Sarangarajan Ranganathan, MD
Professor of Pathology
Dr. Ranganathan is the Director of Anatomic Pathology, Division of Pediatric Pathology, Children's Hospital of Pittsburgh. He oversees the running of the AP lab at CHP and helps maintain quality in the Division. As a senior member of the Clinical Team he oversees the training of junior faculty and also helps in diagnosis of difficult pediatric lesions/diseases encountered in the division. He has served as faculty mentors for Pediatric Hematology Oncology and Pediatric Gastroenterology fellows. He is the Institutional Pathologist for Children's Oncology Group (COG) studies and a consultant for pediatric liver tumors as part of the COG.
B260, Main Hospital
Department of Pathology
Children's Hospital of UPMC
4401 Penn Avenue
Pittsburgh PA 15224
Office Telephone: 412-692-5650
- MBBS - 1985, Topiwala National Medical College, Mumbai
- MD - 1990, Topiwala National Medical College, Mumbai
- Pediatric Tumors: I have been involved in Children's Oncology group for several years and have been part of the Ewings sarcoma study as well as current hepatoblastoma reviewer for pathology. I am also the Institutional PI for Pathology for COG. As member of the COG, I am part of a panel of International Pediatric Liver tumor Classification and member of the COG Liver tumor Subcommittee. I also manage the weekly Tumor Board at CHP.
- Pediatric Liver and small bowel transplant pathology and pathology of post-transplant complications including posttransplant lymphoproliferative diseases and smooth muscle tumors.
- Pediatric GI diseases specifically inflammatory bowel disease (part of CHP IBD division), Intractable diarrheas of infancy and Hirschsprung's disease
- Pediatric medical renal diseases
- Pediatric infectious diseases
Hepatoblastoma and Other Liver Diseases
I have been studying the interactions of beta-catenin and met in hepatoblastomas, a group of uncommon liver tumors of childhood. This study has been done in collaboration with Dr. S.P. Monga. Our results show that there is a role for beta-catenin and met interactions in hepatoblastoma and that there may be alterations in the expressions of these proteins as a result of chemotherapy. We have also demonstrated a role for epidermal growth factor in these tumors. I was also involved in the study of gene expression analysis of these tumors and our efforts have resulted in a manuscript that has been published in Hepatology. The studies on hepatoblastomas have been ongoing and I have expanded the immunohistochemical profile of these tumors. I was awarded a Children’s Oncology Group Young Investigator travel award to work with Dr. Milton Finegold from Texas Children's Hospital over a two year span. The first part of the award involved analysis of cases of hepatoblastoma that have been encountered in the Pediatric Cancer study group over the last decades. I began this project with a McAdams Travel stipend awarded by the Society for Pediatric Pathology (SPP) in 2007 July.
I hope to continue to study further the morphologic characteristics of these tumors and I am currently a central reviewer for hepatoblastoma study that is ongoing at the Children’s Oncology Group. I also am in the process of studying the same B-catenin interaction in other liver tumors and non-neoplastic liver diseases in collaboration with Dr. S.P. Monga. We have also had a recent publication on N-terminal and C-terminal beta-catenin in hepatoblastomas and are currently looking into mouse models of knockouts that have tumors resembling hepatoblastomas in collaboration with scientists in San Francisco. The manuscript was published in Gastroenterology in 2014 with cover page illustration and editorial.
I have also been looking into the interactions of glutamine synthetase and glypican-3 with beta-catenin in hepatoblastomas, hepatocellular carcinomas in children and in non-neoplastic metabolic and drug related liver diseases, the preliminary results of which were presented at the Annual Society for Pediatric Pathology Meeting in March 2008 and March 2011. I am in the process of completing my manuscripts on some of these topics. We have also presented data on markers to differentiate hepatoblastomas and pediatric HCC at the Annual SPP meeting in 2012 at Vancouver. We have also published our experience with liver transplantation for hepatoblastomas in collaboration with Dr. R. Sindhi and are presenting our data on all liver tumor transplant experience at the Transplant Congress in July 2014. I have also recently studies the role of the EGFR pathway in subgroups of hepatoblastomas cases, a work that was presented at AASLD Liver Meeting in 2014. I have also reviewed a group of teratoid hepatoblastomas presented at The Society for Pediatric Pathology meeting in 2015.
As a result of all my work in hepatoblastomas and due to my COG Young Investigator work, I am now on the Children's Oncology Group Liver Subcommittee and was involved in the implementation of the new therapeutic COG Study on hepatoblastoma treatment and am a reviewer with Dr. Finegold on the new study of these tumors (AHEP0731). The goal of this study is to analyze prognostic features and see if therapy can be based on morphologic predictors. The study is ongoing with data collection at present. I am also the senior study pathologist for the upcoming International Trial on Pediatric hepatoblastomas and hepatocellular carcinomas (PHITT trial), a study that will be spanning 5 continents with attempt at standardization of tumor diagnosis and management universally.
I was also an Invited Faculty at the International Consensus Classification meeting of Pediatric Liver tumors and was invited to sessions at Los Angeles in 2011 and attended the second session in Gdansk, Poland in April 2012. A manuscript has been published in Modern Pathology, updating the new classification system for pediatric liver tumors. I am also mentoring the Pediatric GI Fellow in the study of regeneration in pediatric liver diseases with use of novel markers such as LGR5. This study is in collaboration with Dr. G. Michalopoulos. Preliminary data has been presented at the ASIP meeting in 2015.
I have also been involved in molecular mechanisms of biliary atresias in collaboration with Dr. Rakesh Sindhi. We have identified a role for ARF6 gene in biliary atresia pathogenesis, currently in press at PLOS1 and are in the process of identifying other players in this common pediatric cholestatic disease. ChiLDReN network: I am a funded coinvestigator on a NIH grant for study of pediatric liver diseases as part of the ChiLDReN network (a multicenter trial for study of pediatric cholestatic liver disease) with Dr. Rob Squires as the P.I. This work involves review of all liver biopsies of children with cholestasis enrolled in these studies with a group of Pathologists from several Institutions.
I have a special interest in pediatric sarcomas and have previously studied primitive neuroectodermal tumors (PNET) and epithelioid sarcomas in children. I was a reviewer for a new pilot project of the Children's Oncology Group (COG) on Ewing's sarcoma/PNET (AEWS02P1). This is a pilot study of the effects of anti-angiogenesis agents on patients with advanced stage Ewing’s sarcoma/PNET. This study is now completed and a manuscript is now published. I was also involved in another pilot COG study on EWS/PNET the results of which were presented at the ASCO meeting in 2011.
Myofibroblastic Lesions of Childhood
The pathology of myofibroblastic lesions is an evolving subject and recent advances in molecular aspects have shown some of these to have specific genetic abnormalities. We have been systematically reviewing our cases of myofibroblastic lesions and hope to elicit differences in the various types of myofibroblastic lesions and also study some molecular markers of oncogenesis in these lesions. We have now collected preliminary data and are in the process of evaluating the results. I have also been mentoring the Pediatric Hematology-Oncology Fellow on the study of novel markers in desmoid tumors and have just submitted a manuscript for consideration for publication.
Pediatric GI Pathology
I am interested in pediatric inflammatory bowel disease and have studied the tumor MUC1 protein expression in the epithelium of inflamed bowel in IBD in collaboration with Dr. Olivera Finn from Department of immunology, UPMC. This data has been published in Pediatric and developmental Pathology 2010. I am also a co-investigator and collaborator with Dr. Finn on a NIH grant that just ended and a new grant proposal being submitted. This project has resulted in a publication in Cancer Prevention Research in 2010 and one in Oncoimmunology 2012. I am also a member of the IBD-LIVE group which involves a multidisciplinary, multicenter discussion of difficult patients for management with a goal of publication of select cases in IBD journal.
I have also recently reviewed our experience with pediatric autoimmune enteropathy and tufting enteropathy both of which are published in Pathology journals. I am the Institutional Pathologist on the PROTECT study for ulcerative colitis, a National collaborative study and on a multi-institutional grant application for study of Rare intestinal diseases with Dr. Martin from San Francisco. I am also collaborating with researchers at Emory University on the study of novel markers in microvillus inclusion disease.
Pediatric Germ Cell Tumors
This is an ongoing study with our Research Fellow Eumenia Castro and involves immunohistochemical analysis of pediatric germ cell tumors with the aim of finding markers to detect foci of yolk sac carcinoma in these mixed tumors. This data has been presented and a manuscript is in the works. On a parallel note I am also studying the utility of glypican 3 in pediatric sarcomas especially since there have been reports of a role in myogenesis and in some Wilms tumors.
Pediatric small bowel transplantation
I have been involved with Dr. Rakesh Sindhi and Dr. Kyle Soltys on multiple projects in small bowel transplants with the goal of elucidating the cellular mechanisms of transplant rejection. We have stained and done gene expression studies on transplant recipients and I have scored serial biopsies on rejectors and non-rejectors for macrophages and plasma cells as well as other markers such as granulysin, CCL4, CD14. CD138 and CD163. The role of macrophage in small bowel transplant has been accepted for publication in American Journal of Pathology. Other manuscripts have also resulted and a grant application has been submitted.
- MBBS, Mumbai University, India
- MD Pathology, Mumbai University, India
- Diplomate of National Board, New Delhi D.N.B. Pathology
- American Board of Pathology, Anatomic Pathology/Clinical Pathology
- American Board of Pathology, Pediatric Pathology
SpecialtiesPediatric Pathology – Washington University School of Medicine/St. Louis Children's Hospital/Barnes-Jewish Hospital
Awards and Honors
- Children's Oncology Group Young Investigator Award -2006 – Study of hepatoblastomas and Pediatric HCC
- McAdam's Travel Award, Society for Pediatric Pathology, 2007.
- Society for Pediatric Pathology
- Indian Association of Pathologists and Microbiologists
- United States and Canadian Academy of Pathologists
- Children's Oncology Group, Bone Sarcoma and Rare Tumors Committee
- Association of Indian Pathologists of North America
Selected PublicationsView Dr. Ranganathan's publications on PubMed
- Cruz RJ Jr, Ranganathan S, Mazariegos G, Soltys K, Nayyar N, Sun Q, Bond G, Shaw PH, Haberman K, Krishnamurti L, Marsh JW, Humar A, Sindhi R. Analysis of national and single-center incidence and survival after liver transplantation for hepatoblastoma: New trends and future opportunities. Surgery. 2013 Feb;153(2):150-9. PMID: 23331862.
- Zhou S, Ranganathan S, Venkatramani R, Gomulia E, Wang L. Teratoid Hepatoblastoma with Abundant Cholangioblastic Component in a Child with Full Trisomy 13: a Rare Case Report. Pediatr Dev Pathol.2013 16(6):438-41 PMID: 23927400.
- López-Terrada D, Alaggio R, de Dávila MT, Czauderna P, Hiyama E, Katzenstein H, Leuschner I, Malogolowkin M, Meyers R, Ranganathan S, Tanaka Y, Tomlinson G, Fabrè M, Zimmermann A, Finegold MJ. Towards an international pediatric liver tumor consensus classification: proceedings of the Los Angeles COG liver tumors symposium. Mod Pathol. 2014 Mar;27(3):472-91 PMID: 24008558.
- Singhi AD, Goyal A, Davison JM, Regueiro MD, Roche RL, Ranganathan S. Pediatric autoimmune enteropathy: an entity frequently associated with immunodeficiency disorders. Mod Pathol. 2014 Apr;27(4):543-53. PMID: 24051695
- Ranganathan S, Schmitt LA, Sindhi R. Tufting enteropathy revisited: the utility of MOC31 (EpCAM) immunohistochemistry in diagnosis. Am J Surg Pathol. 2014 Feb;38(2):265-72. PubMed PMID: 24418860
- Venkat VL, Ranganathan S, Mazariegos GV, Sun Q, Sindhi R. Recurrence of primary sclerosing cholangitis in pediatric liver transplant recipients. Liver Transpl. 2014 Feb 24. doi: 10.1002/lt.23868. [Epub ahead of print] PMID: 24634351
- Trejo-Bittar HE, Radder JE, Ranganathan S, Srinivasan A, Madan-Khetarpal S, Reyes-Múgica M. Clear Cell Sarcoma of the Kidney in a Child with Fanconi Anemia. Pediatr Dev Pathol. 2014 Apr 15. [Epub ahead of print] PubMed PMID: 24735155.
- Tao J, Calvisi DF, Ranganathan S, Cigliano A, Zhou L, Singh S, Jiang L, Fan B, Terracciano L, Armeanu-Ebinger S, Ribback S, Dombrowski F, Evert M, Chen X, Monga SP. Activation of β Catenin and Yap1 in Human Hepatoblastoma and Induction of Hepatocarcinogenesis in Mice. Gastroenterology. 2014 Sept; 147(3):690-701 doi: 10.1053/j.gastro.2014.05.004. Epub 2014 May 14. PubMed PMID: 24837480. (co first author)
- Ng VL, Haber BH, Magee JC, et al; Childhood Liver Disease Research and Education Network (CHiLDREN). Medical status of 219 children with biliary atresia surviving long-term with their native livers: results from a North American multicenter consortium. J Pediatr. 2014 Sep;165(3):539-546.e2. doi: 10.1016/j.jpeds.2014.05.038. Epub 2014 Jul 9. Erratum in: J Pediatr. 2015 Jan;166(1):211. PubMed PMID: 25015575; PubMed Central PMCID: PMC4144331.
- Regueiro MD, Greer JB, Binion DG, et al; IBD LIVE Physician Group. The inflammatory bowel disease live interinstitutional and interdisciplinary videoconference education (IBD LIVE) series. Inflamm Bowel Dis. 2014 Oct;20(10):1687-95. doi: 10.1097/MIB.0000000000000187. PubMed PMID: 25167213.
- Ranganathan S, Ashokkumar C, Ningappa M, Schmitt L, Higgs BW, Sindhi R. The Transcription Factor, T-bet, Primes Intestine Transplantation Rejection and Is Associated With Disrupted Mucosal Homeostasis. Transplantation. 2015 Apr;99(4):890-4. PMID: 25340608.
- Courtney R, Ranganathan S. Simultaneous Adrenocortical Carcinoma and Neuroblastoma in an Infant With a Novel Germline p53 Mutation. J Pediatr Hematol Oncol. 2014 Nov 4. [Epub ahead of print] PMID: 25374282.
- Fan Y, Fang X, Tajima A, Geng X, Ranganathan S, Dong H, Trucco M, Sperling MA. Evolution of hepatic steatosis to fibrosis and adenoma formation in liver-specific growth hormone receptor knockout mice. Front Endocrinol (Lausanne). 2014 Dec 18;5:218. doi: 10.3389/fendo.2014.00218. eCollection 2014. PubMed PMID: 25566190.
- McFadden K, Ranganathan S. Pathology of the gallbladder in a child with metachromatic leukodystrophy. Pediatr Dev Pathol. 2015 May-Jun;18(3):228-30. PMID: 25569213.
- Venkat VL, Ranganathan S, Sindhi R. The challenges of liver transplantation in children with primary sclerosing cholangitis. Expert Rev Gastroenterol Hepatol. 2015 Mar;9(3):289-94. PMID: 25592492
- Ningappa M, Min J, Higgs BW, Ashokkumar C, Ranganathan S, Sindhi R. Genome-wide association studies in biliary atresia. Wiley Interdiscip Rev Syst Biol Med. 2015 May 11. [Epub ahead of print] PMID: 25963027.
- Harmon CM, Azzuqa AA, Ranganathan S, Mahmood B, Good M. Mid-Aortic Syndrome in a Preterm Infant: A Rare Cause of Hypertension. J Pediatr. 2015 May 30. [Epub ahead of print] PubMed PMID: 26037732.
- Ranganathan S. Hepatoblastomas. In Liver Pathology - Consultant Pathology Series. Editors. Kakar S, Ferrell L. Demos Medical Publishing, NY. 2011.
- White FV, Ranganathan S. Pathology of Small Bowel transplantation. In Ed. Liapis, et al. Pathology of Solid Organ Transplantation. Springer 2011.
- Ranganathan S. Small Bowel Transplant Pathology. In Transplant Pathology. Co-editor. Amyrsis Diagnostic Pathology Series. November 2013.
- Ranganathan S. Pediatric Small Bowel and Liver transplantation Pathology in “Pathology of Pediatric Gastrointestinal and Liver Diseases”. 2nd ed. Springer Ed Russo P. et al. Sept 2014
- Ranganathan S. “Congenital Tumors” In “Pediatry Autopsy Manual” Ed. Cohen and Scheimberg Cambridge University Press. Sept 2014.