Print Version
ALEXEY TERSKIKH, PH.D.
Assistant Professor
Stem Cells and Regenerative Biology
858.795.5299 (phone)
858.795.5298 (fax)
terskikh@burnham.org
RESEARCH FOCUS, BIOGRAPHY, STAFF, PUBLICATIONS
Research Focus
My research interest is focused on the mechanisms of self-renewal and differentiation of stem cells. We are investigating both cellular and molecular aspects of these processes using human embryonic stem cells (hESCs) as well as mouse neural stem cells. We have recently developed a unique system allowing uniform differentiation of hESCs into multipotent neural precursors, allowing us to investigate the early events during hESCs differentiation and to test the strategies for stem cell therapies. We are also fascinated with the biology of Maternal Embryonic Leucine zipper Kinase (MELK), working in close collaboration with the laboratory of Harley Kornblum, UCLA.
Biography
Alexey Terskikh earned his Ph.D. at the University of Lausanne, Switzerland in 1996, in the laboratory of Prof. J.-P. Mach, where he designed a new type of high-avidity recombinant molecule called Peptabody. He received postdoctoral training with Prof. Irving Weissman at Stanford University, where he discovered a common genetic program between hematopoietic and neural stem cells. Dr. Terskikh holds an Assistant Professor position in the Brain and Mind Institute at EPFL in Lausanne, Switzerland (2002-2006) and was recruited to the Burnham Institute for Medical Research as Adjunct Assistant Professor in 2002 and as a full time Assistant Professor in 2006.
Publications
Terskikh AV, Bryant PJ, Schwartz PH. Mammalian stem cells. Pediatr Res. 2006 Apr;59(4 Pt 2):13R-20R.
Surdez D, Kunz B, Wagers AJ, Weissman IL, Terskikh AV. Simple and efficient isolation of hematopoietic stem cells from H2K-zFP transgenic mice. Stem Cells. 2005 Nov-Dec;23(10):1617-25.
Terskikh AV, Easterday MC, Li L, Hood L, Kornblum HI, Geschwind DH, Weissman IL. From hematopoiesis to neuropoiesis: evidence of overlapping genetic programs. Proc Natl Acad Sci U S A. 2001 Jul 3;98(14):7934-9.
Terskikh A, Fradkov A, Ermakova G, Zaraisky A, Tan P, Kajava AV, Zhao X, Lukyanov S, Matz M, Kim S, Weissman I, Siebert P. "Fluorescent timer": protein that changes color with time. Science. 2000 Nov 24;290(5496):1585-8.
List of Publications via PubMed
(NIH National Library of Medicine)
Research Report
Therapeutic Potential of Human ES Cell-Derived Neural Precursors with Uniform Characteristics
(In collaboration with Stuart Lipton, BIMR and Lindsay Whitton, Scripps).
The derivation of well-characterized, uniform human neural precursor cells (hNPCs) is critical for future cell-based therapies of neurodegenerative and traumatic diseases in the brain. High-throughput drug screens also require uniform populations of hNPCs. Here we develop a new, efficient procedure for the rapid (~12 d) differentiation of human embryonic stem cells (hESCs) into uniform neural precursors (hES-NPCs) that was hitherto unachievable. Cell-based proteome profiling demonstrates reproducible differentiation of hESCs that have been expanded over 1015 fold. In culture, hES-NPCs become functional neurons and myelin-producing oligodendrocytes. After transplantation into neonatal brain, hES-NPCs migrate and differentiate into neurons appropriate to their location, e.g., into olfactory bulb and cerebrocortical neurons and myelinate the congenitally dismyelinated shiverer mouse brain. In the adult brain, systemic administration of hES-NPCs rescues cuprizone-induced demyelination of the corpus callosum. Thus, the uniform hES-NPC population described in this study provides a convenient source of neural cell types for transplantation and high-throughput drug screening.
 |
hES-NPCs express homogenous array of pro-neural markers. (A) Analysis of markers characteristic for undifferentiated hESC, mesoderm, and endoderm using RT-PCR in hES cells and hES-NPCs. (B) Immunostaining for the developmental markers, left column fluorescent antibody, right column overlay with nuclear DAPI (blue). Staining for nuclear Oct4, a marker for undifferentiated human ES cells (absent); pro-neural markers like nuclear Sox2 (uniformly present), cytoplasmic Musashi1 (uniformly present), filamentous Nestin (uniformly present); committed neuronal markers such as cytoplasmic TuJ1 (<0.1%) and MAP2 (absent). |
Maternal Embryonic Leucine zipper Kinase (MELK) Regulates Multipotent Neural Progenitor Proliferation
(In collaboration with Harley Kornblum, UCLA)
Maternal embryonic leucine zipper kinase (MELK) was previously identified in a screen for genes enriched in neural progenitors. Here, we demonstrate
expression of MELK by progenitors in developing and adult brain and that MELK serves as a marker for selfrenewing multipotent neural progenitors (MNPs) in cultures derived from the developing forebrain and in transgenic mice. Overexpression of MELK enhances (whereas knockdown diminishes) the ability to generate neurospheresfrom MNPs, indicating a function in self-renewal. MELK down-regulation disrupts the production of neurogenic MNP from glial fibrillary acidic protein (GFAP)–positive progenitors in vitro. MELK expression in MNP is cell cycle regulated and inhibition of MELK expression down-regulates the expression of B-myb, which is shown to also mediate MNP proliferation. These findings indicate that MELK is necessary for proliferation of embryonic and postnatal MNP and suggest that it regulates the transition from GFAP-expressing progenitors to rapid amplifying progenitors in the postnatal brain.
 |
| MELK-EGFP transgenic mice recapitulated the expression pattern of endogenous MELK in CNS. Expression of EGFP in a P8 transgenic mouse demonstrating specific signal in the subventricular zone (SVZ) (b, c), dentate gyrus of hippo-campus (DG) (d), and granule cell layer in cerebellum (e), all indicated by arrows. |
