Theo Palmer 博士
助理教授
斯坦福大学
tpalmer@stanford.edu
Theo D. Palmer, Ph.D.
Assistant Professor
Stanford University Program in Neurosciences
Departments of Neurosurgery and Neurology
MSLS P304, MC 5487, 1201 Welch Rd.
Stanford, CA 94305-5487
USA
研究方向
Dr. Palmer joined the Neuroscience Faculty at Stanford University in 2000 and holds appointments as Assistant Professor in the Departments of Neurosurgery and Neurology, with an additional appointment by courtesy to The Parkinsons Institute, Sunnyvale, California. Dr. Palmer was born in Los Angeles California and gained his Bachelors of Science degree in 1981 from Andrews University in Berrien Springs Michigan. His PhD in Experimental Pathology was awarded in 1990 by the University of Washington and Fred Hutchinson Cancer Research Center in Seattle. In postdoctoral studies with Dr. Fred H. Gage at the Salk Institute in La Jolla, California, Dr. Palmer developed many of the methods he currently uses to study neural stem cell function and regeneration in the developing and adult brain.
Dr. Palmers current research activities include studies in natural adult neural stem cell function as well as the use of embryonic, fetal and adult stem cells in the repair of neurological injury and disease. A particular focus is placed on the role of immune processes in modifying the behavior of endogenous or transplanted stem cells within the injured brain. Dr. Palmer is actively involved in establishing cooperative programs in brain restoration that have engaged leading groups from Europe, the US, Korea and China in an effort to accelerate the safe and effective application stem cell biology in neurological injury and disease. Current global projects highlight opportunities for the treatment of Parkinsons disease and for improving patient cognitive ability and quality of life in the aftermath of stroke or brain cancer.
Research Interests
In human brain development, neurogenesis ceases at birth and the vast majority of areas in the adult mammalian brain no longer produce new neurons, even in the face of debilitating injury or disease. However, there are distinct exceptions to the rule. In rodents and humans, the hippocampus is one of the few areas where neurogenesis continues throughout life. Among other roles, the hippocampus is most well known as the area of the brain that mediates short-term learning and memory. Hippocampal function is affected in many diseases with grave human consequences. The two most common presentations of this dysfunction are memory deficits that accompany Alzheimer’s disease and major depressive disorders. The fact that the addition/replacement of neurons uniquely occurs in the hippocampus suggests that neurogenesis itself plays a useful role within a pre-existing neural network. However, the mechanisms that regulate this process are not understood.
Our research examines regions of adult brain where neurogenesis occurs to understand how the brain regulates and utilizes this ability to add or replace neurons. In our anatomical studies in the adult rodent hippocampus, it has become clear that neurons are produced by neural stem cells that reside in a specialized environmental niche at the interface between neural tissues of the brain and a vascular bed of fine capillaries. It is likely that the areas permissive for neurogenesis in the adult are defined by a specific arrangement of cells and signals from both the CNS and the periphery. To define how these diverse cellular signals collaborate to control neurogenesis in the adult, we have been reconstructing neurogenesis in the brain and Petri dish using primary cultures of neural stem cells and precursor cells derived from humans, rats and mice. This work has allowed us to identify specific growth factors, such as vascular endothelial growth factor, insulin-like growth factor-1, sonic hedgehog and wingless family members that act on neural precursors to promote neurogenesis, but only when stem/progenitor cells are located within the correct local niche. By further defining this context-dependent regulation of neural stem cells at four levels (proliferation, differentiation, migration and survival), we hope to identify the specific cues that regulate where and when new neurons are made.
The local activation of neuronal replacement in other areas of the brain, or the reconstruction of a “neurogenic” niche through cell transplantation promise to be fundamentally important clinical tools for brain repair but an understanding of how neurogenesis is regulated and how is presence or absence influences cognition and behavior is critical for guiding these efforts. With sufficient insights into the natural utilization of neural stem cells, it will be possible to manipulate the workings of the mind to ameliorate the devastating effects of disease or injury.
Publications
Soen Y, Mori A, Palmer TD, Brown PO "Exploring the regulation of human neural precursor cell differentiation using arrays of signaling microenvironments." Mol Syst Biol 2006; 2: 37
Deisseroth K, Singla S, Toda H, Monje M, Palmer TD, Malenka RC "Excitation-neurogenesis coupling in adult neural stem/progenitor cells." Neuron 2004; 42: 4: 535-52
Wurmser AE, Palmer TD, Gage FH "Neuroscience. Cellular interactions in the stem cell niche." Science 2004; 304: 5675: 1253-5
Monje ML, Toda H, Palmer TD "Inflammatory blockade restores adult hippocampal neurogenesis." Science 2003; 302: 5651: 1760-5
Monje ML, Mizumatsu S, Fike JR, Palmer TD "Irradiation induces neural precursor-cell dysfunction." Nat Med 2002; 8: 9: 955-62
Ormerod BK, Palmer TD, Caldwell MA "Neurodegeneration and cell replacement." Philos Trans R Soc Lond B Biol Sci 2007;
Hairston IS, Little MT, Scanlon MD, Barakat MT, Palmer TD, Sapolsky RM, Heller HC "Sleep restriction suppresses neurogenesis induced by hippocampus-dependent learning." J Neurophysiol 2005;
Hoehn BD, Palmer TD, Steinberg GK "Neurogenesis in Rats After Focal Cerebral Ischemia is Enhanced by Indomethacin." Stroke 2005; 36: 12: 2718-2724
Markakis EA, Palmer TD, Randolph-Moore L, Rakic P, Gage FH "Novel neuronal phenotypes from neural progenitor cells." J Neurosci 2004; 24: 12: 2886-97
Limoli CL, Giedzinski E, Rola R, Otsuka S, Palmer TD, Fike JR "Radiation response of neural precursor cells: linking cellular sensitivity to cell cycle checkpoints, apoptosis and oxidative stress." Radiat Res 2004; 161: 1: 17-27
Fabel K, Fabel K, Tam B, Kaufer D, Baiker A, Simmons N, Kuo CJ, Palmer TD "VEGF is necessary for exercise-induced adult hippocampal neurogenesis." Eur J Neurosci 2003; 18: 10: 2803-12
Aberg MA, Aberg ND, Palmer TD, Alborn AM, Carlsson-Skwirut C, Bang P, Rosengren LE, Olsson T, Gage FH, Eriksson PS "IGF-I has a direct proliferative effect in adult hippocampal progenitor cells." Mol Cell Neurosci 2003; 24: 1: 23-40
Toda H, Tsuji M, Nakano I, Kobuke K, Hayashi T, Kasahara H, Takahashi J, Mizoguchi A, Houtani T, Sugimoto T, Hashimoto N, Palmer TD, Honjo T, Tashiro K "Stem cell-derived neural stem/progenitor cell supporting factor is an autocrine/paracrine survival factor for adult neural stem/progenitor cells." J Biol Chem 2003; 278: 37: 35491-500
Mizumatsu S, Monje ML, Morhardt DR, Rola R, Palmer TD, Fike JR "Extreme sensitivity of adult neurogenesis to low doses of X-irradiation." Cancer Res 2003; 63: 14: 4021-7
Horner PJ, Palmer TD "New roles for astrocytes: the nightlife of an 'astrocyte'. La vida loca!" Trends Neurosci 2003; 26: 11: 597-603
Palmer TD, "Adult neurogenesis and the vascular Nietzsche." Neuron 2002; 34: 6: 856-8
van Praag H, Schinder AF, Christie BR, Toni N, Palmer TD, Gage FH "Functional neurogenesis in the adult hippocampus." Nature 2002; 415: 6875: 1030-4
Moore EE, Presnell S, Garrigues U, Guilbot A, LeGuern E, Smith D, Yao L, Whitmore TE, Gilbert T, Palmer TD, Horner PJ, Kuestner RE "Expression of IL-17B in neurons and evaluation of its possible role in the chromosome 5q-linked form of Charcot-Marie-Tooth disease." Neuromuscul Disord 2002; 12: 2: 141-50
Kuhn HG, Palmer TD, Fuchs E "Adult neurogenesis: a compensatory mechanism for neuronal damage." Eur Arch Psychiatry Clin Neurosci 2001; 251: 4: 152-8
Palmer TD, Schwartz PH, Taupin P, Kaspar B, Stein SA, Gage FH "Cell culture. Progenitor cells from human brain after death." Nature 2001; 411: 6833: 42-3
Palmer TD, Willhoite AR, Gage FH "Vascular niche for adult hippocampal neurogenesis." J Comp Neurol 2000; 425: 4: 479-94
Horner PJ, Power AE, Kempermann G, Kuhn HG, Palmer TD, Winkler J, Thal LJ, Gage FH "Proliferation and differentiation of progenitor cells throughout the intact adult rat spinal cord." J Neurosci 2000; 20: 6: 2218-28
Palmer TD, Markakis EA, Willhoite AR, Safar F, Gage FH "Fibroblast growth factor-2 activates a latent neurogenic program in neural stem cells from diverse regions of the adult CNS." J Neurosci 1999; 19: 19: 8487-97
Sakurada K, Ohshima-Sakurada M, Palmer TD, Gage FH "Nurr1, an orphan nuclear receptor, is a transcriptional activator of endogenous tyrosine hydroxylase in neural progenitor cells derived from the adult brain." Development 1999; 126: 18: 4017-26
Takahashi J, Palmer TD, Gage FH "Retinoic acid and neurotrophins collaborate to regulate neurogenesis in adult-derived neural stem cell cultures." J Neurobiol 1999; 38: 1: 65-81
Shihabuddin LS, Palmer TD, Gage FH "The search for neural progenitor cells: prospects for the therapy of neurodegenerative disease." Mol Med Today 1999; 5: 11: 474-80
Takahashi M, Palmer TD, Takahashi J, Gage FH "Widespread integration and survival of adult-derived neural progenitor cells in the developing optic retina." Mol Cell Neurosci 1998; 12: 6: 340-8
Gage FH, Kempermann G, Palmer TD, Peterson DA, Ray J "Multipotent progenitor cells in the adult dentate gyrus." J Neurobiol 1998; 36: 2: 249-66
Palmer TD, Takahashi J, Gage FH "The adult rat hippocampus contains primordial neural stem cells." Mol Cell Neurosci 1997; 8: 6: 389-404
Gage FH, Coates PW, Palmer TD, Kuhn HG, Fisher LJ, Suhonen JO, Peterson DA, Suhr ST, Ray J "Survival and differentiation of adult neuronal progenitor cells transplanted to the adult brain." Proc Natl Acad Sci U S A 1995; 92: 25: 11879-83
Palmer TD, Ray J, Gage FH "FGF-2-responsive neuronal progenitors reside in proliferative and quiescent regions of the adult rodent brain." Mol Cell Neurosci 1995; 6: 5: 474-86
Palmer TD, Miller AD, Reeder RH, McStay B "Efficient expression of a protein coding gene under the control of an RNA polymerase I promoter." Nucleic Acids Res 1993; 21: 15: 3451-7
Ramesh N, Lau S, Palmer TD, Storb R, Osborne WR "High-level human adenosine deaminase expression in dog skin fibroblasts is not sustained following transplantation." Hum Gene Ther 1993; 4: 1: 3-7
Palmer TD, Rosman GJ, Osborne WR, Miller AD "Genetically modified skin fibroblasts persist long after transplantation but gradually inactivate introduced genes." Proc Natl Acad Sci U S A 1991; 88: 4: 1330-4
Thompson AR, Palmer TD, Lynch CM, Miller AD "Gene transfer as an approach to cure patients with hemophilia A or B." Curr Stud Hematol Blood Transfus 1991; 58: 59-62
Palmer TD, Thompson AR, Miller AD "Production of human factor IX in animals by genetically modified skin fibroblasts: potential therapy for hemophilia B." Blood 1989; 73: 2: 438-45
Bender MA, Palmer TD, Gelinas RE, Miller AD "Evidence that the packaging signal of Moloney murine leukemia virus extends into the gag region." J Virol 1987; 61: 5: 1639-46
Palmer TD, Hock RA, Osborne WR, Miller AD "Efficient retrovirus-mediated transfer and expression of a human adenosine deaminase gene in diploid skin fibroblasts from an adenosine deaminase-deficient human." Proc Natl Acad Sci U S A 1987; 84: 4: 1055-9
Miller AD, Palmer TD, Hock RA "Transfer of genes into human somatic cells using retrovirus vectors." Cold Spring Harb Symp Quant Biol 1986; 51 Pt 2: 1013-9
