Jon Holy, PhD

Associate Professor, Medical School, Duluth Campus

Jon Holy

Contact Info

Office Phone 218-726-7902

Fax 218-726-7937

Office Address:
Department of Biomedical Sciences
213 SMed
1035 University Dr
Duluth, MN 55812

Associate Professor, Medical School, Duluth Campus

Postdoctoral, University of Wisconsin-Madison, Cell/Molecular Biology, 1988-1993

PhD, Anatomy, University of Wisconsin – Madison, 1988

MS, University of Wisconsin- Eau Claire, Zoology, 1983

BS, University of Wisconsin- Eau Claire, Biology/Psychology, 1978


Research Summary/Interests

Primary areas of research interest include studying cell behavioral responses to natural, synthetic, and semisynthetic compound candidates for cancer chemotherapy, including investigating the role of the physical microenvironment in mechanotransduction and chemotherapeutic action using three-dimensional in vitro culture systems. Recent projects are focused on exploring the interplay between microenvironmental compliance, the expression of certain C2H2 zinc finger transcriptional regulators, and their modulation by mevalonate pathway inhibitors. Collaborative studies have included using two-photon fluorescence polarization anisotropy of NADH to study cell metabolic responses to novel perturbants of glycolysis and oxidative phosphorylation (Drs. A. Heikal and V. Mereddy, Univ. of MN Duluth), and the actions of natural and semi-synthetic mitochondrial-targeting compounds on various tumor cell lines (Dr. P. Krasutsky, NRRI, and the MitoXT research group of the CNC led by Dr. P. Oliveira, Univ. Coimbra, Portugal).


See full list of publication at: PubMed

Baldeiras, I, Erickson, JR, Holy, J, Potes, Y, Coto-Montes, A, Oliveira, PJ, and Vega-Naredo, I. 2020. Cell quality control mechanisms maintain stemness and differentiation potential of P19 embryonic carcinoma cells. Autophagy 16:313-333.

Cong, A, Pimenta, RML, Lee, HB, Mereddy, V, Holy, J, and Heikal, AA. 2019. Two-photon fluorescence lifetime imaging of intrinsic NADH in three-dimensional tumor models. Cytometry A. 95:80-92.

Jonnalagadda, S, Jonnalagadda,. SK, Ronayne, CT, Nelson, GL, Solano, LN, Rumbley, J, Holy, J, Mereddy, VR, and Drewes, LR. 2019. Novel N,N-dialkl cyanocinnamic acids as monocarboxylate transporter 1 and 4 inhibitors. Oncotarget 10:2355-2368.

Nelson, G.L., Ronayne, C.RT., Solano, L.N., Jonnalagadda, S.K., Jonnalagadda, S., Rumbley, J., Holy, J., Rose-Hellekant, T., Drewes, L.R., and Mereddy, V.R. 2019 Development of novel silyl cyanocinnamic acid derivatives as metabolic plasticity inhibitors for cancer treatment. Sci. Rep. 9:18266.

Carvalho, F.S., Morais, C.M., Holy, J., Krasutsky, D., Yemets, S.V., Kresutsky, P.A., Jurado, A.S., Oliveira, P.J., and Serafim, T.L. 2018. Toxicity of lupine derivatives on anionic membrane models, isolated rat mitochondria and selected human cell lines: role of terminal alkyl chains. Chem. Biol. Interact. 296:198-210.

Zhou, K., Diebel, K.W., Holy, J., Skildum A., Odean E., Hicks D.A., Schotl B., Abrahante J.E., Spillman M.A., Bemis L.T. 2017. A tRNA fragment, tRF5-Glu, regulates BCAR3 expression and proliferation in ovarian cancer cells. Oncotarget 8:95377-95391.

Ronayne, C.T., Solano, L.N., Nelson, G.L., Lueth, E.A., Hubbard, S.L., Schumacher, T.J., Gardner, Z.S., Jonnalagadda, S.K., Gurrapu, S., Holy, J., Mereddy, V.R. 2017. Synthesis and biological evaluation of 2-alkoxycarbonylallyl esters as potential anticancer agents. Bioorg Med Chem Lett. 27:776-780.

Berens, E.B., Holy, J.M., Riegel, A.T., and Wellstein, A. 2015. A cancer cell spheroid assay to assess invasion in a 3D setting. J. Vis. Exp. 105:53409.

Moreira, A.C., Branco, A.F., Sampaio, S.F., Cunha-Oliveira, T., Martins, T.R., Holy, J., Oliveira, P.J., and Sardao, V.A. 2014. Mitochondrial apoptosis-inducing factor is involved in doxorubicin-induced toxifity on H9C2 cardiomyoblasts. Biochim. Biophys. Acta 1842 (12 Pt. A):2468-2478.

Vega-Naredo I, Loureiro R, Mesquita KA, Barbosa IA, Tavares LC, Branco AF, Erickson JR, Holy J, Perkins EL, Carvalho RA, and Oliveira PJ. 2014. Mitochondrial metabolism directs stemness and differentiation in P19 embryonal carcinoma stem cells. Cell Death Differ. 21:1560-1574.

Oliveira, P.J., Perkins, E.L., and Holy, J. 2014. Vital imaging of multicellular spheroids. Methods Mol. Biol. 1075: 227-241.

Serafim, T.L., Carvalho, F.S., Bernardo, T.C., Pereira, G.C., Perkins, E., Holy, J., Krasutsky, D.A., Kolomitsyna, O.N., Krasutsky, P.A., and Oliveira, P.J. 2014. New derivatives of lupine triterpenoids disturb breast cancer mitochondria and induce cell death. Bioorg. Med. Chem. 22:6270-6287.

Hu, W., Holy, J., and Yu, X. 2013. Fibroblast behavior on PMMAEA and PMMAEA-collagen films and nanofibers. J. Nanomat. Mol. Nanotechnol. 2:1-6.

Bernardo TC, Cunha-Oliveira T, Serafim TL, Holy J, Krasutsky D, Kolomitsyna O, Krasutsky P, Moreno AM, and Oliveira PJ. 2013. Dimethylaminopyridine derivatives of lupane triterpenoids cause mitochondrial disruption and induce the permeability transition. Bioorg. Med. Chem. 21:7239-7249.

Branco, A.F., Pereira, S.L., Moreira, A.C., Holy, J., Sardão, V.A., and Oliveira, P.J. 2011 Isoproterenol cytotoxicity is dependent on the differentiation state of the cardiomyoblast H9C2 cell line. Cardiovasc. Toxicol. 11:191-203.

Serafim, T., Carvalho, F. Marques, M., Calheiros, R., Silva, T., Garrido, J., Milhazes, N., Borges, F., Roleira, F., Tavares da Silva, E., Holy, J., Oliveira, P. 2011. Lipophilic Caffeic and ferulic acid derivatives presenting cytotoxicity against human breast cancer cells. Chem. Res. Toxicol. 24:763-774.

Fiúza, S.M., Holy, J., Batista de Carvalho, L.A., and Marques, M.P. 2011. Biological activity of a dinuclear Pd(II)-spermine complex towards human breast cancer. Chem. Biol. Drug Design 77:477-488.

Holy, J., Perkins, E., and X. Yu. 2011. Adhesion, proliferation, and differentiation of pluripotent stem cells on multiwalled carbon nanotubes. IET Nanobiotechnology 5:41-46.

Holy, J., Kolomitsyna, O., Krasutsky, D., Oliveira, P.J., Perkins, E., and P.A. Krasutsky. 2010. Dimethylaminopurine derivatives of lupane triterpenoids are potent disruptors of mitochondrial structure and function. Bioorg. Med. Chem. 18:6080-6088.

Sardao, V., Rose-Hellekant, T., Perkins, E., Greene, A., and J. Holy. 2010. Measuring reciprocal regulation of mesenchymal stem cell and tumor cell motility in two and three dimensions in vitro. In: Cytoskeleton: Cell Movement, Cytokinesis and Organelles Organization, S. Lansing and T. Rousseau, Eds. Nova Science Pub. Inc.

Holy, J., Perkins, E., and X. Yu. 2009. Differentiation of pluripotent stem cells on multiwalled carbon nanotubes. Conf. Proc. IEEE Eng. Med. Biol. Soc. 2009:6022-6025.

Sardao, V.A., Oliveira, P.J., Holy, J, Oliveira, C., and Wallace, K.B. 2009. Doxorubicin-induced mitochondrial dysfunction is secondary to nuclear p53 activation in H9c2 cardiomyoblasts. Cancer Chemother. Pharmacol. 64:811-827.

Holy, J., and E. Perkins. 2009. Structure and function of the nucleus and cell organelles. In: Bioinformatics for systems biology: second edition, Introduction to Bioinformatics (ed. S. Krawetz), Humana Press, Totowa, NJ.

Oliveira, P.J., E. Perkins, and J. Holy. 2008. Vital imaging of multicellular spheroids. Methods in Confocal Microscopy, S. Paddock, ed.

Serafim, T.L., Matos, J.A., Sardão, V.A., Pereira, G.C., Branco, A.F., Pereira, S.L., Parke, D. Perkins, E.L., Santos, M.S., Moreno, A.J.M., Holy, J., Oliveira, P.J. 2008. Sanguinarine cytotoxicity on mouse melanoma K1735-M2 cells – nuclear versus mitochondrial effects. Biochem. Pharmacol. 76:1459-1475.

Sardao, V.A., Oliveira, P.J., Holy, J, Oliveira, C.R., and K.B. Wallace. 2008. Morphological alterations induced by doxorubicin on H9c2 myoblasts: nuclear, mitochondrial, and cytoskeletal targets. Cell Biol. Toxicol.

Serafim, T., Oliveira, P.J., Sardao, V., Perkins, E., Parke, D., and Holy, J. 2008. Different concentrations of berberine result in distinct cellular localization patterns and cell cycle effects in a melanoma cell line. Cancer Chemother. Pharmacol. 61:1007-1018.

Pereira, G.C., Branco, A.F., Matos, J.A.C., Pereira, S.L., Parke. D., Perkins, E.L., Serafim, T.L., Sardão, V.M., Santos, M.S., Moreno, A.J.M., Holy, J.M., Oliveira, P.J. 2007. Mitochondrially-targeted effects of berberine on K1735-M2 mouse melanoma cells: comparison with direct effects on isolated mitochondrial fractions. J. Pharmacol. Exp. Therap. 323:636-649.

Kolomitsyn, I., Holy, J., Perkins, E., and P. Krasutsky. 2007. Analysis and antiproliferative activity of bark extractives of Betula neoalaskana and B. papyrifera. Synthesis of the most active extractive component - Betulin 3-Caffeate. Nat. Prod. Comm. 2:17-26.

Sardao, V.A., P.J. Oliveira, J. Holy, C.R. Oliveira, and K.B. Wallace. 2007. Vital imaging of H9C2 myoblasts exposed to tert-butylhydroperoxide – characterization of morphological features of cell death. BMC Cell Biol. 8:11

Holy, J., G. Lamont, and E. Perkins. 2006. Disruption of nucleocytoplasmic trafficking of cyclin D1 and topoisomerase II by sanguinarine. BMC Cell Biol. 7:13-25.

Alves, L., L. de Mendonca Lima, E. da Silva Maeda, L. Carvalho, J. Holy, E.N. Sarno, M.C.V. Pessolani and L. Barker. 2004. Mycobacterium leprae infection of human schwann cells depends on selective host kinases and pathogen-modulated endocytic pathways. FEMS Microbiol. Lett. 238:429-437.

Holy, J. 2004. Curcumin inhibits cell motility and alters microfilament organization and function in prostate cancer cells. Cell Motil. Cytoskel. 58:253-268.

Rolo AP, Palmeira CM, Holy JM, Wallace KB. 2004. Role of mitochondrial dysfunction in combined bile acid-induced cytotoxicity: the switch between apoptosis and necrosis. Toxicol. Sci. 79:196-204.

Lamont, G. and J.M. Holy. 2003. Comparison of the effects of alkaloids present in traditional native american medicinal plants on melanoma and breast cancer cell lines. McNair Schol. J. 4:1-25.

Holy, J. 2003. Structure and function of cell organelles. In: Introduction to Bioinformatics (eds. S. Krawetz and D. Womble), Humana Press, Totowa, NJ (pp. 25-54).

Holy, J. 2002. Curcumin disrupts mitotic spindle structure and induces micronucleation in MCF-7 breast cancer cells. Mutation Res. 518:71-84.

Gorny, G.A., and J.H. Holy. 2002. Effects of curcumin on LNCaP prostate cancer cells. McNair Schol. J. 3:47-57

Holy, J. 2000. Intermediate filament proteins in echinoderm coelomocytes. Comp. Biochem. Biophys. 127:491-504.

Pierce, T., Worman, H.J., and J. Holy. 1999. Neuronal differentiation of NT2/D1 teratocarcinoma cells is accompanied by a loss of lamin A/C expression and an increase in lamin B expression. Exp. Neurol. 157:241-250

Holy, J. 1998. Imaging fertilization. In: Protocols in Confocal Microscopy (S. Paddock, ed.), Humana Press Inc., Totowa, NJ.

Holy, J. 1998. Chlorpropham (N-(3-chlorophenyl)carbamate) disrupts microtubule organization, cell division, and early development of sea urchin embryos. J. Toxicol. Env. Health 54: 319-333.

Flynn, K., P. Schoff, and J. Holy. 1998. Localization of eurasian ruffe testicular antigens identified by a panel of monoclonal antibodies. J. Great Lakes Res. 24:379-382.

Holy, J., and C. Chong. 1997. Quantitative immunofluorescence analyses of nuclear lamin breakdown during echinoderm coelomocyte cell death. M.D.I.B.L. Bulletin 36:7-10.

Holy, J., and G. Schatten. 1997. Recruitment of maternal material during assembly of the zygote centrosome in fertilized sea urchin eggs. Cell Tiss. Res. 289:285-297.

Henson, J.H., C.D. Roesener, C.J. Gaetano, R.J. Mendola, J.N. Forrest, J. Holy, and A. Kleinzeller. 1997. Confocal microscopic observation of cytoskeletal reorganizations in cultured shark rectal gland cells following treatment with hypotonic shock and high external K+. J. Exp. Zool. 279:415-424.

Holy, J. 1996. Conserved expression of a single B-type nuclear lamin in different tissues of the sea urchin.Biochem. Biophys. Res. Comm. 222:531-536.

Holy, J., G. Wessel, L. Berg, R. Gregg, and G. Schatten. 1995. Molecular characterization and expression patterns of a B-type nuclear lamin during sea urchin embryogenesis. Dev. Biol. 168:464-478.

Oaks, J.A., and J.M. Holy. 1994. Hymenolepis diminuta: two morphologically distinct tegumental secretory mechanisms are present in the cestode. Exp. Parasitol.79:292-300.

Holy, J., and G. Schatten. 1991. Spindle pole centrosomes of sea urchin embryos are partially composed of material recruited from maternal stores. Dev. Biol. 147:343-353.

Kay, B.K., J.P. Evans, E.C. Raff, E.C. Stephenson, M.L. King, D.L. Gard, M.W. Klymkowsky, R.P. Elinson, J.M. Holy and S. Strome. 1991. The cytoskeletons of gametes, eggs and early embryos. In: Cell-Cell Interactions in Early Development. J.C. Gerhart, Ed. Wiley-Liss Inc, New York.

Holy, J., C. Simerly, S. Paddock, and G. Schatten. 1991. Three-dimensional imaging of fertilization and early development. J. Electron Microsc. Tech. 17:384-400.

Holy, J., and G. Schatten. 1991. Differential behavior of centrosomes in unequally dividing blastomeres during fourth cleavage of sea urchin embryos. J. Cell Sci. 98:423-431.

Holy, J.M., J.A. Oaks, M. Mika-Grieve, and R. Grieve. 1991. Development and dynamics of regional specialization in the syncytial epidermis of the rat tapeworm, Hymenolepis diminuta. Parasitol. Res. 77:161-172.

Holy, J., and G. Schatten. 1990. Laser scanning confocal microscopy and 3-D reconstruction of the mitotic spindles of unequally dividing embryonic cells. Proc. XIIth Int. Cong. Elect. Microsc. 3:166-167.

Paddock, S., P. DeVries, J. Holy and G. Schatten. 1990. On laser scanning confocal microscopy and three dimensional volume rendering of biological structures. Proc. Soc. Photo-Optical Inst. Eng. 1205:169-178.

Sobkowicz, H.M., J. Holy, and G.L. Scott. 1989. Ultrastructure of the intercalated body, a novel organelle associated with the fluid forming cells in the organ of Corti. J. Electron Microsc. Tech. 15:301-315.

Holy, J.M., and J.A. Oaks. 1989. Cytoskeletal features of the syncytial epidermis of the tapeworm Hymenolepis diminuta. Cell Motil. Cytoskel. 13:41-56.

Abraham, D., R.B. Grieve, J.M. Holy, and B.M. Christian. 1989. Immunity to larval Brugia malayi in Balb/c mice: protective immunity and inhibition of larval development. Am. J. Trop. Med. Hyg. 40:598-604.

Holy, J.M., K.A. O’Leary, J.A. Oaks and J.W. Tracy. 1989. Immunocytochemical localization of the major glutathione S-transferases in adult Schistosoma mansoni. J. Parasitol. 75:181-190.

Holy, J.M., and J.A. Oaks. 1987. Mechanical integration of muscle, tegument, and sub-tegumental tissues by fibrils and microfibrils in the cestode Hymenolepis diminuta. Tiss. Cell 19:881-891.

Holy, J.M., and J.A. Oaks. 1987. Cytoskeletal features of epithelia prepared by “extractive fixation.” Proc. Electron Microsc. Soc. Am. 45:902-903.

Holy, J.M., and D.W. Wittrock. 1986. Ultrastructure of the female reproductive organs (ovary, vitellaria and Mehlis’gland) of Halipegus eccentricus (Trematoda, Derogenidae). Can. J. Zool. 64:2203-2212.

Holy, J.M., and J.A. Oaks. 1986. Ultrastructure of the tegumental microvilli (microtriches) of Hymenolepis diminuta. Cell Tiss. Res. 244:457-466.

Peterson, D.M., R.H. Saigo, and J. Holy. 1985. Development of oat aleurone cells and their protein bodies.Cereal Chem. 62:366-371.

Sobkowicz, H.M., J.E. Rose, G.L. Scott, and J.M. Holy. 1984. The ultrastructure of the developing organ of Corti in culture. In: Ultrastructural Atlas of the Inner Ear, I. Friedmann and J. Ballantyne, Eds. Butterworths, London.

Saigo, R.H., D.M. Peterson, and J. Holy. 1983. Development of protein bodies in oat starchy endosperm. Can. J. Bot. 61:1206-1215.


Teaching Areas

Cell Biology

Mentoring/Advising: undergraduate students, graduate students, and post doctoral researchers.