BBS Faculty Member - Jeffrey Macklis

Jeffery Macklis

Max and Anne Wien Professor of Life Sciences
Department of Stem Cell and Regenerative Biology, and Center for Brain Science, Harvard University
Professor of Neurology [Neuroscience] and of Surgery [Neurosurgery], Harvard Medical School



Harvard University
Bauer Laboratory 103
7 Divinity Avenue
Cambridge, MA 02138
Tel: 617-495-5413
Fax: 617-496-9679
Email: jeffrey_macklis@harvard.edu
Lab Members: 7 postdoctoral fellows, 4 graduate students
Visit my lab page here.



Our laboratory is directed toward both 1) understanding the molecular controls over neuron sub-type specification and development in the cerebral cortex, and 2) applying developmental controls toward brain and spinal cord repair—specifically, the cellular repair of complex cerebral cortex and cortical output circuitry (in particular, corticospinal motor neuron (CSMN) circuitry that degenerates in ALS and other “upper motor neuron” degenerative diseases, and whose injury is centrally involved in loss of motor function in spinal cord injury).

We focus on neocortical projection neuron development and sub-type specification; neural progenitor / “stem cell” biology; induction of adult neurogenesis (the birth of new neurons from within); and directed neuronal differentiation and development of connectivity via molecular manipulation of neural progenitors within murine neocortex. The same biology informs understanding of neuronal subtype specificity of involvement in human neurodegenerative and developmental diseases, in particular ALS / motor neuron disease, PLS, HSPs, Huntington's disease, autism spectrum disorders, and Rett Syndrome.

Toward this goal, and toward the basic goal of understanding neocortical neuronal development, we have six closely related, major research interests: 1) subtype-specific projection neuron differentiation during neocortical development; 2) induction of subtype-specific neurogenesis (birth of new neurons) from endogenous neural progenitors / “stem cells”; 3) cellular repair of complex CNS circuitry, in particular neocortical and cortical output (e.g. corticospinal, cortico-brainstem circuitry); 4) neural progenitor / stem cell biology; 5) directed differentiation of m/h ES/iPS into subtype-specific neocortical projections neurons; 6) subtype-specific axon guidance controls.



Last Update: 7/7/2014



Publications

For a complete listing of publications click here.

 


 

Magavi SS, Leavitt BR, Macklis JD. Induction of neurogenesis in the neocortex of adult mice. Nature. 2000 Jun 22;405(6789):951-5.

Arlotta P, Molyneaux BJ, Chen J, Inoue J, Kominami R, Macklis JD. Neuronal subtype-specific genes that control corticospinal motor neuron development in vivo. Neuron. 2005 Jan 20;45(2):207-21.

Molyneaux BJ, Arlotta P, Hirata T, Hibi M, Macklis JD. Fezl is required for the birth and specification of corticospinal motor neurons. Neuron. 2005 Sep 15;47(6):817-31.

Ozdinler PH, Macklis JD. IGF-I specifically enhances axon outgrowth of corticospinal motor neurons. Nat Neurosci. 2006 Nov;9(11):1371-81.

Lai T, Jabaudon D, Molyneaux BJ, Azim E, Arlotta P, Menezes JR, Macklis JD. SOX5 controls the sequential generation of distinct corticofugal neuron subtypes. Neuron. 2008 Jan 24;57(2):232-47.

Joshi PS, Molyneaux BJ, Feng L, Xie X, Macklis JD, Gan L. Bhlhb5 regulates the postmitotic acquisition of area identities in layers II-V of the developing neocortex. Neuron. 2008 Oct 23;60(2):258-72.

Azim E, Jabaudon D, Fame RM, Macklis JD. SOX6 controls dorsal progenitor identity and interneuron diversity during neocortical development. Nat Neurosci. 2009 Oct;12(10):1238-47.

Czupryn A, Zhou YD, Chen X, McNay D, Anderson MP, Flier JS, Macklis JD. Transplanted hypothalamic neurons restore leptin signaling and ameliorate obesity in db/db mice. Science. 2011 Nov 25;334(6059):1133-7.

Cederquist GY, Azim E, Shnider SJ, Padmanabhan H, Macklis JD. Lmo4 establishes rostral motor cortex projection neuron subtype diversity. J Neurosci. 2013 Apr 10;33(15):6321-32.

Greig LC, Woodworth MB, Galazo MJ, Padmanabhan H, Macklis JD. Molecular logic of neocortical projection neuron specification, development and diversity. Nat Rev Neurosci. 2013 Nov;14(11):755-69.

Sadegh C, Macklis JD. Established monolayer differentiation of mouse embryonic stem cells generates heterogeneous, neocortical-like neurons stalled at a stage equivalent to mid-corticogenesis. J Comp Neurol. 2014 Mar 8.



© 2014 by the President and Fellows of Harvard College