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Research Interests
Dr. Howell’s clinical interests include management of chronic liver diseases, particularly hepatitis B and C, primary biliary cirrhosis and autoimmune hepatitis. He has 3 main research interests: 1) understanding the pathogenesis of liver injury due to chronic hepatitis C, 2) studying host genes and cellular pathways that mediate HCV clearance spontaneously and during interferon and ribavirin therapy; and 3) racial disparities in hepatitis C and primary hepatocellular carcinoma.
Dr. Howell was chair of the Steering Committee and principal investigator for the Baltimore site of the NIDDK Study of Viral Resistance to Antiviral Therapy for Chronic Hepatitis C (VIRAHEP-C) (2001-2006). In addition, he is a recipient of a RO1 award (2004-2007) titled “Predicting the Outcomes of Hepatitis C Treatments”. Using gene microarray technology, this project is testing the hypothesis that differential expression of host immune and inflammatory genes in the livers of African American and Caucasian HCV patients prior to treatment might be responsible for the racial disparity in treatment outcomes. If so, measuring the global patterns of gene expression in liver biopsies obtained prior to treatment might be predict the efficacy of antiviral therapy for chronic HCV in genotype 1. The results should provide new insights into the basis for the racial differences in the sensitivity and resistance to antiviral therapy, and facilitate development of more effective treatments for HCV genotype 1.
In 2005, Dr. Howell received a NIH mid-career investigator inpatient-oriented research (K24) award. The longterm objective of the award is to decrease racial disparities in liver diseases in the United States by conducting well-designed patient-oriented research and by increasing the number of highly trained research scientist engaged in patient-oriented research in digestive diseases. A better understanding of the causes for health disparities based on race is necessary to develop comprehensive strategies to improve the health of racial minorities in the US. The award provides protected time for Dr. Howell to engage in clinical research; to mentor trainees interested in patient-oriented liver research at the University of Maryland; and to strengthen his background for future patient-oriented research projects and mentoring by completing didactic coursework in clinical investigation; and to conduct preliminary studies on racial disparities in primary hepatocellular carcinoma (HCC) in the US.
Publications
Luo, S., Cassidy W, Jeffers LS, Reddy KR, Bruno C, Howell, CD. Interferon-stimulated gene expression in Black American and White HCV patients during peginterferon alfa-2a combination therapy. Clinical Gastroenterology and Hepatology 2004; 3 (5): 499-506. 2005.
Yu L, Sloane D, Guo C, Howell, CD. Characteristics and outcomes of African American patients with Hepatocellular Carcinoma: findings from the nationwide inpatient sample. Clinical Gastroenterology and Hepatology 2006; 4(3): 355-360.Howell, CD, Jeffers, LS, Cassidy W, Reddy, KR, Hu, S. Peginterferon alfa-2a and ribavirin for chronic hepatitis C genotype 1 Infection in Black patients: Safety, tolerability and impact on sustained virologic response. Journal of Viral Hepatitis 2006; 13: 371-376.
Conjeevaram, HS, Fried, MW, Jeffers, LJ, Terrault, N, Wiley, TE, Afdhal, N, Brown, RS, Belle, SH, Hoofnagle, JH, Kleiner, DE, #Howell, CD. Peginterferon and ribavirin treatment in african american and caucasian american patients with chronic hepatitis C genotype 1. Gastroenterology 2006, 31(2): 470-7.
Sloane, D, Chen H, #Howell, CD. Racial Disparity in Primary Hepatocellular carcinoma: Tumor stage at presentation, surgical treatment, and survival. J Natl Med Assoc. 2006, 98(12):1934-9.
Huang Y, Yang H, Borg B.B., Su X. Rhodes S.L., Yang K., Tong X., Tang G., Howell C.D., Rosen H.R., Thio C., Thomas D.L., Alter H.A. Jr., Sapp T., Liang T.J. A novel functional single nucleotide polymorphism of interferon-g gene is important for interferon-a-induced and spontaneous recovery from HCV infection. Proc Natl Acad Sci U S A. 2007 Jan 16; 104(3): 985-90.
Taylor, M Tuatara, T, Brodsky, L., Schaley, J., Sanda, C., Stephens, M.J., McClintick, J.N., Edenberg, H.J., Li, L., Tavis, J.E., Howell, C, Belle, S.H. Changes in gene expression during peginterferon and ribavirin therapy of chronic hepatitis C distinguish responders from nonresponders to antiviral therapy. Journal of Virology, 2007, 81(7): 3391-4001.
Howell CD, Dowling T, Paul M, Wahed AS, Terrault NA, Taylor M, Jeffers L, Hoofnagle JH. Peginterferon Pharmacokinetics in African American and Caucasian American Patients with Hepatitis C Virus Genotype 1 Infection. Clinical Gastroenterology and Hepatology, 2008, 6(5): 575-83.
Su X, Yee LJ, Im KA, Rhodes SL, Tang YM, Tong X, Howell C, Ramcharran D, Rosen HR, Taylor MW, Liang TJ, Yang H. Association of single nucleotide polymorphisms in interferon signaling pathway genes and interferon stimulated genes with the response to interferon therapy for chronic hepatitis C. Journal of Hepatology, 2008; 49(2): 184-89.
Huang C, Cassidy W, Chen H, Howell CD. Peripheral blood gene expression profiles predict sustained virologic response following peginterferon and ribavirin therapy. J Natl Med Assoc. 2008, 100(12): 1025-1433.
Feyssa EL, Philosophe B, Howell, CD. Analysis of variables responsible for the racial disparity in kidney transplantation outcomes. J Natl Med Assoc. 2009; 101(2): 111- 115. PMID: 19378626
Hoofnagle JH, Wahed AS, Brown, RS Jr., Howell CD, Belle SH. Early Changes in hepatitis C viral levels in response to peginterferon and ribavirin in patients with chronic hepatitis C genotype 1 Infection. Journal of Infectious Diseases. 2009; 199(8): 1112-1120. PMID: 19284286
Howell, CD. Editorial: Racial disparities in liver transplantation for hepatitis B: To be or not to be. Liver Transplantation, 2009, 15(9) 1007-1009. PMID: 19718630
Liu Z, Gartenhaus, R.B., Chen, X.W., Howell, C.D., Tan, M. Survival prediction and gene identification with penalized global AUC maximization. J. Comput Biol, 2009. PMID: 19772397