Siddharthan Chandran PhD MRCP

MRC Clinical Scientist Fellow          E-mail: sc222@cam.ac.uk

The group is interested in (1) Human stem cells (embryonic and adult) with a focus on glial origins and (2) In vitro mechanisms of glial-neuronal interaction in the context of clinical translation for diseases such as Multiple Sclerosis.  We are part of the Neurology Group headed up by Alastair Compston.

Improved understanding of the genetic and signalling requirements that underlie the generation of differentiated progeny from human neural stem cells may enable therapeutic application of such cells.  We have demonstrated the differential potential and requirement of hedgehog signalling for human and rodent neural stem cells to generate oligodendrocytes.  Ongoing projects are concerned with further understanding the requirement for hedgehog signalling and its relationship to FGF in the specification of oligodendrocytes from human embryonic stem cells and examining the in vitro and in vivo 'stem cell' potential of oligodendrocyte precursors.

An important cause of disability in multiple sclerosis is axonal injury.  Using in vitro models of neuronal and glial injury we have shown the importance of oligodendroglial derived trophic signals and ongoing projects are concerned with further understanding the relationship between injury and axonal damage.

Collaborations

• Maeve Caldwell - we work closely with the Caldwell group in all stem cell projects.
• Roger Pedersen - human embryonic stem cells.
• Nick Allen - manipulation of neural cell fate from embryonic stem cells.
• Jane Sterling - neural potential of adult human skin precursors.

Recent publications

1. Joannides A, Gaughwin P, Schwiening C, Majed H, Sterling J, Comspton A, Chandran S.  Efficient generation of neural precursors from adult human skin: astrocytes promote neurogenesis from skin-derived stem cells.  Lancet in press.
2. Chandran S, Compston A, Jauniaux E, Gilson J, Blakemore W, Svendsen C.  Differential generation of oligodendrocytes from human and rodent embryonic spinal cord neural precursor.  Glia in press.
3. Joannides A, Gaughwin P, Scott M, Watt S, Compston A, Chandran S.  Postnatal astrocytes promote neural induction from adult human bone marrow-derived stem cells.  J. Hematotherapy & Stem Cell Research  in press.
4. Chandran S, Kato H, Gerreli D, Compston A, Svendsen CN, Allen ND.  FGF dependent generation of oligodendrocytes by a hedgehog independent pathway.  Development.  2003; 130: 6599-609.
5. Wilkins A, Majed H, Layfield R, Compston A, Chandran S.  Oligodendrocytes promote neural survival and axonal length by distinct intracellular mechanisms: a novel role for oligodendrocyte derived GDNF.  J. Neuroscience.  2003; 23: 4967-74.
6. Zarei M, Chandran S, Compston A, Hodges J.  Cognitive presentation of multiple sclerosis: evidence for a cortical variant.  Journal of Neurology, Neurosurgery and Psychiatry.  2003; 74: 872-77.
7. Golde S, Chandran S, Brown G, Compston A.  Different mechanisms for INOS mediated toxicity depending on neuronal maturation and NMDA receptor expression.  J. Neurochemistry.  2002; 82; 269-82.
8. Zarei M, Collins VP, Chandran S, Valler D, Higgins JNP, Compston DAS, Yates JRW.  An exceptionally mild case of tuberous sclerosis presenting in late adult life.  JNNP.  2002; 73: 46-8.
9. Wilkins A, Chandran S, Compston A.  A role of oligodendrocyte derived IGF-1 in trophic support of cortical neurons.  Glia.  2001; 36: 48-57.
10. Chandran S, Svendsen C, Compston A, Scolding N.  Regional potential for oligodendrocyte generation in the rodent embryonic spinal cord following exposure to EGF and FGF-2.  Glia.  1998; 24: 382-9.
11. Svendsen CN, Armstrong RJ, Rosser AE, Chandran S, Ostenfeld T, Caldwell MA.  A new method for the rapid and long term growth of human neural precursor cells.  J.Neurosci.Methods.  1998; 85: 141-52.