I study the stress or heat shock protein response, which is a highly conserved reaction to physical trauma and metabolic stress in most cells and organisms. It is a key feature of the way stressed or damaged cells and tissues can mitigate damage, retain or restore normal function, and even become more resistant to future stresses. The group of proteins that are part of this response are commonly referred to as heat shock proteins (Hsps). Because neurons are difficult to replace, this response is very important in the nervous system.
My collaborators and I have shown that some isoforms of the 70 kiloDalton Hsp (Hsp70) have potential as therapeutic agents that can rescue injured neurons and other cells.
Seifarth FG, Lax JE-M, Harvey J, Dicorleto PE, Husni ME, Chandrasekharan UM, Tytell M. (2018) Topical heat shock protein 70 prevents imiquimod-induced psoriasis-like inflammation in mice. Cell Stress and Chaperones, 23(5), 1129–1135. http://doi.org/10.1007/s12192-018-0895-0.
Tytell M, Davis AT, Giles J, Snider LC, Xiao R, Dozier SG, … Kavanagh K. (2017). Alfalfa-derived HSP70 administered intranasally improves insulin sensitivity in mice. Cell Stress and Chaperones, 70(2018), 1–6. http://doi.org/10.1007/s12192-017-0835-4.
Tytell M, Lasek RJ, & Gainer H. (2016). Axonal maintenance, glia, exosomes, and heat shock proteins. F1000Research, 5(F1000 Faculty Rev):205, http://doi.org/10.12688/f1000research.7247.1.
Hooper, P. L., Hooper, P. L., Tytell, M., Vígh, L. (2010). Xenohormesis: health benefits from an eon of plant stress response evolution. Cell Stress & Chaperones, 15(6), 761–70. http://doi.org/10.1007/s12192-010-0206-x.
Tytell, M., Robinson, M., Milligan, C. E. (2008). Release of heat shock proteins and their effects when in the extracellular space in the nervous system. In I. R. Asea, Alexzander A.A., Brown (Ed.), Heat Shock Proteins and the Brain: Implications for Neurodegenerative Diseases and Neuroprotection (Vol. 1, pp. 257–272). Dordrecht, The Netherlands: Springer Science+Business Media B.V.
Taylor, A. R., Robinson, M. B., Gifondorwa, D. J., Tytell, M., Milligan, C. E. (2007). Regulation of heat shock protein 70 release in astrocytes: role of signaling kinases. Developmental Neurobiology, 67(13), 1815–1829, pm:17701989.
Robinson MB, Tidwell JL, Gould T, Taylor AR, Newbern JM, Graves J, Tytell M, Milligan CE (2005) Extracellular heat shock protein 70: A critical component for motoneuron survival. J Neurosci 25: 9735-9745.
Tytell M (2005) Release of Heat Shock Proteins (Hsps) and the Effects of Extracellular Hsps on Neural Cells and Tissues. Int J Hyperthermia 21: 445-455.Seifarth FG, Lax JE-M, Harvey J, Dicorleto PE, Husni ME, Chandrasekharan UM, Tytell M. (2018) Topical heat shock protein 70 prevents imiquimod-induced psoriasis-like inflammation in mice. Cell Stress and Chaperones, 23(5), 1129–1135. http://doi.org/10.1007/s12192-018-0895-0.
Tytell M, Davis AT, Giles J, Snider LC, Xiao R, Dozier SG, … Kavanagh K. (2017). Alfalfa-derived HSP70 administered intranasally improves insulin sensitivity in mice. Cell Stress and Chaperones, 70(2018), 1–6. http://doi.org/10.1007/s12192-017-0835-4.
Tytell M, Lasek RJ, & Gainer H. (2016). Axonal maintenance, glia, exosomes, and heat shock proteins. F1000Research, 5(F1000 Faculty Rev):205, http://doi.org/10.12688/f1000research.7247.1.
Hooper, P. L., Hooper, P. L., Tytell, M., Vígh, L. (2010). Xenohormesis: health benefits from an eon of plant stress response evolution. Cell Stress & Chaperones, 15(6), 761–70. http://doi.org/10.1007/s12192-010-0206-x.
Tytell, M., Robinson, M., Milligan, C. E. (2008). Release of heat shock proteins and their effects when in the extracellular space in the nervous system. In I. R. Asea, Alexzander A.A., Brown (Ed.), Heat Shock Proteins and the Brain: Implications for Neurodegenerative Diseases and Neuroprotection (Vol. 1, pp. 257–272). Dordrecht, The Netherlands: Springer Science+Business Media B.V.
Taylor, A. R., Robinson, M. B., Gifondorwa, D. J., Tytell, M., Milligan, C. E. (2007). Regulation of heat shock protein 70 release in astrocytes: role of signaling kinases. Developmental Neurobiology, 67(13), 1815–1829, pm:17701989.
Robinson MB, Tidwell JL, Gould T, Taylor AR, Newbern JM, Graves J, Tytell M, Milligan CE (2005) Extracellular heat shock protein 70: A critical component for motoneuron survival. J Neurosci 25: 9735-9745.
Tytell M (2005) Release of Heat Shock Proteins (Hsps) and the Effects of Extracellular Hsps on Neural Cells and Tissues. Int J Hyperthermia 21: 445-455.
Tidwell JL, Houenou LJ, Tytell M (2004) Administration of Hsp70 in vivo inhibits motor and sensory neuron degeneration. Cell Stress & Chaperones 9: 88-98.
Dean DO, Tytell M (2001) Hsp25 and -90 immunoreactivity in the normal rat eye. Invest Ophthalmol Vis Sci 42: 3031-3040.
Tytell M, Hooper PL (2001) Heat shock proteins: new keys to the development of cytoprotective therapies. Emerging Therapeutic Targets 5: 267-287.
Yu Q, Kent CR, Tytell M (2001) Retinal uptake of intravitreally injected Hsc/Hsp70 and its effect on susceptibility to light damage. Molec Vis 7: 48-56.
Guzhova I, Kislyakova K, Moskoliova O, Fridlanskaya I, Tytell M, Cheetham M, Margulis B (2001) In vitro studies show that Hsp70 can be released by glia and that exogenous Hsp70 can enhance neuronal stress tolerance. Brain Res 914: 66-73.
Dean DO, Kent CR, and Tytell M (1999) Constitutive and inducible heat shock protein 70 immunoreactivity in the normal rat eye. Invest. Ophthalmol. Vis. Sci. 40:2952-2962.
Tytell M, Brown WR, Moody DM, and Challa VR (1998) Immunohistochemical assessment of constitutive and inducible heat-shock protein 70 and ubiquitin in human cerebellum and caudate nucleus. Molec. Chem. Neuropathol. 35:97-117.
Houenou LJ, Li L, Lei M, Kent CR, and Tytell M (1996) Exogenous heat shock cognate protein (hsp) 70 prevents axotomy-induced death of spinal sensory neurons. Cell Stress & Chaperones 1:161-166.
Tytell M, Barbe MF and Brown IR (1994) Induction of heat shock (stress) protein 70 and its mRNA in the normal and light-damaged rat retina after whole body hyperthermia. J. Neurosci. Res. 38:19-31.
Barbe MF, Tytell M, Gower DJ and Welch WJ (1988) Hyperthermia protects against light damage in the rat retina. Science, 241:1817-1820.
Tidwell JL, Houenou LJ, Tytell M (2004) Administration of Hsp70 in vivo inhibits motor and sensory neuron degeneration. Cell Stress & Chaperones 9: 88-98.
Dean DO, Tytell M (2001) Hsp25 and -90 immunoreactivity in the normal rat eye. Invest Ophthalmol Vis Sci 42: 3031-3040.
Tytell M, Hooper PL (2001) Heat shock proteins: new keys to the development of cytoprotective therapies. Emerging Therapeutic Targets 5: 267-287.
Yu Q, Kent CR, Tytell M (2001) Retinal uptake of intravitreally injected Hsc/Hsp70 and its effect on susceptibility to light damage. Molec Vis 7: 48-56.
Guzhova I, Kislyakova K, Moskoliova O, Fridlanskaya I, Tytell M, Cheetham M, Margulis B (2001) In vitro studies show that Hsp70 can be released by glia and that exogenous Hsp70 can enhance neuronal stress tolerance. Brain Res 914: 66-73.
Dean DO, Kent CR, and Tytell M (1999) Constitutive and inducible heat shock protein 70 immunoreactivity in the normal rat eye. Invest. Ophthalmol. Vis. Sci. 40:2952-2962.
Tytell M, Brown WR, Moody DM, and Challa VR (1998) Immunohistochemical assessment of constitutive and inducible heat-shock protein 70 and ubiquitin in human cerebellum and caudate nucleus. Molec. Chem. Neuropathol. 35:97-117.
Houenou LJ, Li L, Lei M, Kent CR, and Tytell M (1996) Exogenous heat shock cognate protein (hsp) 70 prevents axotomy-induced death of spinal sensory neurons. Cell Stress & Chaperones 1:161-166.
Tytell M, Barbe MF and Brown IR (1994) Induction of heat shock (stress) protein 70 and its mRNA in the normal and light-damaged rat retina after whole body hyperthermia. J. Neurosci. Res. 38:19-31.
Barbe MF, Tytell M, Gower DJ and Welch WJ (1988) Hyperthermia protects against light damage in the rat retina. Science, 241:1817-1820.
Tytell M, Davis AT, Giles J, Snider LC, Xiao R, Dozier SG, … Kavanagh K. (2017). Alfalfa-derived HSP70 administered intranasally improves insulin sensitivity in mice. Cell Stress and Chaperones, 70(2018), 1–6. http://doi.org/10.1007/s12192-017-0835-4.
Tytell M, Lasek RJ, & Gainer H. (2016). Axonal maintenance, glia, exosomes, and heat shock proteins. F1000Research, 5(F1000 Faculty Rev):205, http://doi.org/10.12688/f1000research.7247.1.
Hooper, P. L., Hooper, P. L., Tytell, M., Vígh, L. (2010). Xenohormesis: health benefits from an eon of plant stress response evolution. Cell Stress & Chaperones, 15(6), 761–70. http://doi.org/10.1007/s12192-010-0206-x.
Tytell, M., Robinson, M., Milligan, C. E. (2008). Release of heat shock proteins and their effects when in the extracellular space in the nervous system. In I. R. Asea, Alexzander A.A., Brown (Ed.), Heat Shock Proteins and the Brain: Implications for Neurodegenerative Diseases and Neuroprotection (Vol. 1, pp. 257–272). Dordrecht, The Netherlands: Springer Science+Business Media B.V.
Taylor, A. R., Robinson, M. B., Gifondorwa, D. J., Tytell, M., Milligan, C. E. (2007). Regulation of heat shock protein 70 release in astrocytes: role of signaling kinases. Developmental Neurobiology, 67(13), 1815–1829, pm:17701989.
Robinson MB, Tidwell JL, Gould T, Taylor AR, Newbern JM, Graves J, Tytell M, Milligan CE (2005) Extracellular heat shock protein 70: A critical component for motoneuron survival. J Neurosci 25: 9735-9745.
Tytell M (2005) Release of Heat Shock Proteins (Hsps) and the Effects of Extracellular Hsps on Neural Cells and Tissues. Int J Hyperthermia 21: 445-455.Seifarth FG, Lax JE-M, Harvey J, Dicorleto PE, Husni ME, Chandrasekharan UM, Tytell M. (2018) Topical heat shock protein 70 prevents imiquimod-induced psoriasis-like inflammation in mice. Cell Stress and Chaperones, 23(5), 1129–1135. http://doi.org/10.1007/s12192-018-0895-0.
Tytell M, Davis AT, Giles J, Snider LC, Xiao R, Dozier SG, … Kavanagh K. (2017). Alfalfa-derived HSP70 administered intranasally improves insulin sensitivity in mice. Cell Stress and Chaperones, 70(2018), 1–6. http://doi.org/10.1007/s12192-017-0835-4.
Tytell M, Lasek RJ, & Gainer H. (2016). Axonal maintenance, glia, exosomes, and heat shock proteins. F1000Research, 5(F1000 Faculty Rev):205, http://doi.org/10.12688/f1000research.7247.1.
Hooper, P. L., Hooper, P. L., Tytell, M., Vígh, L. (2010). Xenohormesis: health benefits from an eon of plant stress response evolution. Cell Stress & Chaperones, 15(6), 761–70. http://doi.org/10.1007/s12192-010-0206-x.
Tytell, M., Robinson, M., Milligan, C. E. (2008). Release of heat shock proteins and their effects when in the extracellular space in the nervous system. In I. R. Asea, Alexzander A.A., Brown (Ed.), Heat Shock Proteins and the Brain: Implications for Neurodegenerative Diseases and Neuroprotection (Vol. 1, pp. 257–272). Dordrecht, The Netherlands: Springer Science+Business Media B.V.
Taylor, A. R., Robinson, M. B., Gifondorwa, D. J., Tytell, M., Milligan, C. E. (2007). Regulation of heat shock protein 70 release in astrocytes: role of signaling kinases. Developmental Neurobiology, 67(13), 1815–1829, pm:17701989.
Robinson MB, Tidwell JL, Gould T, Taylor AR, Newbern JM, Graves J, Tytell M, Milligan CE (2005) Extracellular heat shock protein 70: A critical component for motoneuron survival. J Neurosci 25: 9735-9745.
Tytell M (2005) Release of Heat Shock Proteins (Hsps) and the Effects of Extracellular Hsps on Neural Cells and Tissues. Int J Hyperthermia 21: 445-455.
Tidwell JL, Houenou LJ, Tytell M (2004) Administration of Hsp70 in vivo inhibits motor and sensory neuron degeneration. Cell Stress & Chaperones 9: 88-98.
Dean DO, Tytell M (2001) Hsp25 and -90 immunoreactivity in the normal rat eye. Invest Ophthalmol Vis Sci 42: 3031-3040.
Tytell M, Hooper PL (2001) Heat shock proteins: new keys to the development of cytoprotective therapies. Emerging Therapeutic Targets 5: 267-287.
Yu Q, Kent CR, Tytell M (2001) Retinal uptake of intravitreally injected Hsc/Hsp70 and its effect on susceptibility to light damage. Molec Vis 7: 48-56.
Guzhova I, Kislyakova K, Moskoliova O, Fridlanskaya I, Tytell M, Cheetham M, Margulis B (2001) In vitro studies show that Hsp70 can be released by glia and that exogenous Hsp70 can enhance neuronal stress tolerance. Brain Res 914: 66-73.
Dean DO, Kent CR, and Tytell M (1999) Constitutive and inducible heat shock protein 70 immunoreactivity in the normal rat eye. Invest. Ophthalmol. Vis. Sci. 40:2952-2962.
Tytell M, Brown WR, Moody DM, and Challa VR (1998) Immunohistochemical assessment of constitutive and inducible heat-shock protein 70 and ubiquitin in human cerebellum and caudate nucleus. Molec. Chem. Neuropathol. 35:97-117.
Houenou LJ, Li L, Lei M, Kent CR, and Tytell M (1996) Exogenous heat shock cognate protein (hsp) 70 prevents axotomy-induced death of spinal sensory neurons. Cell Stress & Chaperones 1:161-166.
Tytell M, Barbe MF and Brown IR (1994) Induction of heat shock (stress) protein 70 and its mRNA in the normal and light-damaged rat retina after whole body hyperthermia. J. Neurosci. Res. 38:19-31.
Barbe MF, Tytell M, Gower DJ and Welch WJ (1988) Hyperthermia protects against light damage in the rat retina. Science, 241:1817-1820.
Tidwell JL, Houenou LJ, Tytell M (2004) Administration of Hsp70 in vivo inhibits motor and sensory neuron degeneration. Cell Stress & Chaperones 9: 88-98.
Dean DO, Tytell M (2001) Hsp25 and -90 immunoreactivity in the normal rat eye. Invest Ophthalmol Vis Sci 42: 3031-3040.
Tytell M, Hooper PL (2001) Heat shock proteins: new keys to the development of cytoprotective therapies. Emerging Therapeutic Targets 5: 267-287.
Yu Q, Kent CR, Tytell M (2001) Retinal uptake of intravitreally injected Hsc/Hsp70 and its effect on susceptibility to light damage. Molec Vis 7: 48-56.
Guzhova I, Kislyakova K, Moskoliova O, Fridlanskaya I, Tytell M, Cheetham M, Margulis B (2001) In vitro studies show that Hsp70 can be released by glia and that exogenous Hsp70 can enhance neuronal stress tolerance. Brain Res 914: 66-73.
Dean DO, Kent CR, and Tytell M (1999) Constitutive and inducible heat shock protein 70 immunoreactivity in the normal rat eye. Invest. Ophthalmol. Vis. Sci. 40:2952-2962.
Tytell M, Brown WR, Moody DM, and Challa VR (1998) Immunohistochemical assessment of constitutive and inducible heat-shock protein 70 and ubiquitin in human cerebellum and caudate nucleus. Molec. Chem. Neuropathol. 35:97-117.
Houenou LJ, Li L, Lei M, Kent CR, and Tytell M (1996) Exogenous heat shock cognate protein (hsp) 70 prevents axotomy-induced death of spinal sensory neurons. Cell Stress & Chaperones 1:161-166.
Tytell M, Barbe MF and Brown IR (1994) Induction of heat shock (stress) protein 70 and its mRNA in the normal and light-damaged rat retina after whole body hyperthermia. J. Neurosci. Res. 38:19-31.
Barbe MF, Tytell M, Gower DJ and Welch WJ (1988) Hyperthermia protects against light damage in the rat retina. Science, 241:1817-1820.
About Me
I investigate how cells protect themselves from physical trauma and metabolic stress, especially in the nervous system. My research has focused on understanding the role of a highly conserved family of proteins, commonly referred to as heat shock proteins or Hsps, in making cells more resistant to injury or promote their survival injury. Over more than 30 years, I and collaborators at Wake Forest and elsewhere have documented that one of the more abundant of the Hsps, called Hsp70, can be used as a therapeutic agent to rescue damaged retinal and neural cells. We now understand that the cytoprotective activity of Hsp70 results from its ability to keep other cellular proteins properly folded and to modulate the immune response.
I have also been involved in graduate student professional training. I contributed to the development of classes in research ethics and to an internship program for Ph.D. and M.S. students to gain work experience beyond the conventional lab bench research.