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KU Home  :  Pharmaceutical Chemistry  :  Pharmaceutical Chemistry - Faculty - Jeff Krise Ph.D.
Jeff Krise Ph.D
Associate Professor, Director of Graduate Studies
Departments: Pharmaceutical Chemistry
Office: 236B Simons Labs
Email: Krise@ku.edu
Phone: (785) 864-2626
Fax: (785) 864-5736

Educational Background:

1993, BS in Pharmacy, Duquesne University
1998, PhD in Pharmaceutical Chemistry, The University of Kansas
1998-2001, Postdoctoral Research, Dept. of Biochemistry, Stanford University

Research Group:

  • Ryan Funk: Graduate Student
  • Stephen Goldman: Graduate Student
  • Shan Huang: Graduate Student
  • Randall Logan: Graduate Student
  • Rosemary Ndolo: Graduate Student

Research Interests:

Research in the Krise laboratory is focused on understanding driving forces important in the transport and/or distribution of drugs and endogenous small molecular weight molecules within the array of intracellular compartments contained within mammalian cells.

The laboratory approaches this research objective from two separate directions. One is biochemical in orientation and includes the identification of proteins, pH and electrochemical gradients that are associated with specific intracellular compartments that play a role in transport and distribution. The second approach is more chemical in nature and attempts to correlate physicochemical properties of molecules with intracellular localization. These approaches offer a synergistic means to improve our fundamental understanding of intracellular transport and distribution phenomena.

The therapeutic applications of this research are currently focused in two separate areas. One is focused on improving the intracellular distribution of drugs to favor interactions with intended targets and to avoid distribution to sites not containing them, as to lessen the potential for side effects. The laboratory has shown that it is possible to design/select drugs that distribute differently in different types of cells (i.e., normal versus cancer), which has led to the creation of a novel platform for improving the selectivity of anticancer agents towards tumor cells.

The second area involves the study of proteins that are directly or indirectly involved in maintaining normal intracellular distribution of endogenous small molecular weight compounds in patients with neurodegenerative disorders such as Niemann-Pick Type C disease. Cells are continuously exposed to numerous endogenous small molecular weight molecules (i.e., neurotransmitters, polyamines, steroids, etc.) that normally localize within discreet subcellular locations at defined concentrations. The laboratory is currently evaluating two late endosomal/lysosomal proteins named Niemann-Pick C1 and Niemann-Pick C2 that are believed to play an important role in regulating the retrograde transport of multiple lysosomal cargos, which we have recently shown to include endogenous amines.

Current Research Projects:

Publications:

Representative publications:

Kaufmann, A. M., Goldman, S. D. B., & Krise, J. P. (2009) A fluorescence resonance energy transfer-based approach for investigating late endosome-lysosome retrograde fusion events. Anal Biochem. 386, 97-97.

Kaufmann, A.M. and Krise, J.P. (2008) Niemann-Pick C1 functions in regulating lysosomal amine content. J. Biol. Chem. 283, 24584-24593.

Kaufmann, A.M., Toro-Ramos, A.J. and Krise, J.P. (2008) Assessment of Golgi apparatus versus plasma membrane-localized multi-drug resistance-associated protein 1. Mol Pharm. 5, 787-794.

Gong, Y., Zhao, Z., McConn, D.J., Beaudet, B., Tallman, M., Speake, J.D., Ignar, D.M., and Krise, J.P. (2007) Lysosomes contribute to anomalous pharmacokinetic behavior of melanocortin-4 receptor agonists. Pharm Res. 24 1138-1144.

Duvvuri, M., Konkar, S.V., Hong, K.H., Blagg, B.S.J. and Krise, J.P. (2006) A new approach for enhancing differential selectivity of drugs to cancer cells. ACS Chem. Biol. 1, 309-305.

Gong, Y., Duvvuri, M., Duncan, M.B., Liu, J. and Krise, J.P. (2006) Niemann-Pick C1 protein facilitates the efflux of the anticancer drug daunorubicin from cells according to a novel vesicle-mediated pathway. J. Pharmacol. Exp. Ther. 316, 242-247.

Duvvuri, M., Konkar, S.V., Funk, R.S., Krise, J.M and Krise, J.P. (2005) A chemical strategy to manipulate the intracellular localization of drugs in a multi-drug resistant cancer cell line. Biochemistry, 44, 15743-15749.

Duvvuri, M. and Krise J.P. (2005) A novel assay reveals that weakly basic model compounds concentrate in lysosomes to an extent greater than pH-partitioning theory would predict. Mol. Pharm. 2, 440-448.

Duvvuri, M., Gong, Y., Chatterji, D. and Krise, J.P. (2004) Weak base permeability characteristics influence the intracellular sequestration site in the multidrug-resistant human leukemic cell line HL-60. J. Biol. Chem. 279, 32367-32372.

Gong, Y., Duvvuri, M., and Krise, J.P. (2003) Separate roles for the Golgi apparatus and lysosomes in the sequestration of drugs in the multi-drug resistant human leukemic cell line HL-60. J. Biol. Chem. 278, 50234-50239.

Carroll, K.S, Hanna, J., Simon, I., Krise. J.P., Barbero, P. and Pfeffer, S.R. (2001) Role of Rab9 GTPase in facilitating receptor recruitment by TIP47. Science. 292, 1373-1376.

Krise, J.P., Orsel, J.G., Sincock, P.M. and Pfeffer, S.R. (2000) Quantitative analysis of TIP47-receptor cytoplasmic domain interactions: implications for endosome-to-trans Golgi network trafficking. J. Biol. Chem. 275, 25188-25193.