Department of Molecular Medicine

Osmulski Pawel  A. OsmulskiPh.D.

Assistant Professor/Research

Profile and Contact Information | Research



Research Program

My leading specialties are biophysics and structural biology. I have more than 25 years of experience with studying protein-protein and protein-small ligand interactions with biological chemistry, biochemical and biophysical methods. I mastered spectroscopic methods for protein studies as a postdoctoral fellow in the laboratories of Drs. Debrunner and Hager at the University of Illinois at Urbana-Champaign. Then, I was immersed in top studies on biological chemistry of small molecules as a postdoctoral fellow at Harvard University, Department of Biological Chemistry (laboratory of Dr. Jacobsen, collaboration with Dr. Schreiber). I have 15 years of experience with scanning probe microscopy/atomic force microscopy of macromolecules, including giant enzymes, protein aggregates, and protein-nucleic acids complexes. My major current projects include:

1. Studying molecular dynamics and allosteric regulation of the proteasome. The two inherently related processes: molecular dynamics and allosteric responses, jointly govern the function of proteins. Understanding these processes in the proteasome, which is the essential part of intracellular proteostasis, will allow designing anti-cancer and anti-aging strategies. Atomic force microscopy (AFM) is one of my methods of choice. I introduced innovative use of AFM for monitoring protein dynamics and protein degradation.

2. Rational design, testing and elucidation of mechanism of small-molecule allosteric regulators of the proteasome. Competitive inhibitors of the proteasome are effective anti-cancer drugs used mostly in blood cancers. Allosteric regulators I created have a potential to kill solid cancer cells, alone or in synergistic action with competitive drugs.

3. Studying mechanisms of protein polymerization with atomic force microscopy. The proteins in the center of interest include serpins, aggregation of which is the culprit in serpinopathies, and amyloid beta polymers, one of causes of Alzheimer’s disease.

4. Exploring biophysical properties of cancer cells, aging cells and cells under stress in a search for robust diagnostic methods. Mechanical parameters of cell surface provide surprisingly universal clues about the physiological state of the whole cell. I use novel atomic force microscopy for monitoring the parameters. Currently am introducing an original scanning tunneling microscopy based method for monitoring the electrical properties of cell surface.


Selected Publications

  1. Giletto MB, Osmulski PA, Jones CL, Gaczynska ME, Tepe JJ. Pipecolic esters as minimized templates for proteasome inhibition. Org Biomol Chem. 2019;17(10):2734–2746.

  2. Njomen E, Osmulski PA, Jones CL, Gaczynska M, Tepe JJ. Small Molecule Modulation of Proteasome Assembly. Biochemistry. 2018 Jul 17;57(28):4214–4224.

  3. Giżyńska M, Witkowska J, Karpowicz P, Rostankowski R, Chocron ES, Pickering AM, Osmulski P, Gaczynska M, Jankowska E. Proline- and Arginine-Rich Peptides as Flexible Allosteric Modulators of Human Proteasome Activity. J Med Chem. 2019 Jan 10;62(1):359–370.

  4. Polusani SR, Huang Y-W, Huang G, Chen C-W, Wang C-M, Lin L-L, Osmulski P, Lucio ND, Liu L, Hsu Y-T, Zhou Y, Lin C-L, Aguilera-Barrantes I, Valente PT, Kost ER, Chen C-L, Shim EY, Lee SE, Ruan J, Gaczynska ME, Yan P, Goodfellow PJ, Mutch DG, Jin VX, Nicholson BJ, Huang TH-M, Kirma NB. Adipokines deregulate cellular communication via epigenetic repression of gap junction loci in obese endometrial cancer. Cancer Res. 2019;79(1):196–208.

  5. Gaczynska M, Osmulski PA, Jiang Y, Lee J-K, Bermudez V, Hurwitz J. Atomic force microscopic analysis of the binding of the Schizosaccharomyces pombe origin recognition complex and the spOrc4 protein with origin DNA. Proc Natl Acad Sci U S A. 2004;101(52):17952–17957.

  6. Gaczynska M, Osmulski PA. Targeting Protein–Protein Interactions in the Ubiquitin–Proteasome Pathway. In: Donev R, editor. Elsevier Inc.; 2018. p. 123–165.

  7. Osmulski PA and Gaczynska M: (2013) Rapamycin allosterically inhibits the proteasome. Mol Pharmacol. 84(1): 104-13.

  8. Edrey YE, Medina DX, Gaczynska M, Osmulski PA, Oddo S, Caccamo A, and Buffenstein R: (2013) Amyloid beta and the longest-lived rodent: the naked mole-rat as a model for natural protection from Alzheimer's disease. Neurobiol Aging. 34(10): 2352-60.

  9. Chen CL, Mahalingam D, Osmulski P, Jadhav RR, Wang CM, Leach RJ, Chang TC, Weitman SD, Kumar AP, Sun L, Gaczynska ME, Thompson IM, and Huang TH: (2013) Single-cell analysis of circulating tumor cells identifies cumulative expression patterns of EMT-related genes in metastatic prostate cancer. Prostate. 73(8): 813-26.

  10. Jankowska E, Stoj J, Karpowicz P, Osmulski PA, and Gaczynska M: (2013) The proteasome in health and disease. Curr Pharm Des. 19(6): 1010-28.

  11. Rodriguez KA, Edrey YH, Osmulski P, Gaczynska M, and Buffenstein R: (2012) Altered composition of liver proteasome assemblies contributes to enhanced proteasome activity in the exceptionally long-lived naked mole-rat. PLoS One. 7(5): e35890.

  12. Robinson AK, Leal BZ, Chadwell LV, Wang R, Ilangovan U, Kaur Y, Junco SE, Schirf V, Osmulski PA, Gaczynska M, Hinck AP, Demeler B, McEwen DG, and Kim CA: (2012) The growth-suppressive function of the polycomb group protein polyhomeotic is mediated by polymerization of its sterile alpha motif (SAM) domain. J Biol Chem. 287(12): 8702-13.

  13. Gaczynska M and Osmulski PA: (2011) Atomic force microscopy of proteasome assemblies. In: Atomic Force Microscopy in Biomedical Research: Methods and Protocols, Ed. Braga & Ricci., ISBN: 978-1-61779-104-8, Humana Press. DOI: 10.1007/978-1-61779-105-5_9 Series: Methods in Molecular Biology, 736: 117-132.

  14. Rodriguez KA, Gaczynska M, and Osmulski PA: (2010) Molecular mechanisms of proteasome plasticity in aging. Mech Ageing Dev. 131(2): 144-55.

  15. Jankowska E, Gaczynska M, Osmulski P, Sikorska E, Rostankowski R, Madabhushi S, Tokmina-Lukaszewska M, and Kasprzykowski F: (2010) Potential allosteric modulators of the proteasome activity. Biopolymers. 93(5): 481-95.

  16. Osmulski PA, Hochstrasser M, and Gaczynska M: (2009) A tetrahedral transition state at the active sites of the 20S proteasome is coupled to opening of the alpha-ring channel. Structure. 17(8): 1137-47.

  17. Rosenzweig R, Osmulski PA, Gaczynska M, and Glickman MH: (2008) The central unit within the 19S regulatory particle of the proteasome. Nat Struct Mol Biol. 15(6): 573-80.

  18. Gaczynska M and Osmulski PA: (2008) AFM of biological complexes: what can we learn? Curr Opin Colloid Interface Sci. 13(5): 351-67.

  19. Osmulski PA, Tokmina-Lukaszewska M, Endel L, Sosnowska R, Gaczynska M: (2008) Proteasome, Chemistry of. Wiley Encyclopedia of Chemical Biology

  20. Gaczynska M, Rodriguez K, Madabhushi S, and Osmulski PA: (2006) Highbrow proteasome in high-throughput technology. Expert Rev Proteomics. 3(1): 115-27.

  21. Gaczynska M and Osmulski PA: (2005) Characterization of noncompetitive regulators of proteasome activity. In: Ubiquitin and Protein Degradation, Part A Methods Enzymol. 398: 425-38. RJ Deshaies, ed., Elsevier.

  22. Osmulski PA and Gaczynska M: (2005) Atomic force microscopy of the proteasome. In: Ubiquitin and Protein Degradation, Part A Methods Enzymol. 398: 414-25. RJ Deshaies, ed., Elsevier.

  23. Gaczynska M, Osmulski PA, Jiang Y, Lee JK, Bermudez V, and Hurwitz J: (2004) Atomic force microscopic analysis of the binding of the Schizosaccharomyces pombe origin recognition complex and the spOrc4 protein with origin DNA. Proc Natl Acad Sci USA. 101(52): 17952-7.

  24. Yasmin R, Yeung KT, Chung RH, Gaczynska ME, Osmulski PA, and Noy N: (2004) DNA-looping by RXR tetramers permits transcriptional regulation "at a distance." J Mol Biol. 343(2): 327-38.

  25. Gaczynska M, Osmulski PA, Gao Y, Post MJ, and Simons M: (2003) Proline- and arginine-rich peptides constitute a novel class of allosteric inhibitors of proteasome activity. Biochemistry. 42(29): 8663-70. See comment: Drug Discov Today. 8(19): 866-8.

  26. Osmulski PA and Gaczynska M: (2002) Nanoenzymology of the 20S proteasome: proteasomal actions are controlled by the allosteric transition. Biochemistry. 41(22): 7047-53.

  27. Osmulski PA and Gaczynska M: (2000) Atomic force microscopy reveals two conformations of the 20S proteasome from fission yeast. J. Biol Chem. 275(18): 13171-4.

  28. Osmulski PA and Gaczynska M: (1998) A new large proteolytic complex distinct from the proteasome is present in the cytosol of fission yeast. Curr Biol. 8(18): 1023-6.