Brian VanderVen, PhD
M. tuberculosis causes human tuberculosis and is responsible for approximately one-million deaths each year. Partly why M. tuberculosis is such a successful pathogen is that this bacterium can survive inside macrophages, an immune cell that kills most other bacteria. Additionally, M. tuberculosis infections typically persist in human beings for decades in the face of a functional immune response.
The laboratory is focused on understanding how M. tuberculosis survives and maintains infections in mammals. The goals of my research program are to: (1) understand how M. tuberculosis acquires and utilizes nutrients during acute and chronic phases of disease and, (2) apply this understanding to discover new anti-TB drugs. We use chemical-genetics, genomics, and biochemical approaches to discover and characterize the novel M. tuberculosis proteins and pathways required during infection. These findings are also used in conjunction with high-throughput drug discovery approaches to identify small molecules that inhibit these same proteins or pathways. The overarching goals of the lab are to better understand the basic biology of tuberculosis infections and discover new drugs for treatment.
PhD (Colorado State University)
Dr. VanderVen, an Assistant Professor in the Department of Microbiology and Immunology, received his Bachelor of Science from Montana State University and his PhD from Colorado State University. While a postdoctoral fellow he has began his research on understanding mycobacterial physiology during intracellular infection.
Immunometabolism at the interface between macrophages and pathogens. Russell DG, Huang L, and VanderVen BC. 2019 Nature Reviews Immunology accepted
The genetic requirements of fatty acid import by Mycobacterium tuberculosis within macrophages. Nazarova EV, Montague CR, Huang L, La T, Russell DG, and VanderVen BC. 2019 eLife accepted.
Cholesterol and fatty acids grease the wheels of Mycobacterium tuberculosis pathogenesis. Wilburn KM, Fieweger RA, VanderVen BC. Pathog Dis. 2018 Mar 1;76(2). doi: 10.1093/femspd/fty021.
Nazarova E, Podinovskaia M, Russell DG, and VanderVen BC. Flow Cytometric Quantification of Fatty Acid Uptake by Mycobacterium tuberculosis in Macrophages. Bio-protocols. 2018 (8)4.
Clark MP, Wang T, Perola E, Deininger DD, Zuccola HJ, Jones SM, Gao H, VanderVen BC, Russell DG, Shoen CM, Cynamon MH, Thomson JA, Locher CP. 2-N-Arylthiazole inhibitors of Mycobacterium tuberculosis. Bioorg Med Chem Lett. 2017 Sep 1;27(17):3987-3991.
Nazarova E, Montague CR, La T, Wilburn KM, Lee W, Sukumar N, Caldwell S, Russell DG, and VanderVen BC. Rv3723/LucA coordinates fatty acid and cholesterol uptake in Mycobacterium tuberculosis. eLife. 2017. (6) pii: e26969.
Tuohetahuntila M, Molenaar MR, Spee B, Brouwers JF, Wubbolts R, Houweling M, Yan C, Du H, VanderVen BC, Vaandrager AB, Helms JB. Lysosome-mediated degradation of a distinct pool of lipid droplets during hepatic stellate cell activation. J Biol Chem. 2017 Jul 28;292(30):12436-12448.
Johnson RM, Bai G, DeMott CM, Banavali NK, Montague CR, Moon C, Shekhtman A, VanderVen BC*, McDonough KA. Chemical activation of adenylyl cyclase Rv1625c inhibits growth of Mycobacterium tuberculosis on cholesterol and modulates intramacrophage signaling. Mol Microbiol. 2017 Jul;105(2):294-308. *co-corresponding author
Lee W, VanderVen BC, Walker S, Russell DG. . 2017 Novel protein acetyltransferase, Rv2170, modulates carbon and energy metabolism in Mycobacterium tuberculosisScience Reports. Dec 7(1)72.
VanderVen BC, Huang L, Rohde K, and Russell DG. 2016. The minimal unit of infection: Mtb in the macrophage. Microbiol Spectr. Dec 4(6).
Liu Y, Tan S, Huang L, Abramovitch RB, Rohde K, Zimmerman Z, Chen C, Dartois V, VanderVen BC, and Russell DG. 2016 Immune activation of the host cell induces drug tolerance in Mycobacterium tuberculosis both in vitro and in vivo. J Experimental Medicine. May 2;213(5):809-25.
Lovewell RR, Sassetti CM, VanderVen BC. 2016. Chewing the fat: lipid metabolism and homeostasis during M. tuberculosis infection. Curr Opin Microbiol. Feb 29:30-6.
VanderVen BC, Fahey RJ, Lee W, Liu Y, Abramovitch RB, Memmott C, Crowe AM, Eltis LD, Perola E, Deininger DD, Wang T, Locher CP, Russell DG. 2015. Novel inhibitors of cholesterol degradation in Mycobacterium tuberculosis reveal how the bacterium’s metabolism is constrained by the intracellular environment. Plos Pathogens, Feb 12 (11)2.
Russell DG, Lee W, Tan S, Sukumar N, Podinovskaia M, Fahey RJ, VanderVen BC. The Sculpting of the Mycobacterium tuberculosis Genome by Host Cell-Derived Pressures. Microbiol Spectr. 2014;2(2).
Podinovskaia M, VanderVen BC, Yates RM, Glennie S, Fullerton D, Mwandumba HC, and Russell DG. 2013. Dynamic quantitative assays of phagosomal function. Current Protocols Immunology, 102:14-34.
Lee W, VanderVen BC, and Russell, DG. 2013. Intracellular Mycobacterium tuberculosis exploits host-derived fatty acids to limit metabolic stress. J Biol Chem, 288(10):6788-6800.
Thomas ST, VanderVen BC*, Sherman DR, Russell DG, and Sampson NS. 2011. Pathway Profiling in Mycobacterium tuberculosis: Elucidation of a Cholesterol-derived Catabolite and the Enzymes that Catalyze its Metabolism. J Biol Chem, 286(51):43668-43678.*co-first author and co-corresponding author.
Mann, FM, VanderVen BC, and Peters RJ. 2011. Magnesium depletion triggers production of an immune modulating diterpenoid in Mycobacterium tuberculosis. Molecular Microbiology, 79(6):1594-15601.
Russell DG, VanderVen BC, et al. 2010. Mycobacterium tuberculosis wears what it eats. Cell Host Microbe, 8(1):68-76.
VanderVen BC, et al. 2010. Exploitation of a cell-based, chemical screen to identify inhibitors of phagosomal lipolysis. Cytometry Part A, 77A(8):751-760.
Russell DG, VanderVen BC, et al. 2009. The macrophage marches on its phagosome: Dynamic assays of phagosomal function. Nature Reviews in Immunology, 9(8):594-600.
VanderVen BC*, Yates RM, and Russell DG. 2009. Intraphagosomal measurement of the magnitude and duration of the oxidative burst. Traffic, 10(4):372-378. *corresponding author
Van de Walle GR, Peters ST, VanderVen BC, O’Callaghan DJ, and Osterrieder N. 2008. Equine herpesvirus type 1 (EHV-1) entry via endocytosis is facilitated by α-V integrins and an RSD motif in glycoprotein D. Journal of Virology, 82(23):11859-11868.
Owens RM, Hsu FF, VanderVen BC, et al. 2006. M. tuberculosis Rv2252 encodes a diacylglycerol kinase involved in the biosynthesis of phosphatidylinositol mannosides (PIMs). Molecular Microbiology, 60(5):1152-1163.
VanderVen BC, Harder JD, Crick DC, and Belisle JT. 2005. Export-mediated assembly of mycobacterial glycoproteins parallels eukaryotic pathways. Science, 309(5736):941-943.
Awards and Honors