Robert Miller, Ph.D.

Robert Miller, Ph.D.
Adjunct Professor
Department of Neurosciences
Case Western Reserve University


School of Medicine, Room E653
10900 Euclid Ave
Cleveland OH, 44106-4975

Phone : (216) 368-6269
Fax : (216) 368-4650
Email : rhm3@case.edu
 
 

RESEARCH INTERESTS

The laboratory combines a primary interest in CNS neural development with a focus on understanding the biology of neural diseases including Multiple Sclerosis, Brain tumors and Cerebral Palsy.

Development

We are interested in understanding the cellular and molecular mechanisms that regulate glial cell determination in the developing vertebrate CNS. Oligodendrocytes, the myelinating cells of the CNS develop from precursors that arise in distinct locations within the embryonic neural tube. The origin of oligodendrocyte precursors is a result of local signaling including expression of sonic hedgehog. A number of other influences are required to develop the final pattern of oligodendrocyte in the mature tissue. These include dispersal signals to guide cell migration and stop signals such as the chemokine CXCL1 that position precursors to receive appropriate proliferative and differentiative cues. We are currently defining the interplay between these different signals in order to gain a complete understanding of oligodendrogenesis.

Disease

Multiple Sclerosis

Precursor cells capable of giving rise to oligodendrocytes persist in the adult CNS and we are using a variety of approaches to determine whether these endogenous cells can be recruited to enhance repair of damaged white matter in the adult CNS. These include stimulation of cell proliferation and survival through delivery of specific proteins into focal lesions and the use of transgenic mice lacking critical components of the chemokine signal pathways.

Brain tumors

The majority of primary brain tumors are derived from glial lineage cells. Using information derived from out developmental studies we are determining whether distinct populations of brain tumors proliferate migrate and die in response to selected stimuli.

Cerebral Palsy

Cerebral Palsy is a commonly associated with insults to the developing CNS that result in aberrant development of myelinated regions. We are testing the hypothesis that the failure of normal development reflects a transient perturbation in the development of oligodendrocyte precursors. We have recently developed a novel model of fetal ischemia in rats and are using this model to develop interventional therapies to reduce the damage of prenatal insults.

olig-progression-final-copy.jpg  

SELECTED PUBLICATIONS

  1. Miller RH. (2006)
    The promise of stem cells for neural repair. Brain Res. 2006 Mar 21;
  2. Tsai HH, Macklin WB, Miller RH. (2006)
    Netrin-1 is required for the normal development of spinal cord oligodendrocytes. J Neurosci. 2006 Feb 15; 26(7):1913-1922.
  3. Patzer JF 2nd, Safta SA, Miller RH. (2006)
    Slow continuous ultrafiltration with bound solute dialysis. ASAIO J. 2006 Jan-Feb; 52(1):47-58.
  4. Gao L, Macklin W, Gerson J, Miller RH. (2006)
    Intrinsic and extrinsic inhibition of oligodendrocyte development by rat retina. Dev Biol. 2006 Feb 15; 290(2):277-286. 2006/01/04 [aheadofprint].
  5. Bambakidis NC, Theodore N, Nakaji P, Harvey A, Sonntag VK, Preul MC, Miller RH. (2005)
    Endogenous stem cell proliferation after central nervous system injury: alternative therapeutic options. Neurosurg Focus. 2005 Sep 15; 19(3):E1.
  6. Miller RH, West C, Brown TM, Sim I, Ganchoff C. (2005)
    The value of electronic health records in solo or small group practices. Physicians' EHR adoption is slowed by a reimbursement system that rewards the volume of services more than it does their quality. Health Aff (Millwood). 2005 Sep-Oct; 24(5):1127-1137.
  7. Coleson JL, Miller RH. (2005)
    Antibiosis and antixenosis to Aphis gossypii (Homoptera: Aphididac) in Colocasia esculenta. J Econ Entomol. 2005 Jun; 98(3):996-1006.
  8. Sussman CR, Vartanian T, Miller RH. (2005)
    The ErbB4 neuregulin receptor mediates suppression of oligodendrocyte maturation. J Neurosci. 2005 Jun 15; 25(24):5757-5762.
  9. Mi S, Miller RH, Lee X, Scott ML, Shulag-Morskaya S, Shao Z, Chang J, Thill G, Levesque M, Zhang M, Hession C, Sah D, Trapp B, He Z, Jung V, McCoy JM, Pepinsky RB. (2005)
    LINGO-1 negatively regulates myelination by oligodendrocytes. Nat Neurosci. 2005 Jun; 8(6):745-751. 2005/05/15 [aheadofprint].
  10. Robinson S, Petelenz K, Li Q, Cohen ML, Dechant A, Tabrizi N, Bucek M, Lust D, Miller RH. (2005)
    Developmental changes induced by graded prenatal systemic hypoxic-ischemic insults in rats. Neurobiol Dis. 2005 Apr; 18(3):568-581.
  11. Miller RH. (2005)
    Dorsally derived oligodendrocytes come of age. Neuron. 2005 Jan 6; 45(1):1-3.
  12. Miller RH, Dinsio K, Wang R, Geertman R, Maier CE, Hall AK. (2004)
    Patterning of spinal cord oligodendrocyte development by dorsally derived BMP4. J Neurosci Res. 2004 Apr 1; 76(1):9-19.
  13. Bambakidis NC, Miller RH. (2004)
    Transplantation of oligodendrocyte precursors and sonic hedgehog results in improved function and white matter sparing in the spinal cords of adult rats after contusion. Spine J. 2004 Jan-Feb; 4(1):16-26.
  14. Jacobsen CT, Miller RH. (2003)
    Control of astrocyte migration in the developing cerebral cortex. Dev Neurosci. 2003 Mar-Aug; 25(2-4):207-216.
  15. Bambakidis NC, Wang RZ, Franic L, Miller RH. (2003)
    Sonic hedgehog-induced neural precursor proliferation after adult rodent spinal cord injury. J Neurosurg. 2003 Jul; 99(1 Suppl):70-75.
  16. Tsai HH, Tessier-Lavigne M, Miller RH. (2003)
    Netrin 1 mediates spinal cord oligodendrocyte precursor dispersal. Development. 2003 May; 130(10):2095-2105.
  17. Baracskay KL, Duchala CS, Miller RH, Macklin WB, Trapp BD. (2002)
    Oligodendrogenesis is differentially regulated in gray and white matter of jimpy mice. J Neurosci Res. 2002 Dec 1; 70(5):645-654.
  18. Miller RH. (2002)
    Regulation of oligodendrocyte development in the vertebrate CNS. Prog Neurobiol. 2002 Aug; 67(6):451-467.
  19. Sussman CR, Davies JE, Miller RH. (2002)
    Extracellular and intracellular regulation of oligodendrocyte development: roles of Sonic hedgehog and expression of E proteins. Glia. 2002 Oct; 40(1):55-64.
  20. Tsai HH, Frost E, To V, Robinson S, Ffrench-Constant C, Geertman R, Ransohoff RM, Miller RH. (2002)
    The chemokine receptor CXCR2 controls positioning of oligodendrocyte precursors in developing spinal cord by arresting their migration. Cell. 2002 Aug 9; 110(3):373-383.
  21. Tsai HH, Miller RH. (2002)
    Glial cell migration directed by axon guidance cues. Trends Neurosci. 2002 Apr; 25(4):173-5; discussion 175.
  22. Viehover A, Miller RH, Park SK, Fischbach G, Vartanian T. (2001)
    Neuregulin: an oligodendrocyte growth factor absent in active multiple sclerosis lesions. Dev Neurosci. 2001; 23(4-5):377-386.
  23. Nakatsuji Y, Miller RH. (2001)
    Control of oligodendrocyte precursor proliferation mediated by density-dependent cell cycle protein expression. Dev Neurosci. 2001; 23(4-5):356-363.
  24. Nakatsuji Y, Miller RH. (2001)
    Density dependent modulation of cell cycle protein expression in astrocytes. J Neurosci Res. 2001 Nov 1; 66(3):487-496.
  25. Davies JE, Miller RH. (2001)
    Local sonic hedgehog signaling regulates oligodendrocyte precursor appearance in multiple ventricular zone domains in the chick metencephalon. Dev Biol. 2001 May 15; 233(2):513-525.
  26. Robinson S, Cohen M, Prayson R, Ransohoff RM, Tabrizi N, Miller RH. (2001)
    Constitutive expression of growth-related oncogene and its receptor in oligodendrogliomas. Neurosurgery. 2001 Apr; 48(4):864-73; discussion 873.
  27. Noll EN, Lin J, Nakatsuji Y, Miller RH, Black PM. (2001)
    GM3 as a novel growth regulator for human gliomas. Exp Neurol. 2001 Apr; 168(2):300-309.
  28. Nakatsuji Y, Miller RH. (2001)
    Selective cell-cycle arrest and induction of apoptosis in proliferating neural cells by ganglioside GM3. Exp Neurol. 2001 Apr; 168(2):290-299.
  29. Wu Q, Miller RH, Ransohoff RM, Robinson S, Bu J, Nishiyama A. (2000)
    Elevated levels of the chemokine GRO-1 correlate with elevated oligodendrocyte progenitor proliferation in the jimpy mutant. J Neurosci. 2000 Apr 1; 20(7):2609-2617.
  30. Sussman CR, Dyer KL, Marchionni M, Miller RH. (2000)
    Local control of oligodendrocyte development in isolated dorsal mouse spinal cord. J Neurosci Res. 2000 Feb 1; 59(3):413-420.
  31. Miller RH, Hayes JE, Dyer KL, Sussman CR. (1999)
    Mechanisms of oligodendrocyte commitment in the vertebrate CNS. Int J Dev Neurosci. 1999 Dec; 17(8):753-763.
  32. Miller RH. (1999)
    Contact with central nervous system myelin inhibits oligodendrocyte progenitor maturation. Dev Biol. 1999 Dec 1; 216(1):359-368.
  33. Ueda H, Levine JM, Miller RH, Trapp BD. (1999)
    Rat optic nerve oligodendrocytes develop in the absence of viable retinal ganglion cell axons. J Cell Biol. 1999 Sep 20; 146(6):1365-1374.
  34. Orentas DM, Hayes JE, Dyer KL, Miller RH. (1999)
    Sonic hedgehog signaling is required during the appearance of spinal cord oligodendrocyte precursors. Development. 1999 Jun; 126(11):2419-2429.
 
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