MACKLIS LAB

Bradley Molyneaux
Paola Arlotta
Noriyuki Kishi
Jason Emsley
Pembe Hande Ozdinler
Joao Meneze
Shivraj Sohur

Denis Jabaudon
Tina Lai
Arthur Czupryn

Liyun Li
Bartley Mitchell
Sanjay Magavi

Justine M. Nagurney

Kyle MacQuarrie
Alexander Eswar

MGH-HMS Center for Nervous System Repair
Jeffrey Macklis, M.D., D. HST.

Please go to our new web site: macklis.mgh.harvard.edu

Jeffrey D. Macklis MGH-HMS Center for Nervous System Repair MGH main campus Edwards Research 4 Telephone: 617-724-0678 Email: jeffrey_macklis@hms.harvard.edu Predocs: 3 Postdocs: 9 Completed PhD's: 3 Macklis Biosketch Macklis Publications

Main areas of lab interest:

1) cellular repair of complex cortical circuitry and cortical output circuitry;
2) molecular controls over adult neurogenesis and differentiation of neural precursors/stem cells into specific cortical projection neuron lineages;
3) neural transplantation and activity-dependent / molecular enhancement of integration;
4) function of adult-born neurons, olfactory neurogenesis and learning

Our laboratory has two central areas of investigation, and one emerging direction: 1) cellular repair of neocortical circuitry via induction of adult cortical neurogenesis and control of transplanted neuroblasts/neural precursors/stem cells; 2) neocortical projection neuron development-- molecular controls over neural and neuronal precursors that guide their specific lineage differentiation, connections, and survival; 3) functional analysis of complex convergent and divergent neuronal networks, particularly networks with adult neurogenesis and new neuron incorporation.

The combined long-term objectives of this research are to apply cellular and molecular control mechanisms to reconstruct complex neocortical projection neuron circuitry by neural transplantation or manipulation of recently identified, endogenous neural precursors. Much of our past and current work has focused on repair by transplantation of immature neurons / neural precursors / neural stem cells. Ultimately, however, repair may also be possible by manipulation of endogenous neural precursors / stem cells without transplantation. This approach is the focus of much of our recent and ongoing work. These approaches could lead to therapies for neurodegenerative disease, developmental disorders, or acquired disease of the neocortex or its output circuitry, including the cortico-spinal motor system centrally involved in ALS and spinal cord injury. This research also aims toward a better understanding of normal and perturbed cortical projection neuron development, important for understanding the etiology of a number of developmental nervous system disorders. The third aspect of our work is directed at rigorous functional analysis of reconstructed CNS circuitry, and investigation of the function of adult neurogenesis in circuits in which adult neurogenesis occurs.

Selected references (see also Recent Publications):

Magavi, S.S., Leavitt, B.R., Macklis, J.D. (2000) Induction of neurogenesis in the neocortex of adult mice. Nature; 405: 951-955.

Scharff, C., Kirn, J., M. Grossman, Macklis, J.D.*, Nottebohm, F. (2000) Targeted neuronal death affects neuronal replacement and vocal behavior in adult songbirds. Neuron; 25: 481-492. (*co-senior authors)

Shin, J.J., Fricker-Gates, R.A., Perez, F.A., Leavitt, B.R., Zurakowski, D., Macklis, J.D. (2000) Transplanted neuroblasts differentiate appropriately into projection neurons with correct neurotransmitter and receptor phenotype in neocortex undergoing targeted projection neuron degeneration. J Neurosci.; 20: 7404-7416.

Gates, M.A., Tai, C.C., Macklis, J.D. Neocortical neurons lacking the protein-tyrosine kinase B (TrkB) receptor display abnormal differentiation and process elongation in vitro and in vivo. Neuroscience. 2000; 98: 437-447.

Catapano, L.A., Arnold, M.W., Perez, F.A., Macklis, J.D. (2001) Specific neurotrophic factors support the survival of cortical projection neurons at distinct stages of development. J Neurosci, 21(22): 8863-8872.

Fricker-Gates, R.A., Shin J.J., Tai, C.C., Catapano, L.A., Macklis, J.D. Late stage immature neocortical neurons reconstruct interhemispheric connections and form synaptic contacts with increased efficiency in adult mouse cortex undergoing targeted neurodegeneration. 2002. J Neurosci, 22(10): 4045-4056.

Eyding D, Macklis JD, Neubacher U, Funke K, Worgotter F. Selective elimination of corticogeniculate feedback abolishes the electroencephalogram dependence of primary visual cortical receptive fields and reduces their spatial specificity. J Neurosci. 2003 Aug 6;23(18):7021-33.

Catapano LA, Arlotta P, Cage TA, Macklis JD. Stage-specific and opposing roles of BDNF, NT-3 and bFGF in differentiation of purified callosal projection neurons toward cellular repair of complex circuitry. Eur J Neurosci. 2004 May;19(9):2421-34.

Mitchell, B.D., Macklis, J.D. Large-scale maintenance of dual projections by callosal and frontal cortical projection neurons in adult mice. Minor revision under review at J Comp Neurol, 2004.

Kishi, N., Macklis, J.D. MECP2 is progressively expressed in post-migratory neurons and is involved in neuronal maturation rather than cell fate decisions. Mol Cell Neurosci. 2004 Nov;27(3):306-21.

Chen, J., Magavi, S.S.P., Macklis, J.D. Neurogenesis of corticospinal motor neurons extending spinal projections in adult mice. Proc Natl Acad Sci U S A. 2004 Nov 16;101(46):16357-16362. Epub 2004 Nov 8.

Macklis Lab (MGH-HMS Center for Nervous System Repair):

	Name	Time Period	Education
Predoc	Bradley Molyneaux	(2001-present)	BS 1999 Dartmouth College
Postdoc	Paola Arlotta	(2000-present)	Ph.D. 2000 Portsmouth University, UK and Harvard Medical School
Postdoc	Noriyuki Kishi	(2001-present)	M.D.- Ph.D. 2001 Osaka University
Postdoc	Jason Emsley	(2002(July)-present)	Ph.D. 2002 Dalhousie University
Postdoc	Pembe Hande Ozdinler	(2002 (Oct)-present)	Ph.D. 2002 University of Louisiana
Postdoc	Joao Menezes	(2003(Aug)-present)	M.D.- Ph.D. Fed Univ Rio de Janeiro
Postdoc	Shivraj Sohur	(2004(Jul)-present)	M.D. - Ph.D. - Vanderbilt University School of Medicine

New to the Lab:

Postdoc	Denis Jabaudon	September 2004, Education- MD, PhD, 2000-University of Zurich, Switzerland
Postdoc	Tina Lai	October 2004, Education- M.A., Yale University, PhD, 2003-UC Berkeley
Postdoc	Artur Czupryn	(October 2004) Education- Education-MSc., Warsaw University, Poland, 1997, PhD-NENCKI Institute, Warsaw, Poland-2002

Lab Alumni:

	Liyun Li
Postdoc	Bartley Mitchell	(2001-2004)	Ph.D. 2000 University of Texas
Postdoc	Sanjay Magavi	(2001-2004)	Ph.D. 2001 Harvard University

	Howard Hughes Medical Institute		Masland HHMI Lab Description
	HHMI Neuroscience Biomedical Research		Masland HMS Lab Description
	Harvard Medical School		HMS Ph.D. Programs in the Division of Medical Sciences