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Focco van den Akker, PhD

Associate Professor
Department of Biochemistry
School of Medicine

Research Information

Research Interests

The van den Akker lab carries out structure-function and inhibitor design studies to combat antibiotic resistance. We study known drug targets and also aim to discover new Achilles' heel opportunities: the main targets are proteins involved in peptidoglycan metabolism including penicillin-binding proteins (PBPs), beta-lactamases, and lytic transglycosylases among others. We explore mechanism-based reaction-coordinate inhibitors and also employ fragment-based ligand discovery approaches. Key techniques used are protein crystallography, biophysical tools to probe ligand binding (DSF and SPR), computational methods (in silico docking and molecular dynamics simulations), and enzymatic assays while collaborating with expert microbiologists, biochemists, medicinal chemists, and pharmaceutical companies.

Additional non-antibiotic resistance drug-discovery related projects include developing and studying new agents to prevent pre-term birth (NIH funded collaboration with Dr. Sam Mesiano) and developing nitrosylation modulators (NIH funded collaboration with Dr. Jonathan Stamler).

Research Projects

van den Akker 

Publications

Publication Date

  • Alsenani, T.A., Viviani, S.L., Papp-Wallace, K.M., Bonomo, R.A., van den Akker, F. (2023) Antimicrob Agents Chemother. e0035023.
  • Kumar, V., Boorman, J., Greenlee, W.J., Zeng, X., Lin, J., van den Akker, F. (2023) Protein Sci. e4683.
  • Zhou, H.L., Hausladen, A.A., Anand, P., Rajavel, M., Stomberski, C.T., Zhang, R., Premont, R.T., Greenlee, W.J., van den Akker, F., Stamler, J.S. 2023) J. Med. Chem. 66(8):5657-5668.
  • Alsenani, T.A., Viviani, S.L., Kumar, V., Taracila, M.A., Bethel, C.R., Barnes, M.D., Papp-Wallace, K.M., Shields, R.K., Nguyen, M.H., Clancy, C.J., Bonomo, R.A., van den Akker, F. (2022) Antimicrob Agents Chemother. E0241421.
  • Taracila, M.A., Bethel, C.R., Hujer, A.M., Papp-Wallace, K.M., Barnes, M.D., Rutter, J.D., VanPelt, J., Shurina, B.A., van den Akker, F., Clancy, C.J., Nguyen, M.H., Cheng, S., Shields, R.K., Page, R.C., and Bonomo, R.A. (2022)   Antimicrob Agents Chemother. E0212421.
  • Kumar, V., Viviani, S.L., Ismail, J., Agarwal, S., Bonomo, R.A., van den Akker, F. (2021) PLoS One 2021 16(10): e0258359.
  • Goldberg, J., Kumar, V., Spencer, E., Hoyer, D., Marshall, S., Hujer, A., Hujer, K., Bethel, C., Papp-Wallace, K.M., Perez, F., Jacobs, M., van Duin, D., Kreiswirth, B., van den Akker, F.*, Plummer, M.*, Bonomo, R.A.* (2021) Eur. J. Med. Chem. 220, 113436.
  • Kumar, V., Mathure, S.A., Lee, M., Boorman, J., Zeng, X., Lin, J., Hesek, D., Mobashery, S., van den Akker, F. (2021) Biochemistry, 60, 1133-1144.
  • Hahn, M.G., Lampe, T., Sheikh, S. Griebenow, N., Woltering, E., Schlemmer, K.-H., Dietz, L., Gerisch, M., Wunder, F., Becker-Pelster, E.-M., Modritzki, T., Tinel, H., Knorr, A., Kern, A., Lang, D., Hüser, J., Schomber, T., Benardeau, A., Eitner, F., Trübel, H., Mittendorf, J., Kumar, V., van den Akker, F., Schaefer, M., Geiss, V., Sandner, P., Stasch, J.-H., (2021) "" (BAY 1101042). J. Med. Chem. 64, 5323-5344.
  • Rajavel, M., Kumar, V., Nguyen, H., Wyatt, J., Marshall, S. H., Papp-Wallace, K. M., Deshpande, P., Bhavsar, S., Yeole, R., Bhagwat, S., Patel, M., Bonomo, R. A., and van den Akker, F. (2021)

    mBio 12, e03058-03020.
  • Goldberg, J.A., Nguyen, A., Kumar, V., Spencer, E.J., Hoyer, D., Marschall, E.K., Cmolik, A., O'Shea, M., Marshall, S.H., Hujer, A.M., Hujer, K.M., Rudin, S.D., Domitrovic, N., Bethel, C.R., Papp-Wallace, K.M., Logan, L.K., Perez, F., Jacobs, M.R., van Duin, D., Kreiswirth, B.M., Bonomo, R.A.*, Plummer, M.S.*, van den Akker F.* (2020), 
    J. Med. Chem. 63, 5990-6002.
  • Kumar, V., Tang, C., Bethel C.R., Papp-Wallace K.M., Wyatt, J., Desarbre, E., Bonomo, R.A., van den Akker F. . Antimicrob Agents Chemother.
  • Papp-Wallace, K.M.*, Kumar, V., Zeiser, E.T., Becka, S.A., van den Akker F. * (2019) . Antibiotics (Basel). 8, pii: E145. 
  • Mesiano, S.A., Peters, G.A., Amini, P., Wilson, R.A., Tochtrop, G.P., van den Akker. F. (2019) . Placenta 79, 46-42. 
  • Barnes, M.D., Kumar, V., Bethel, C.R., Moussa, S.H., O’Donnell, J., Rutter, J.D., Good, C.E., Hujer, K.M., Hujer, A.M., Marshall, S.H., Kreiswirth, B.N., Richter, S.S., Rather, P.N., Jacobs, M.R., Papp-Wallace, K.M., van den Akker, F.*, Bonomo, R.A.* (2019) . mBio, e00159-19. *co-corresponding authors 
  • Stomberski, C.T., Zhou, H.-L., Wang, L., van den Akker, F., Stamler, J.S. (2018) . J. Biol. Chem. 294, 1568-1578.
  • Vijayaraghavan, J., Kumar, V., Krishnan, N.P., Kaufhold, R.T., Zeng, X., Lin, J., van den Akker, F.
    “ ”
    Plos One 2018, e0197136. 
  • Papp-Wallace, K.M.*, Nguyen, N.Q., Jacobs, M.R., Bethel, C.R., Barnes, M.D., Kumar, V., Bajaksouzian, S., Rudin, S.D., Bhavsar, S., Ravikumar, T., Deshpande, P.K., Patil, V., Yeole, R., Bhagwat, S.S., Patel, M.V., van den Akker, F.*, Bonomo, R.A.*

    J. Med. Chem 2018, 61, 4067-4086.
  • van den Akker, F.*, Bonomo, R.A.

    Front Microbiol. 2018, 9, 622. 
  • Chen A., Tiosano, D., Guran, T., Baris, H.N., Bayram, Y., Mory, A., Shapiro-Kulnane, L., Hodges, C.A., Coban Akdemir, Z., Turan, S., Jhangiani, S.N., van den Akker, F., Hoppel, C.L., Salz, H.K., Lupski, J.R., Buchner, D.A.

    Hum Mol. Genet. 2018, 27, 1913-1926. 
  • Nguyen N.Q., Krishnan N.P., Rojas L.J., Prati F., Caselli E., Romagnoli C., Bonomo R.A., van den Akker F.

    Antimicrob Agents Chemother. 2016, 60, 1760-6. 
  • Krishnan N.P., Nguyen N.Q., Papp-Wallace K.M., Bonomo R.A., van den Akker F.

    Plos One Sep 4;10(9):e0136813 (2015) 
  • Rodkey E.A., Winkler, M.L., Bethel C.R., Pagadala, S.R.R., Buynak, J.D., Bonomo R.A., van den Akker F.

    Plos One Jan 16;9(1):e85892 (2014) 
  • Rodkey E.A., McLeod D.C., Bethel C.R., Smith K.M., Xu Y., Chai W., Che T., Carey P.R., Bonomo R.A., van den Akker F., Buynak J.D.

    J. Am. Chem. Soc. Epub Dec 3(2013) 
  • von Wantoch Rekowski M., Kumar V., Zhou Z., Moschner J., Marazioti A., Bantzi M., Spyroulias G.A., van den Akker F., Giannis A., Papapetropoulos A.

    J. Med. Chem. Epub Oct 24(2013) 
  • Kumar V., Martin F.E., Hahn M.G., Schaefer M., Stamler J.S., Stasch J.P., van den Akker F.

    Biochemistry Epub Apr 24 (2013) 
  • Ke W., Pattanaik P., Bethel C.R., Sheri A., Buynak J.D., Bonomo R.A., van den Akker F.

    Plos One e49035 (2012) 
  • Rodkey E.A., Drawz S.M., Sampson J.M. Bethel C.R., Bonomo R.A., and van den Akker F.

    J. Am. Chem. Soc. epub Sep 26, (2012) 
  • Ke W., Laurent A.H., Armstrong M.D., Chen Y., Smith W.E., Liang J., Wright C.M., Ostermeier M., and van den Akker, F. 
    Plos One 7: e39168 (2012) 
  • Ke W, Rodkey R.A., Sampson J.M., Skalweit M.J., Sheri A., Pagadala S.R.R., Nottingham M.D., Buynak J.D., Bonomo R.A., van den Akker F.

    ChemMedChem 7: 1002-1008 (2012) 
  • Ke W., Bethel C.R., Papp-Wallace K.M., Pagadala S.R., Nottingham M., Fernandez D., Buynak J.D., Bonomo R.A., van den Akker F.

    Antimicrob Agents Chemother ePub Feb 13 (2012) 
  • Sampson J. M., Ke, W., Bethel, C. R., Pagadala, S. R. R., Nottingham, M. D., Bonomo R. A., Buynak, J. D., and van den Akker F.

    Antimicrob Agents Chemother 55 (1): 2303-2309 (2011). 
  • Ke W., Sampson J. M., Ori C., Prati F., Drawz S. M., Bethel C. R., Bonomo R. A., and van den Akker F.

    Antimicrob Agents Chemother 55 (1): 174-83 (2011). 
  • Ma X., Beuve A., and van den Akker F.

    BMC Struct Biol 10: 2 (2010). 
  • Martin F., Baskaran P., Ma X., Dunten P. W., Schaefer M., Stasch J. P., Beuve A., and van den Akker F.

    J Biol Chem 285 (29): 22651-7 (2010). 
  • Ma X., Sayed N., Baskaran P., Beuve A., and van den Akker F.

    J Biol Chem 283 (2): 1167-78 (2008). 
  • Ma X., Sayed N., Beuve A., and van den Akker F.

    EMBO J 26 (2): 578-88 (2007). 
  • Sayed N., Baskaran P., Ma X., van den Akker F., and Beuve A.

    Proc Natl Acad Sci U S A 104 (30): 12312-7 (2007). 

Education

PhD
University of Washington
Post Doc
Lerner Research Institute, Cleveland Clinic