Office: 457 Linus Pauling Science Center
Telephone: (541) 737-8018
Fax: (541) 737-5077
Email Address: email@example.com
Mailing/Express Delivery Address:
Adrian Gombart, Ph.D.
Linus Pauling Institute
Oregon State University
307 Linus Pauling Science Center
Corvallis, OR 97331
Our research is focused on understanding the regulation of antimicrobial peptide expression by the vitamin D pathway. When immune cells called macrophages encounter a pathogen and become activated, the vitamin D pathway is turned on, leading to the induction of the cathelicidin antimicrobial peptide if serum levels of vitamin D are sufficient. We have shown that this mechanism is conserved in humans and primates but not in other mammals. Therefore, we developed a transgenic mouse that carries the human cathelicidin gene. Using this model, we are testing the ability of vitamin D to protect against infection by influenza, Salmonella, and Mycobacterium tuberculosis. Vitamin D has been used to treat tuberculosis, and its deficiency is associated with increased risk of tuberculosis. This model will allow us to test the role of vitamin D and cathelicidin during initial infection, latency, and reactivation.
Another focus of our research is to identify additional dietary compounds that regulate the expression of the cathelicidin gene. This gene is also induced by sodium butyrate and lithocholic acid, which functions through the vitamin D receptor. Nutrients that bind the vitamin D receptor may modulate the immune system by inducing the cathelicidin gene. We discovered that curcumin in curry modestly induces expression of the cathelicidin gene, which could protect the gut from infection. In collaboration with colleagues at Cedars-Sinai Medical Center, we discovered that vitamin B3 (niacin) boosts killing of methicillin-resistant Staphylococcus aureus (MRSA) by white blood cells, in part, by increasing cathelicidin levels. A small molecule library is being screened for regulators of the cathelicidin gene. The identification of new regulatory compounds may give clues as to how the gene is regulated in vivo and lead to the identification of other nutrients that can be used to boost the immune system.
Finally, we are interested in determining the effect of vitamin D on the function of the innate immune system in the elderly. Aging is accompanied by low-grade, chronic, systemic inflammation, and vitamin D has important anti-inflammatory properties. We want to determine if sufficient levels of vitamin D will reduce the inflammatory phenotype. We also want to determine if reversing severe deficiency will raise cathelicidin protein levels in the blood, which may reduce mortality in kidney dialysis and sepsis patients.
|1986||B.S., Biology, Oregon State University, Corvallis, OR|
|1989||M.S., Genetics, Oregon State University, Corvallis, OR|
|1994||Ph.D., Microbiology, University of Washington, Seattle, WA|
|1993-1997||Post-doctoral Fellow, Division of Hematology/Oncology, David Geffen School of Medicine at UCLA, Cedars-Sinai Medical Center|
|1997-2006||Research Scientist, Division of Hematology/Oncology, Cedars-Sinai Medical Center; Adjunct Assistant Professor, Department of Medicine, David Geffen School of Medicine at UCLA|
|2006-2008||Research Scientist, Division of Hematology/Oncology, Cedars-Sinai Medical Center; Adjunct Associate Professor, Department of Medicine, David Geffen School of Medicine at UCLA|
|2008-present||Principal Investigator, Linus Pauling Institute,
Oregon State University
Associate Professor, Department of Biochemistry and Biophysics, Oregon State University
American Society of Hematology
Society for Leukocyte Biology
The Science Advisory Board
|2007-2012||Research Grant, NIAID/NIH, "Regulating Cathelicidin Expression for Disease Therapy"|
Gombart AF, Bhan I, Borregaard N, Tamez H, Camargo Jr CA, Koeffler HP, and Thadhani R. (2009) Low plasma level of cathelicidin antimicrobial peptide (hCAP18) predicts increased infectious disease mortality in patients undergoing hemodialysis. Clin Infect Dis 48:418-424.
Adams JS, Ren S, Liu PT, Chun RF, Lagishetty V, Gombart AF, Borregaard N, Modlin RL, and Hewison M. (2009) Vitamin D-directed rheostatic regulation of monocyte antibacterial responses. J Immunol 182:4289-4295.
Gombart AF, Saito T, and Koeffler HP. (2009) Exaptation of an ancient Alu short interspersed element provides a highly conserved vitamin D-mediated innate immune response in humans and primates. BMC Genomics 10:321.
Uh A, Simmons CF, Bresee C, Khoury N, Gombart AF, Nicholson RC, Kocak H, and Equils O. (2009) MyD88 and TRIF mediate the cyclic adenosine monophosphate (cAMP) induced corticotropin releasing hormone (CRH) expression in JEG3 choriocarcinoma cell line. Reprod Biol Endocrinol 7:74.
Gombart AF. (2009) The vitamin D-antimicrobial peptide pathway and its role in protection against infection. Future Microbiol 4:1151-1165.
Akagi T, Thoennissen NH, George A, Crooks G, Song JH, Okamoto R, Nowak D, Gombart AF, and Koeffler HP. (2010) In vivo deficiency of both C/EBPβ and C/EBPε results in highly defective myeloid differentiation and lack of cytokine response. PLoS One 5:e15419.
Sun G, Li H, Wu X, Covarrubias M, Scherer L, Meinking K, Luk B, Chomchan P, Alluin J, Gombart AF, and Rossi JJ. (2012) Interplay between HIV-1 infection and host microRNAs. Nucleic Acids Res 40:2181-2196.
Dixon BM, Barker T, McKinnon T, Cuomo J, Frei B, Borregaard N, and Gombart AF. (2012) Positive correlation between circulating cathelicidin antimicrobial peptide (hCAP18/LL-37) and 25-hydroxyvitamin D levels in healthy adults. BMC Res Notes 5:575.
Kyme P, Thoennissen NH, Tseng CW, Thoennissen GB, Wolf AJ, Shimada K, Krug UO, Lee K, Müller-Tidow C, Berdel WE, Hardy WD, Gombart AF, Koeffler HP, and Liu GY. (2012) C/EBPε mediates nicotinamide-enhanced clearance of Staphylococcus aureus in mice. J Clin Invest 122:3316-3329.
Campbell Y, Fantacone ML, and Gombart AF. (2012) Regulation of antimicrobial peptide gene expression by nutrients and by-products of microbial metabolism. Eur J Nutr 51:899-907.
Guo C, Rosoha E, Lowry MB, Borregaard N, and Gombart AF. (2013) Curcumin induces human cathelicidin antimicrobial peptide gene expression through a vitamin D receptor-independent pathway. J Nutr Biochem 24:754-759.