Office: 457 Linus Pauling Science Center
Telephone: (541) 737-8018
Fax: (541) 737-0481
Email Address: firstname.lastname@example.org
Mailing/Express Delivery Address:
Adrian Gombart, Ph.D.
Linus Pauling Institute
Oregon State University
307 Linus Pauling Science Center
Corvallis, OR 97331
|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"|
Numerous health benefits have been attributed to vitamin D. Understanding the molecular mechanisms responsible for its many benefits is essential for understanding its importance as a nutritional supplement. We made the seminal discovery that vitamin D regulates the expression of a key antimicrobial protein (AMP) referred to as cathelicidin or CAMP/LL-37. Since the mid-19th century, sources of vitamin D such as sunlight and cod liver oil were routinely used to treat tuberculosis. Our findings identified an important component to understanding a key mechanism by which macrophages may combat Mycobacterium tuberculosis and other pathogens in humans.
Our studies revealed that regulation of CAMP by vitamin D was a human/primate-specific mechanism that was absent in mice and other mammals. To facilitate in vivo studies in an animal model, we developed a novel transgenic mouse carrying a human genomic fragment encoding the CAMP gene. This "humanized" mouse expresses the human CAMP gene in the expected tissues and is regulated by vitamin D. We will use this model to investigate the biological importance of the vitamin D pathway in maintaining a proper innate immune response toward invading pathogens, inflammation and our own microbiota. This model will provide an important experimental tool to understand the physiological importance of vitamin D in our diet and its impact on immune response.
The elderly are particularly susceptible to bone fractures, chronic inflammation and infectious diseases. They are also a group that is at high risk of suffering from vitamin D deficiency due to a combination of their reduced exposure to sunlight and the ability of their skin to produce it. As people age, the function of the adaptive and innate immune systems diminishes. As part of our research program, we are interested in investigating how vitamin D deficiency affects the innate immune system of the elderly and the potential of vitamin D supplementation to boost the innate immune response. Maintaining adequate function of the innate immune system, our front line defense, using micronutrients and vitamins may be critical in preventing microorganisms from gaining a foot hold and greatly improve the lifestyle of the elderly by reducing the rates or severity of infections.
The studies underway in my lab, utilize a combination of molecular and cellular biological approaches involving tissue culture and animal models to elucidate the biological and physiological importance of vitamin D in maintaining a healthy innate immune response. Immediate projects are focused on 1) understanding the transcriptional regulation of the CAMP gene with the goal of identifying additional pathways that may be regulated by nutritional factors; 2) identifying additional nutrients that regulate the CAMP gene; 3) utilizing the mouse model to elucidate the molecular mechanisms for vitamin D's ability to provide protection against infection and 4) elucidating the role of this pathway in the immune response of the elderly and identifying ways that supplementation may improve their immune response to infection.
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, 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, Rossi JJ. (2012) Interplay between HIV-1 infection and host microRNAs. Nucleic Acids Res 40:2181-2196.