Thomas Tracy, MD, MS
Professor and Vice Chair of Surgery and Professor of Pediatrics
Work: +1 401-444-7605
At critical points in chronic liver injury the potential for liver repair is lost. Timely surgical and medical treatment, however, initiates liver repair in infants, children, and adults, interrupting the cycle of inflammation and hepatic fibrosis. The subsequent cellular regulation of matrix protein degradation and resolution of injury-dependent fibrosis is unknown. The long-term goals of our studies are to define the molecular mechanisms required for ordered matrix resorption and liver repair.
BiographyThomas F. Tracy, Jr is Vice Chairman of the Department of Surgery and Professor of Surgery and Pediatrics. He is the Residency Director in Pediatric Surgery as well as Pediatric Surgeon-in-Chief, Hasbro Children's Hospital. After training in surgery at MCV and pediatric surgery at Columbia, Dr. Tracy came to Brown as an NIH funded investigator who has authored well over 100 peer-reviewed manuscripts. He is a study section ember for NIDDK and a director of the American Board of Surgery and the Pediatric Surgery Board of the ABS. He is on the Executive Board of the American Pediatric Surgical Association and The Pediatric Surgery Council of the American College of Surgeons. Dr. Tracy is an elected member of the leading national surgical societies. His research interests examine hepatic repair mechanisms following liver injury that currently focus on the cellular mechanisms for matrix metalloproteinase activity required for successful liver repair.
Research DescriptionAt critical points in chronic liver injury the potential for liver repair is lost. Timely surgical and medical treatment, however, initiates liver repair in infants, children, and adults, interrupting the cycle of inflammation and hepatic fibrosis. The subsequent cellular regulation of matrix protein degradation and resolution of injury-dependent fibrosis is unknown. The long-term goals of our studies are to define the molecular mechanisms required for ordered matrix resorption and liver repair without scar. Specific aims have been designed to test the hypothesis that repair, resolution of scar, and the restoration of hepatic architecture depend on coordinated regulatory mechanisms of matrix degradation through matrix metalloproteinase (MMP) and tissue inhibitor of MMP (TIMP) gene expression, cellular localization, and most importantly, biologic activity. Further, we propose that Kupffer cells (KC), the resident macrophage population, have a central role in the inflammatory and fibrogenic regulation of liver repair after chronic injury. Specific Aim 1 addresses the molecular and cellular mechanisms of reversible hepatic fibrosis and those of delayed matrix resorption. A unique rat model of reversible biliary obstruction will simulate early, intermediate, and late, near end stage cholestatic liver injury. This model allows biliary decompression to initiate liver repair. The effect of injury duration on matrix (Collagen I, III, IV, elastin, laminin), MMP (1,2,8,9,13,14), and TIMP (1,2) mRNA and protein expression will be measured in whole liver and cells using new methods of laser capture microdissection. Changes in these profiles will be directly applied to the mechanism of matrix resorption by simultaneous measurement of MMP activity by in-gel and in situ zymography. Specific Aim 2 mechanistically tests the hypothesis that KC are in vivo regulators of matrix metabolism. Through strategies of KC depletion/inactivation by gadolinium or Dexa-Man10-HSA targeted dexamethasone during repair, matrix resorption, regulatory cytokine profiles, and MMP-TIMP activity will be localized in cells and measured. In Specific Aim 3 we will establish the effect of progressive injury on the in vitro capacity of isolated hepatic macrophages (Mf) to express specific MMP and fibrogenic/antifibrogenic cytokine (TGFb, IL1, 6, 10) profiles during repair. KC inactivation and MMP stimulation/suppression strategies will isolate the net collagenolytic activity of Mf. Apart from broad clinical implications for the treatment of cholestatic or other chronic liver diseases, these studies have the potentialto be the first studies to identify key molecular mechanisms for successful repair after progressive liver injury. They have the potential to yield targets for therapy to promote liver repair or rescue patients approaching end stage liver disease.
Grants and AwardsThyssen Foundation Fellowship Grant for US Israel Germany Collaboration
Baylor College of Medicine
Design of and cell membrane interaction with synthetic high density
Alpha Omega Alpha Honor Society, Brown University (2009)
Included in Best Doctors in America 2009-2010 database.
Sackler School of Medicine
Tel Aviv University, Israel (1981)
Distinguished Alumnus, Sackler School of Medicine, New York, NY
AffiliationsAmerican Surgical Association
Fellow, American College of Surgeons
American Pediatric Surgical Association
Association of Pediatric Surgery Training Program Directors
The Halsted Society Fellow, American Academy of Pediatrics, Member - Surgical Section
Society of University Surgeons
New England Surgical Society
Surgical Biology Club III, American College of Surgeons
Boston Surgical Society
American Association for the Study of Liver Diseases
American Society for Cell Biology
Gastroenterology Research Group
Association for Academic Surgery
Children's Cancer Study Group (1989-1994)
Pediatric Oncology Group (1994-1999)
Children's Oncology Group (1999-Present)
Pediatric Surgery Biology Club, American College of Surgeons
Humera Surgical Society
Rhode Island Chapter American College of Surgeons
Providence Surgical Society
Funded Research"Oncogene Expression in Cholestatic Livers." IN 124504381.
American Cancer Society, 1988-91.
"The Influence of Diminished Uterine Blood Flow, Fetal Tissue PO2, and Growth Factor Expression on the Development of Intrauterine Growth Retardation."
Fleur-de-Lis Foundation, 1990.
"Proto-oncogene and Growth Factor Expression During Cholestatic Liver Injury."
Fleur-de-Lis Foundation, 1990.
"The Effects of Cholestasis on Regulatory Gene Expression and DNA Synthesis in Cultured Hepatocytes."
Fleur-de-Lis Foundation, 1991.
"Reversible Bile Duct Obstruction Without Bilioenteric Anastomosis: A New Model to Study Regulatory Gene Expression During Cholestatic Liver Injury and Repair."
Fleur-de-Lis Foundation, 1991.
Regulation of Liver Gene Expression and Transcriptional Transactivation: "Effects of Cholestatic Liver Injury and Repair Following Biliary Decompression."
Fleur-de-Lis Foundation, 1992.
"Cellular and Molecular Mechanisms of Liver Repair After Biliary Reconstruction," DK 46831.
National Institutes of Health, National Institute of Diabetes, Digestive and Kidney Diseases. May 1, 1994-November 30, 2001.
$347,912, direct costs.
"Prevention of TPN-Cholestasis with Cholecystokinin," FD-R-001449-03.
Food and Drug Administration, 1997-2002,
$36,159, current year.
"Minimally invasive surgery in children with cancer," CA 65175.
National Institutes of Health, National Cancer Institute, 1994, end 12/94 with transfer to the Pediatric Oncology Group.
"A case control study of gastroschisis and small intestinal defects in relation to maternal decongestant use,"
St. Louis University IRB8219. Funds from Marion, Merrell - Dow, Warner - Wellcome, Procter and Gamble, 1995.
Sloan Epidemiology Unit, Boston University School of Medicine.
"Molecular and cellular control of the inflammatory response to liver injury," DK 44305.
National Institutes of Health, National Institute of Diabetes, Digestive and Kidney Diseases, 1996.
"The role of stellate cells in hepatic inflammation." Merit Review.
Department of Veterans Affairs, 1997,
"Prevention of TPN-Cholestasis with Cholecystokinin," FDA-OP-97-1.
Food and Drug Administration,
$38,817 total costs, 1997.
"Integrated Research Training Program and Trauma-Inflammation Biology."
National Institutes of Health, 1999.
Research Faculty, co-investigator.
"New England Pediatric Oncology Consortium," 5 U10 CA29293-21.
National Cancer Institute, 2001.
"Neutrophil-Kupffer Cell Interaction During Infection," R01 DK 46831-06.
Department of Health and Human Services.
$1,386,000 total costs, 2003-2008.
"Injury Free Coalition for Kids."
Columbia University School of Public Health.
Injury Prevention Center, Rhode Island Hospital.
Current T32: "Trauma and Inflammation Research Training Grant." 1T32GM065085-1A1.
National Institutes of General Medical Sciences, 7/1/04 6/30/09.
Current RO1:"Cellular Mechanisms of Matrix Regulation and Liver Repair," 2R01 DK046831-06.
National Institutes of Health, National Institute of Diabetes, Digestive and Kidney Diseases, 12/01/01-11/30/06.
$1,025,000, direct costs.
Dr. Tracy is the Course Director for the First Deluca Symposium for Pediatric Surgery as well as Level V, BioMed 410-Pediatric Surgery and Lefel III-Pediatric Surgery.
- Gehring S, Dickson EM, San Martin ME, van Rooijen N, Papa EF, Harty M, Tracy TF Jr, Gregory SH: Kupffer cells abrogate cholestatic liver injury in mice. Gastroenterology. 2006 March;130(3):810-22. (2006)
- Kwon A, Sorrells DL Jr, Kurkchubasche AG, Cassese J, Tracy TF Jr, Luks FI: Isolated computed tomography diagnosis of pulmonary contusion does not correlate with increased morbidity. J. Pediatr Surg. 2006 Jan;41(1):87-82. (2006)
- Chang J, Carr SR, Tracy TF Jr, Luks FI: Port insertion and removal techniques to minimize premature rupture of the membranes in endoscopic fetal surgery. J Pediatr Surg 2006 May;41(5):905-9. (2006)
- Truitt AK, Carr SR, Cassese J, Kurkchubasche AG, Tracy TF Jr, Luks FI: Perinatal management of congenital cystic lung lesions in the age of minimally invasive surgery. J Pediatr Surg. 2006 May;41(5):893-6 (2006)
- Harty MW, Huddleston HM, Papa EF, Puthawala T, Tracy AP, Ramm GA, Gehring S, Gregory SH, Tracy TF Jr: Repair after cholestatic liver injury correlates with neutrophil infiltration and matrix metalloproteinase 8 activity. Surgery. 2005 Aug; 138(2):313-20. (2005)
- Truitt AK, Sorrells DL Jr, Halvorson E, Starring J, Kurkchubasche AG, Tracy TF Jr, Luks FI: Pulmonary embolism: which pediatric trauma patients are at risk? J Pediatr Surg. 2005 Jan; 40(1):124-7. (2005)
- Lui F, Gormley P, Sorrells DL Jr, Biffl WL, Kurkchubasche AG, Tracy TF Jr, Luks FI: Pediatric trauma patients with isolated airway compromise or Glasgow Coma Scale less than 8: does immediate attending surgeon's presence upon arrival make a difference? J Pediatr Surg. 2005 Jan; 40(1):103-6. (2005)
- Vrochides DV, Sorrells Jr DL, Kurkchubasche, AG, Tracy Jr TF, Luks FI: Is there a role for routine, preoperative ERCP for suspected choledocholithiasis in children?" Arch Surg 140:359-361, 2005. (2005)
- Luks FI, Carr SR, DePaepe ME, Tracy TF Jr.: What and why the pediatric surgeon should know about twin-to-twin transfusion syndrome. J Pediatr Surg. 2005 Jul; 40(7):1063-9. (2005)
- Teitelbaum DH, Tracy TF Jr, Aouthmany MM, Llanos A, Brown MB, Yu S, Brown MR, Shulman RJ, Hirschl RB, Derusso PA, Cox J, Dahlgren J, Groner JI, Strouse PJ: Use of Cholecystokinin-Octapeptide for the Prevention of Parenteral Nutrition-Associated Cholestasis. Pediatrics. 2005 May; 115(5):1332-40. (2005)
- Spencer AU, Yu S, Tracy TF, Aouthmany MM, Llanos A, Brown MB, Brown M, Shulman RJ, Hirschl RB, Derusso PA, Cox J, Dahlgren J, Strouse PJ, Groner JI, Teitelbaum DH, Stechmiller JK: Parenteral nutrition-associated cholestasis in neonates: multivariate analysis of the potential protective effect of taurine. J Parenter Enteral Nutr. 2005 Sep-Oct; 29(5):337-43. (2005)
- Carr SR, Luks FI, Tracy TF, Jr., Plevyak M.: Antenatal Necrotic Injury in Severe Twin-to-Twin Transfusion Syndrome. A Case and Review. Fetal Diagn Ther 19:370-372, 2004. (2004)
- Luks FI, Carr SR, Plevyak M, Craigo SD, Athanassiou A, Ralston SJ, Tracy Jr TF: Limited prognostic value of a staging system for twin-to-twin transfusion syndrome. Fetal Diagn Ther 19:301-304, 2004. (2004)
- Bussey JG, Luks F, Carr SR, Plevyak M, Tracy TF Jr: Minimal-access fetal surgery for twin-to-twin transfusion syndrome. Surg Endosc. 18:83-86, 2004. (2004)
- Oka T, Kurkchubasche AG, Bussey JG, Wesselhoeft CW Jr, Tracy TF Jr, Luks FI: Open and laparoscopic appendectomy are equally safe and acceptable in children. Surg Endosc 18: 242-5, 2004 (2004)
- Biffl WL, Schiffman JD, Harrington DT, Sullivan J, Tracy TF Jr, Cioffi WG: Legal prosecution of alcohol-impaired drivers admitted to a level I trauma center in Rhode Island. J Trauma. 56:24-29, 2004. (2004)
- Fukudome E, Levin M, Pappa E, Kurkchubasche A, Roggin K, Tracy T: Matrix regulation and MMP activity during liver repair is macrophage dependent. J Am Coll Surg: 197:3 S50, 2003. (2003)
- Harel Z, Tracy TF Jr, Bussey JG: Small Bowel Obstruction in an Adolescent with Pelvic Inflammatory Disease due to Chlamydia Trachomatis. J Pediatr Adolesc Gynecol.16:125-128, 2003. (2003)
- Tracy TF Jr, Crawford LS, Krizek TJ, Kern KA: When Medical Error Becomes Medical Malpratice: The Victims and the Circumstances. Arch of Surg 138: 447-454, 2003. (2003)
- Tracy, TF Jr.: The next steps for pediatric tracheal reconstruction. Ann Thorac Surg 74:306-7, 2002. (2002)
- Tomicic JT, Luks FI, Shalon L, Tracy TF: Laparoscopic gastrostomy in infants and children. Eur J Pediatr Surg. 12:107-110, 2002. (2002)
- Luks FI, Carr SR, Tracy TF Jr: Intestinal atresia associated with twin-twin transfusion syndrome. J Pediatr Surg.36:1105-6, 2001. (2001)
- Roggin KK, Papa EF, Kurkchubasche AG, Tracy TF Jr.: Differential expression of matrix metalloproteinase during liver repair: evidence of hepatic macrophage regulation. Surg Forum 52:503-506, 2001. (2001)
- Luks FI, Carr SR, Ponte B, Rogg JM, Tracy TF Jr. Preoperative planning with magnetic resonance imaging and computerized volume rendering in twin-to-twin transfusion syndrome. Am J Obstet Gynecol. 185:216-219, 2001. (2001)
- Kokoska ER, Minkes RK, Silen ML, Langer JC, Tracy TF Jr, Snyder CL, Dillon PA, Weber TR: The effect of pediatric surgical practice on the management of children with appendicitis. Pediatrics 107:1298-1301, 2001. (2001)
- Teitelbaum DH, Tracy T: Parenteral nutrition-associated cholestasis. Semin Pediatr Surg 10:72-80, 2001. (2001)
- Phornphutkul C, Okubo T, Wu K, Harel Z, Tracy TF, Pinar H, Chen S, Gruppuso PA, Goodwin G. Aromatase P450 expression in a feminizing adrenal adenoma presenting as isosexual precocious puberty. J Clin Endocrinol Metab 86:649-652, 2001. (2001)
- Roggin KK, Kim JC, Kurkchubasche AG, Papa EF, Bezeredis AM, Tracy TF: Macrophage phenotype during cholestatic injury and repair: the persistent inflammatory response. J Pediatr Surg 36:220-228, 2001. (2001)
- Roggin KK, Chwals WJ, Tracy TF: Institutional Review Board approval for prospective experimental studies on infants and children. J Pediatr Surg 36:205-208, 2001. (2001)
- Kurkchubasche AG, Panepinto JA, Tracy TF Jr, Thurman GW, Ambruso DR: Clinical features of a human Rac2 mutation: a complex neutrophil dysfunction disease. J Pediatr 139:141-147, 2001. (2001)