res 80: 204-8, Aug 2016.

2015

Lingappan K, Jiang W, Wang L, Couroucli XI, Moorthy B.: Sex-specific differences in hyperoxic lung injury in mice: role of cytochrome P450 (CYP)1A. Toxicology 331: 14-23, May 2015.

Wang L, Lingappan K, Jiang W, Couroucli XI, Welty SE, Shivanna B, Barrios R, Wang G, Firoze Khan M, Gonzalez FJ, Jackson Roberts L, Moorthy B.: Disruption of cytochrome P4501A2 in mice leads to increased susceptibility to hyperoxic lung injury. Free Radic Biol Med 82: 147-59, May 2015.

Tiwari KK, Moorthy B, Lingappan K.: Role of GDF15 (growth and differentiation factor 15) in pulmonary oxygen toxicity. Toxicol In Vitro 29: 1369-76, Oct 2015.

Lingappan K, Moorthy B.: Can maternal DHA supplementation offer long-term protection against neonatal hyperoxic lung injury? Am J Physiol Lung Cell Mol Physiol 309: L1383-6, Dec 2015.

2014

Lingappan K, Srinivasan C, Jiang W, Wang L, Couroucli XI, Moorthy B.: Analysis of the transcriptome in hyperoxic lung injury and sex-specific alterations in gene expression. PLoS One 9: e101581, Jul 2014.

Tiwari KK, Chu C, Couroucli X, Moorthy B, Lingappan K.: Differential concentration-specific effects of caffeine on cell viability, oxidative stress, and cell cycle in pulmonary oxygen toxicity in vitro. Biochem Biophys Res Commun 450: 1345-50, Aug 2014.

Lingappan K, Jiang W, Wang L, Wang G, Couroucli XI, Shivanna B, Welty SE, Barrios R, Khan MF, Nebert DW, Roberts LJ, Moorthy B.: Mice deficient in the gene for cytochrome P450 (CYP)1A1 are more susceptible than wild-type to hyperoxic lung injury: evidence for protective role of CYP1A1 against oxidative stress. Toxicol Sci 141: 68-77, Sep 2014.

Thakur VS, Liang YW, Lingappan K, Jiang W, Wang L, Barrios R, Zhou G, Guntupalli B, Shivanna B, Maturu P, Welty SE, Moorthy B, Couroucli XI.: Increased susceptibility to hyperoxic lung injury and alveolar simplification in newborn rats by prenatal administration of benzo[a]pyrene. Toxicol Lett 230: 322-32, Oct 2014.

2013

Lingappan K, Arunachalam A, Pammi M.: Lactoferrin and the newborn: current perspectives. Expert Rev Anti Infect Ther 11: 695-707, Jul 2013.

Lingappan K, Jiang W, Wang L, Couroucli XI, Barrios R, Moorthy B.: Sex-specific differences in hyperoxic lung injury in mice: implications for acute and chronic lung disease in humans. Toxicol Appl Pharmacol 272: 281-90, Oct 2013.

2006

Singh M, Lingappan K.: Whooping cough: the current scene. Chest 130: 1547-53, Nov 2006.

Books

2020

Lingappan K, Hayward-Piatkovskyi B, Gleghorn JP: Neonatal Lung Diseases: mechanisms driving sex differences. Sex-Based Differences in Lung Physiology. Silveyra, Patricia, Tigno, Xenia (eds.). Springer International Publishing, 2020.

Lingappan K, Hayward-Piatkovskyi B, Gleghorn JP: Neonatal Lung Diseases: mechanisms driving sex differences. Sex-Based Differences in Lung Physiology. American Physiological Society and Springer-Nature (eds.). American Physiological Society and Springer-Nature, 2020.

Chapters
2016

Lingappan K, Suresh GK: Assisted Ventilation of the Neonate: An Evidence-Based Approach to Newborn Respiratory Care. Chapter 5: Evidence based respiratory care  Assisted Ventilation of the Neonate. Elsevier Health Sciences. Page: 41-48, 2016.

Posters and Presentations

2019

Althouse M, Venkatachalam A, Thapa S, Ford S, Lingappan K, Hagan J, Luna RA, Hair A: Preterm Infants With Severe Bronchopulmonary Dysplasia Develop A Less Diverse Intestinal Microbiome. Poster Presentation, Pediatric Academic Societies Meeting, Baltimore, MD 2019.

Callaway D, Jiang W, Lingappan K, Moorthy B: Decreased Survival and Increased Oxygen-Mediated Lung Injury in Mice Lacking Nrf2: Protection by Beta-Naphthoflavone. Poster Presentation, American Thoracic Societies Meeting, Dallas TX 2019.

Callaway D, Weiwu J, Lingappan K, Moorthy B.: Sex impacts survival and oxygen-mediated lung injury in mice lacking Nrf2: Rescue and abrogation of sex differences with beta-naphthoflavone. Platform Presentation, Pediatric Academic Societies Meeting, Baltimore, MD 2019.

Coarfa C, Veith AC, Robertson MJ, Lingappan K, Moorthy B: Analysis of Hyperoxic Lung Injury in Mice Deficient in Gene for Cytochrome P450 (CYP)1b1, 1a1 or 1a2. Poster Presentation, American Thoracic Societies Meeting, Dallas, TX 2019.

Couroucli X, Liang YW, Lingappan K, Maturu P, Jiang W, Moorthy B: Oral Maternal Administration of the Cytochrome P450 (CYP)1A/1B Inducer, Beta-Napthoflavone (BNF), Attenuates Oxygen-Mediated Lung Injury in Newborn Mice: Implications for Bronchopulmonary Dysplasia (BPD). Poster Presentation, American Thoracic Societies Meeting, Dallas, TX 2019.

Hayward B, Shirazi J, Lingappan K, Gleghorn, J: The role of hormones on sex-based differences related to pulmonary vascular development and their implications in bronchopulmonary dysplasia. Poster Presentation, Pediatric Academic Societies Meeting, Baltimore, MD 2019.

Lingappan K, Dong X, Zhang Y: Sex-Specific miR-30a Mediated Snai1 Inhibition Decreases Pathologic Fibrosis in BPD. Poster Presentation, American Thoracic Societies Meeting, Dallas, TX 2019.

Lingappan K, Katz T, Kumar R, Walker C, Moorthy B, Coarfa C: Integrative Epigenomic/Transcriptomic Analysis of Sex-Biased Differences in in a Murine Model of Neonatal Hyperoxic Lung Injury. Poster Presentation, American Thoracic Societies Meeting, Dallas, TX.  2019.

Lingappan K, Veith A, Jiang W, Maturu P, Couroucli X I, Moorthy : Maternal Exposure of Mice to Benzo[a]pyrene (BP) Leads to Potentiation of Neonatal Hyperoxic Lung Injury and Dysbiosis of Intestinal Microbiome: Potential Role of Gut-Lung Axis. Poster Presentation, American Thoracic Societies Meeting, Dallas, TX 2019.

Moorthy B, Lingappan K, Couroucli XI, Weiwu J: Novel role of the endogenous Ah receptor (AHR) ligand 6-formyllindolo[3,2- b]carbazole (FICZ) in cytochtrome P450 (CYP)1A induction and in the protection against hyperoxic lung injury. Poster Presentation, Pediatric Academic Societies Meeting, Baltimore, MD 2019.

Zhang Y, Dong X, Lingappan K: Injury: Implications for Bronchopulmonary Dysplasia. Poster Presentation, Pediatric Academic Societies Meeting, Baltimore, MD 2019.

Invited Lectures

2020

Lingappan K. "Why is sex crucial in determining outcomes in the NICU? An insight into the mechanisms", University of Wisconsin, Division of Neonatology Research Seminar, Madison, WI. Dec 2020.

Lingappan K. "Sex as a Biological Variable in Neonatal Hyperoxic Lung Injury", Children's Hospital of Philadelphia, Section of Neonatology Research Seminar, Philadelphia, PA. Oct 2020.

Lingappan K. "Evidence-Based management of preterm PDA: relevance of Cath-based options", Grand Rounds at Women's Hospital of Texas, Houston, TX. July 2020.

Lingappan K. "Appraising evidence and having fun doing it", Organization of Neonatal-Perinatal Medicine Training Program Directors, Online with Experts Virtual Lecture. June 2020.

Lingappan K. "So you think you can breathe; a primer on lung development and control of breathing, Organization of Neonatal-Perinatal Medicine Training Program Directors, Online with Experts Virtual Lecture. May 2020.

Lingappan K. "Sex as a biological variable in neonatal hyperoxic lung injury", Experimental Biology Meeting, San Diego, CA. Apr 2020.

Lingappan K. "Lung Development, Surfactant Biology and Neonatal Pulmonology pot-pourri ", The 2020 NeoPREP meeting, Long Beach, CA. Feb 2020.

Lingappan K. "Mallinckrodt Neonatology-Pulmonary State-of-the-Art", Western Society of Pediatric Research (WSPR) meeting, Carmel, CA. Jan 2020.

Lingappan K. "Sex as a Crucial Biological Variable in Neonatal Hyperoxic Lung Injury:  Implications for Bronchopulmonary Dysplasia", Texas Children's Feigin Center Research Seminar, Houston, TX. Jan 2020.

2019

Lingappan K. "NIH Mock Grant Review", Feigin Center Research Symposium at Texas Children's Hospital, Houston, TX. Oct 2019.

Lingappan K. "What's new on the Neonatal respiratory Front?", Baylor Avoiding Lung Injury Symposium held at Baylor College of Medicine, Houston, TX. Oct 2019.

Lingappan K. "What's new on the Neonatal respiratory Front?", Baylor Avoiding Lung Injury Symposium, Baylor College of Medicine, Houston, TX. Oct 2019.

Lingappan K. "Molecular mechanisms behind sex-specific differences in Bronchopulmonary Dysplasia", Perinatal Research Center Grand Rounds, Nationwide Children's Hospital, Columbus, OH. Oct 2019.

Lingappan K. "Sex as a Crucial Biological Variable in Neonatal Lung Injury and Repair", the Lung Gordon Conference, Lung development, Injury and Repair, Bates College, Lewistown, ME. Aug 2019.

Lingappan K. "Postgraduate Course: Optimizing Management of the Patient with Severe Bronchopulmonary Dysplasia. What's new in the management of severe BPD?", American Thoracic Societies Annual International meeting, Dallas, TX. May 2019.

Lingappan K. "Sex as a biological variable in BPD", Pediatric Grand Rounds, The Pediatric Research Series, Department of Pediatrics, Penn State Health Children's Hospital, Hershey, PA. Jan 2019.

Lingappan K. "Sex as a Vital Biological Variable in Neonatal Hyperoxic Lung Injury", Research Conference, Section of Neonatology, Medical University of South Carolina, Charleston, SC. Jan 2019.

Awards and Honors

2019, Women of Excellence Award, Baylor College of Medicine
2019, Young Investigator Award, Baylor College of Medicine, Department of Pediatrics
2019, Norton Rose Fulbright Faculty Excellence Award for Teaching and Evaluation, Baylor College of Medicine
2016, Best Research Award, Third Annual Neonatal Cardiopulmonary Biology Young Investigators' Forum
2015-2017, Southern Society of Pediatric Research Faculty Award for Research
2012, The Arnold J. Rudolph Award for outstanding teaching, patient care, scientific inquiry and professional integrity, Baylor College of medicine Department of Pediatrics Section of Neonatology
2011, First Place in the Texas Pediatric Society Fellow and resident Poster Contest under the Hypothesis driven research Section
2011, Young Investigator Award for oral presentation, Perinatal Section of the American Academy of Pediatrics
2010, Second place in poster presentation." Injury due to hyperoxia: Differences between the sexes.", Gulf Coast Society of Toxicology Meeting, Houston, TX
2005, Silver medal for performance in final examination, Post Graduate Institute of Medical Education and Research, Chandigarh, India
2002, Horlicks Cash Award in recognition of performance in Bachelor of Medicine and Surgery Examination, Kilpauk Medical College, India
2002, Award for highest score in Clinical Exam in Obstetrics and Gynecology, Kilpauk Medical College, India
2002, The Balfour Memorial Medals for performance in Internal medicine, Kilpauk Medical College, India
2002, Gold Medal in Microbiology, Kilpauk Medical College, India
2000, Gold Medal in Pediatrics, Kilpauk Medical College, India
2000, Gold Medal in Internal Medicine Kilpauk Medical College, India
1999, Gold Medal in Pathology, Kilpauk Medical College, India
1999, Gold Medal in Ophthalmology, Kilpauk Medical College, India
1999, Gold Medal in Otolaryngology, Kilpauk Medical College, India
1997, Gold Medal in Anatomy, Kilpauk Medical College, India

Editorial and Academic Positions

Editorial Positions

2019-present, Journal Reviewer, Redox Biology
2019-present, Editorial Board, AJP Lung Molecular and Cellular Physiology
2019, Journal Reviewer, Lancet
2019-present, Editorial Board, NeoReviews
2019, Journal Reviewer, Scientific Reports: American Journal of Respiratory and Critical Care Medicine
2017-present, Editorial Board, Anatomical Record
2016-present, Journal Reviewer, Journal of Perinatology
2015-present, Journal Reviewer, Pediatric Research
2015-present, Journal Reviewer, AJP-Lung and Molecular Physiology

Leadership and Memberships

Memberships in Professional Organizations

2017, Perinatal Research Society
2016, Pediatric Academic Societies
2016-present, Society of Toxicology
2015-present, American Thoracic Society
 - 2019-present, Respiratory Cell and Molecular Biology Program Committee
2010-present, American Academy of Pediatrics
 - 2021-present, Section of Neonatal-Perinatal Medicine Marshall Klaus Awards Grant Review
 - 2020-present, Section of Neonatal-Perinatal Medicine Website Committee, Chair
 - 2019-present, Section of Neonatal-Perinatal Medicine Quality Measures Task Force