Theo Heller, M.D.


Chief, Translational Hepatology Unit

Liver Diseases Branch
LIVER DISEASES BRANCH
NIDDK, National Institutes of Health
Building 10 , Room 9C432B
10 Center Dr.
Bethesda, MD 20814
Tel: 301-402-7147
Fax: 301-402-0491
Email: theoh@intra.niddk.nih.gov

Theo Heller, M.D.

Education / Previous Training and Experience:
B.Sc., University of Cape Town, 1983
M.D., University of the Witwatersrand, 1989

Nancy Nossal Mentorship Award, 2008
NIDDK Early Career Investigator Award, 2010


Research Statement:

Liver disease presents a unique confluence of many disciplines, in both the basic science and clinical realms. In addition there are many unanswered questions in terms of basic hepatic biology and the development of liver disease. The laboratory is interested in testing hypotheses in clinical situations which can be translated into laboratory projects, which in turn might lead to fundamental biologic insights and improved disease management. A philosophical approach is that clinical observations can sometimes best be explained at the bench and that human disease investigation is in many ways better than a model, it is a direct study of authentic biology. It is believed that human disease is a window into biology and that by studying diseases, some rare, derived concepts may be extrapolated to a far broader understanding of biologic principals.

The laboratory focus is on the intersection of the innate immune system and hepatic damage and repair. The clinical focus is on non-cirrhotic portal hypertension, including nodular regenerative hyperplasia. Patients with Chronic Granulomatous Disease, Sickle Cell Disease, Turner Syndrome, and sporadic nodular regenerative hyperplasia drive both the laboratory and clinical research. These projects are the result of significant collaborations with multiple other investigators. In addition there is a long standing interest in hepatitis D, acute hepatitis C, and congenital hepatic fibrosis.

All of the work is carried out with the direct mentorship of T. Jake Liang, M.D., the branch chief. The clinical projects also benefit from the involvement and direction of Jay Hoofnagle, M.D.



Selected Publications:

Leiding JW, Freeman AF, Marciano BE, Anderson VL, Uzel G, Malech HL, Deravin S, Wilks D, Venkatesan AM, Zerbe CS, Heller T, Holland SM. Corticosteroid therapy for liver abscess in chronic granulomatous disease. Clin Infect Dis. 2011 Dec 9. [Full Text/Abstract]

Kandiah E, Watts NR, Cheng N, Cardone G, Stahl SJ, Heller T, Liang TJ, Wingfield PT, Steven AC. Cryo-EM study of Hepatitis B virus core antigen capsids decorated with antibodies from a human patient. J Struct Biol. 2012 Jan;177(1):145-51. Epub 2011 Oct 25. [Full Text/Abstract]

Gunay-Aygun M, Turkbey BI, Bryant J, Daryanani KT, Gerstein MT, Piwnica-Worms K, Choyke P, Heller T, Gahl WA. Hepatorenal findings in obligate heterozygotes for autosomal recessive polycystic kidney disease. Mol Gen Metab. 2011 Dec;104(4):677-81. Epub 2011 Sep 8. [Full Text/Abstract]

Arora M, Uzel G, Shea YR, Kleiner DE, Holland SM, Heller T. GI involvement in disseminated Mycobacterium genavense: endoscopy and histology. Gastrointest Endosc. 2011 Sep;74(3):688-90. Epub 2011 Jul 26. [Full Text/Abstract]

Sandler NG, Koh C, Roque A, Eccleston JL, Siegel RB, Demino M, Kleiner DE, Deeks SG, Liang TJ, Heller T, Douek DC. Host response to translocated microbial products predicts outcomes of patients with HBV or HCV infection. Gastroenterology. 2011 Oct;141(4):1220-30, 1230.e1-3. Epub 2011 Jul 2. [Full Text/Abstract]

Shin EC, Park SH, Demino M, Nascimbeni M, Mihalik K, Major M, Veerapu NS, Heller T, Feinstone SM, Rice CM, Rehermann B. Delayed induction, not impaired recruitment, of specific CD8+ T cells causes the late onset of acute hepatitis C. Gastroenterology. 2011 Aug;141(2):686-95, 695.e1. Epub 2011 May 18. [Full Text/Abstract]

O’Brien K, Font-Montgomery E, Lukose L, Bryant J, Piwnica-Worms K, Edwards H, Riney L, Garcia A, Daryanani K, Choyke P, Mohan P, Heller T, Gahl WA, Gunay-Aygun M. Congenital hepatic fibrosis and portal hypertension in autosomal dominant polycystic kidney disease. J Pediatr Gastroenterol Nutr. 2012 Jan;54(1):83-9. [Full Text/Abstract]

Weinstein DH, Childs R, Heller T. Giant duodenal ectasia. Clin Gastroenterol Hepatol. 2011 Jun;9(6):A24. Epub 2011 Jan 28. [Full Text/Abstract]

Loomba R, Rivera MM, McBurney R, Park Y, Haynes-Williams V, Rehermann B, Alter HJ, Herrine SK, Liang TJ, Hoofnagle JH, Heller T. The natural history of acute hepatitis C: clinical presentation, laboratory findings and treatment outcomes. Aliment Pharmacol Ther. 2011 Mar;33(5):559-65. Epub 2010 Dec 29. [Full Text/Abstract]

Veerapu NS, Raghuraman S, Liang TJ, Heller T, Rehermann B. Sporadic Reappearance of Minute Amounts of HCV RNA after Successful Therapy Stimulates Cellular Immune Responses. Gastroenterology. 2011 Feb;140(2):676-685.e1. Epub 2010 Oct 30. [Full Text/Abstract]

Kuhns DB, Alvord WG, Heller T, Feld JJ, Pike KM, Marciano BE, Uzel G, DeRavin SS, Priel DA, Soule BP, Zarember KA, Malech HL, Holland SM, Gallin JI. Residual NADPH oxidase and survival in chronic granulomatous disease. N Engl J Med. 2010 Dec 30;363(27):2600-10. [Full Text/Abstract]

Uzel G, Orange JS, Poliak N, Marciano BE, Heller T, Holland SM. Complications of Tumor Necrosis Factor-α Blockade in Chronic Granulomatous Disease-Related Colitis. Clin Infect Dis. 2010 Dec 15;51(12):1429-34. Epub 2010 Nov 8. [Full Text/Abstract]

Chetty-John S, Piwnica-Worms K, Bryant J, Bernardini I, Fischer RE, Heller T, Gahl WA, Gunay-Aygun M. Fibrocystic disease of liver and pancreas; under-recognized features of the X-linked ciliopathy oral-facial-digital syndrome type 1 (OFD I). Am J Med Genet A. 2010 Oct;152A(10):2640-5. [Full Text/Abstract]

Noureddin M, Kleiner DE, Gharib AM, Bratslavsky G, Heller T. To resect or not to resect? That is the question. Gut. 2011 Sep;60(9):1177, 1235. Epub 2010 Sep 24. [Full Text/Abstract]

Feld JJ, Modi AA, El-Diwany R, Rotman Y, Thomas E, Ahlenstiel G, Titerence R, Koh C, Cherepanov V, Heller T, Ghany MG, Park Y, Hoofnagle JH, Liang TJ. S-Adenosyl Methionine Improves Early Viral Responses and Interferon-Stimulated Gene Induction in Hepatitis C Nonresponders. Gastroenterology. 2011 Mar;140(3):830-9. Epub 2010 Sep 17. [Full Text/Abstract]

Kucirka LM, Farzadegan H, Feld JJ, Mehta SH, Winters M, Glenn JS, Kirk GD, Segev DL, Nelson KE, Marks M, Heller T, Golub ET. Prevalence, correlates, and viral dynamics of hepatitis delta among injection drug users. J Infect Dis. 2010 Sep 15;202(6):845-52. [Full Text/Abstract]

von Rosenvinge EC, Koh C, Holland SM, Heller T. When to leave a stone unturned ... Gut. 2010 Aug;59(8):1036, 1100. Epub 2010 Jun 10. [Full Text/Abstract]

Feld JJ, Lutchman GA, Heller T, Hara K, Pfeiffer JK, Leff RD, Meek C, Rivera M, Ko M, Koh C, Rotman Y, Ghany MG, Haynes-Williams V, Neumann AU, Liang TJ, Hoofnagle JH. Ribavirin Improves Early Responses To Peginterferon Through Improved Interferon Signaling. Gastroenterology. 2010 Jul;139(1):154-62.e4. Epub 2010 Mar 17. [Full Text/Abstract]

Rotman Y, Borg BB, Soza A, Feld JJ, Modi AA, Loomba R, Lutchman G, Rivera E, Doo E, Ghany MG, Heller T, Neumann AU, Liang TJ, Hoofnagle JH. Low- and standard-dose peginterferon alfa-2a for chronic hepatitis C, genotype 2 or 3: efficacy, tolerability, viral kinetics and cytokine response. Aliment Pharmacol Ther. 2010 May;31(9):1018-27. Epub 2010 Jan 16. [Full Text/Abstract]

Sakiani S, Koh C, Heller T. Glowing in the dark: not always a bad thing. Gastroenterology. 2010 Mar;138(3):e7-8. Epub 2010 Jan 31. [Full Text/Abstract]

Koh C., Kleiner D, Heller T. Clinical Challenges and Images in GI: Don’t Forget To Polarize Your Lenses! Gastroenterology, 2009 Nov;137(5):e3-4. [Full Text/Abstract]

Koh C, Kleiner DE, Sherry RM, Fowler DH, Heller T. When the left got left behind. Am J Gastroenterol. 2009 Oct;104(10):2644-5. [Full Text/Abstract]

Ahlenstiel G, Titerence RH, Koh C, Feld JJ, Rotman Y, Ghany MG, Hoofnagle JH, Liang TJ, Heller T, Rehermann B. Natural killer cell function is polarized towards cytotoxicity in chronic hepatitis C in an IFN-a dependent manner. Gastroenterology, 2010 Jan;138(1):325-35.e1-2. Epub 2009 Sep 10. [Full Text/Abstract]

Laskey HL, Gopal L, Gallin JI, Holland SM, Heller T. Twenty-year follow-up of esophageal involvement in chronic granulomatous disease. Am J Gastroenterol. 2009 Sep;104(9):2368-70. [Full Text/Abstract]

von Rosenvinge EC, Gopal L, Heller T, Kohn EC, Yao MD. Rectal Fistulae Resulting from Treatment with Sorafenib and Bevacizamab. Gastrointestinal Endoscopy, 2009 Dec;70(6):1246-7. Epub 2009 Aug 15. [Full Text/Abstract]

Palmore TN, Shah NL, Loomba R, Borg BB, Lopatin U, Feld JJ, Khokar MF, Lutchman GA, Kleiner DE, Young NS, Childs R, Barrett AJ, Liang TJ, Hoofnagle JH, Heller T. Reactivation of Hepatitis B with Reappearance of Hepatitis B Surface Antigen After Chemotherapy and Immune Suppression. Clinical Gastroenterology and Hepatology, 2009 Oct;7(10):1130-7. Epub 2009 Jul 1. [Full Text/Abstract]

Gunay-Aygun M, Parisi MA, Doherty D, Tuchman M, Tsilou E, Kleiner DE, Huizing M, Turkbey B, Choyke P, Guay-Woodford L, Heller T, Szymanska K, Johnson CA, Glass I, Gahl WA. MKS3-related ciliopathy with features of autosomal recessive polycystic kidney disease, nephronophthisis, and Joubert Syndrome. J Pediatr. 2009 Sep;155(3):386-92.e1. Epub 2009 Jun 21. [Full Text/Abstract]

Koh C, Hipp JD, Kleiner DE, Heller T. Acute right upper quadrant pain: a lesson in odds. Dig Liver Dis. 2010 Jan;42(1):72-3. Epub 2009 Jun 9. [Full Text/Abstract]

Gopal L, Forbes J,Uzel G, Holland SM,Heller T. Gastrointestinal Fistulae in Chronic Granulomatous Disease. American Journal of Gastroenterology, 2009 Aug;104(8):2112-3. Epub 2009 May 12. [Full Text/Abstract]

Heller T
, Hoofnagle JH, Liang TJ, Rehermann B. Acute hepatitis C. Gastroenterology, 2009 Jun;136(7):2411. Epub 2009 May 3. [Full Text/Abstract]

von Rosenvinge EC, O'Donnell TG, Holland SM, Heller T. Chronic granulomatous disease. Inflamm Bowel Dis. 2010 Jan;16(1):9. Epub 2009 Mar 25. [Full Text/Abstract]

Turkbey B, Ocak I, Daryanani K, Font-Montgomery E, Lukose L, Bryant J, Tuchman M, Mohan P, Heller T, Gahl WA, Choyke PL, Gunay-Aygun M. Autosomal recessive polycystic kidney disease and congenital hepatic fibrosis (ARPKD/CHF). Pediatr Radiol. 2009 Feb;39(2):100-11. Epub 2008 Dec 17. [Full Text/Abstract]

Feld JJ, Hussain N, Wright EC, Kleiner DE, Hoofnagle JH, Ahlawat S, Anderson V, Hilligoss D, Gallin JI, Liang TJ, Malech HL, Holland SM, Heller T. Hepatic Involvement and Portal Hypertension Predict Mortality in Chronic Granulomatous Disease. Gastroenterology. 2008 Jun;134(7):1917-26. Epub 2008 Mar 4. [Full Text/Abstract]

Hussain N, Feld JJ, Kleiner DE, Hoofnagle JH, Garcia-Eulate R, Ahlawat S, Koziel DE, Anderson V, Hilligoss D, Choyke P, Gallin JI, Liang TJ, Malech HL, Holland SM, Heller T Hepatic abnormalities in patients with chronic granulomatous disease. Hepatology(45): 675-83, 2007. [Full Text/Abstract]

Saito S, Heller T, Yoneda M, Takahashi H, Nakajima A, Liang JT Lifestyle-related diseases of the digestive system: a new in vitro model of hepatitis C virion production: application of basic research on hepatitis C virus to clinical medicine. J Pharmacol Sci(105): 138-44, 2007. [Full Text/Abstract]

Kato T, Matsumura T, Heller T, Saito S, Sapp RK, Murthy K, Wakita T, Liang TJ Production of infectious hepatitis C virus of various genotypes in cell cultures. J Virol(81): 4405-11, 2007. [Full Text/Abstract]

Lutchman G, Modi A, Kleiner DE, Promrat K, Heller T, Ghany M, Borg B, Loomba R, Liang TJ, Premkumar A, Hoofnagle JH The effects of discontinuing pioglitazone in patients with nonalcoholic steatohepatitis. Hepatology(46): 424-9, 2007. [Full Text/Abstract]

Gunay-Aygun M, Avner ED, Bacallao RL, Choyke PL, Flynn JT, Germino GG, Guay-Woodford L, Harris P, Heller T, Ingelfinger J, Kaskel F, Kleta R, Larusso NF, Mohan P, Pazour GJ, Shneider BL, Torres VE, Wilson P, Zak C, Zhou J, Gahl WA Autosomal recessive polycystic kidney disease and congenital hepatic fibrosis: Summary statement of a First National Institutes of Health/Office of Rare Diseases conference. J Pediatr (149): 159-164, 2006. [Full Text/Abstract]

Lutchman G, Promrat K, Kleiner DE, Heller T, Ghany MG, Yanovski JA, Liang TJ, Hoofnagle JH Changes in serum adipokine levels during pioglitazone treatment for nonalcoholic steatohepatitis: relationship to histological improvement. Clin Gastroenterol Hepatol (4): 1048-52, 2006. [Full Text/Abstract]

Little JA, McGowan VR, Kato GJ, Partovi KS, Feld JJ, Maric I, Martyr S, Taylor JG 6th, Machado RF, Heller T, Castro O, Gladwin MT Combination erythropoietin-hydroxyurea therapy in sickle cell disease: experience from the National Institutes of Health and a literature review. Haematologica (91): 1076-83, 2006. [Full Text/Abstract]

Garcia-Eulate R, Hussain N, Heller T, Kleiner D, Malech H, Holland S, Choyke PL CT and MRI of hepatic abscess in patients with chronic granulomatous disease. AJR Am J Roentgenol (187): 482-90, 2006. [Full Text/Abstract]

O''Brien K, Hussain N, Warady BA, Kleiner DE, Kleta R, Bernardini I, Heller T, Gahl WA Nodular regenerative hyperplasia and severe portal hypertension in cystinosis. Clin Gastroenterol Hepatol (4): 387-94, 2006. [Full Text/Abstract]

Reshamwala PA, Kleiner DE, Heller T Nodular regenerative hyperplasia: not all nodules are created equal. Hepatology (44): 7-14, 2006. [Full Text/Abstract]

Perumalswami P, Kleiner DE, Lutchman G, Heller T, Borg B, Park Y, Liang TJ, Hoofnagle JH, Ghany MG Steatosis and progression of fibrosis in untreated patients with chronic hepatitis C infection. Hepatology (43): 780-7, 2006. [Full Text/Abstract]

Heller T, Rehermann B Acute hepatitis C: a multifaceted disease. Semin Liver Dis (25): 7-17, 2005. [Full Text/Abstract]

Heller T, Saito S, Auerbach J, Williams T, Moreen TR, Jazwinski A, Cruz B, Jeurkar N, Sapp R, Luo G, Liang TJ An in vitro model of hepatitis C virion production. Proc Natl Acad Sci U S A (102): 2579-83, 2005. [Full Text/Abstract]

Soza A, Heller T, Ghany M, Lutchman G, Jake Liang T, Germain J, Hsu HH, Park Y, Hoofnagle JH Pilot study of interferon gamma for chronic hepatitis C. J Hepatol (43): 67-71, 2005. [Full Text/Abstract]

Heller T, Seeff LB Viral load as a predictor of progression of chronic hepatitis C? Hepatology (42): 1261-3, 2005. [Full Text/Abstract]

Promrat K, Lutchman G, Uwaifo GI, Freedman RJ, Soza A, Heller T, Doo E, Ghany M, Premkumar A, Park Y, Liang TJ, Yanovski JA, Kleiner DE, Hoofnagle JH A pilot study of pioglitazone treatment for nonalcoholic steatohepatitis. Hepatology (39): 188-96, 2004. [Full Text/Abstract]

Rahman F, Heller T, Sobao Y, Mizukoshi E, Nascimbeni M, Alter H, Herrine S, Hoofnagle J, Liang TJ, Rehermann B Effects of antiviral therapy on the cellular immune response in acute hepatitis C. Hepatology (40): 87-97, 2004. [Full Text/Abstract]

Radaeva S, Jaruga B, Kim WH, Heller T, Liang TJ, Gao B Interferon-gamma inhibits interferon-alpha signalling in hepatic cells: evidence for the involvement of STAT1 induction and hyperexpression of STAT1 in chronic hepatitis C. Biochem J (379): 199-208, 2004. [Full Text/Abstract]

Liang TJ, Heller T Pathogenesis of hepatitis C-associated hepatocellular carcinoma. Gastroenterology (127): S62-71, 2004. [Full Text/Abstract]

Promrat K, McDermott DH, Gonzalez CM, Kleiner DE, Koziol DE, Lessie M, Merrell M, Soza A, Heller T, Ghany M, Park Y, Alter HJ, Hoofnagle JH, Murphy PM, Liang TJ Associations of chemokine system polymorphisms with clinical outcomes and treatment responses of chronic hepatitis C. Gastroenterology (124): 352-60, 2003. [Full Text/Abstract]

Heller T, Hoofnagle JH Denying the wolf access to sheep''s clothing. J Clin Invest (112): 319-21, 2003. [Full Text/Abstract]

Hoofnagle JH, Ghany MG, Kleiner DE, Doo E, Heller T, Promrat K, Ong J, Khokhar F, Soza A, Herion D, Park Y, Everhart JE, Liang TJ Maintenance therapy with ribavirin in patients with chronic hepatitis C who fail to respond to combination therapy with interferon alfa and ribavirin. Hepatology (38): 66-74, 2003. [Full Text/Abstract]

Triyatni M, Saunier B, Maruvada P, Davis AR, Ulianich L, Heller T, Patel A, Kohn LD, Liang TJ Interaction of hepatitis C virus-like particles and cells: a model system for studying viral binding and entry. J Virol (76): 9335-44, 2002. [Full Text/Abstract]

Soza A, Everhart JE, Ghany MG, Doo E, Heller T, Promrat K, Park Y, Liang TJ, Hoofnagle JH Neutropenia during combination therapy of interferon alfa and ribavirin for chronic hepatitis C. Hepatology (36): 1273-9, 2002. [Full Text/Abstract]

Sarkodee-Adoo C, Pittarelli L, Jaffe E, Sorbara L, Raffeld M, Yao X, Haddad R, Heller T Regression and clonally distinct recurrence of human immunodeficiency virus related Burkitt-like lymphoma during antiretroviral therapy. Leuk Lymphoma (42): 1125-31, 2001. [Full Text/Abstract]

Heller T, Drachenberg CB, Orens JB, Fantry GT Primary posttransplant lymphoproliferative disorder of the gallbladder in a lung transplant patient presenting with acute cholecystitis. Transplantation (69): 668-70, 2000. [Full Text/Abstract]

Darwin P, Zangara J, Heller T, Haluszka O, Laurin J Unsedated esophagoscopy for the diagnosis of esophageal varices in patients with cirrhosis. Endoscopy (32): 971-3, 2000. [Full Text/Abstract]

Heller T, James SP, Drachenberg C, Hernandez C, Darwin PE Treatment of severe esophageal Crohn''s disease with infliximab. Inflamm Bowel Dis (5): 279-82, 1999. [Full Text/Abstract]

Heller T, Yin S, Tsarev SA, Purcell RH, Emerson SU False-positive serologic test resulting from a probable yeast infection in a chimpanzee. Clin Diagn Lab Immunol (3): 614-5, 1996. [Full Text/Abstract]

Tobi M, Darmon E, Phillips T, Heller T, Rozen P, Nochomovitz L, Steinberg W Increased expression of a putative adenoma-associated antigen in pre-colonoscopic effluent of patients with colorectal cancer. Cancer Lett (51): 21-5, 1990. [Full Text/Abstract]



Clinical Protocols

  • Evaluation of the Immune Response in Humans After Exposure to Hepatitis C Virus , 00-DK-0221

  • Treatment of Chronic Delta Hepatitis with Pegylated Interferon, 01-DK-0247

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