Jeffrey Macklis

Jeffrey D. Macklis is an American neuroscientist. He is the Max and Anne Wien Professor of Life Sciences in the Department of Stem Cell and Regenerative Biology and Center for Brain Science at Harvard University, Professor of Neurology and of Neurosurgery at Harvard Medical School, and Principal Faculty of the Neuroscience / Nervous System Diseases Program at the Harvard Stem Cell Institute.

Macklis received a dual S.B. in bioelectrical engineering and literature from the Massachusetts Institute of Technology. He received his M.D. and Ph.D. in 1984 from the Harvard–MIT Program of Health Sciences and Technology (HST), where he was advised by Richard L. Sidman. He completed a postdoctoral fellowship in developmental neuroscience with Sidman. Macklis trained clinically in internal medicine at Brigham and Women’s Hospital (BWH) and in adult neurology in the Harvard-Longwood Neurological Training Program.

Macklis first established his laboratory in the Basic Science Division of Neurosciences of Boston Children's Hospital (BCH). In 2002, he moved to Massachusetts General Hospital (MGH), where he was the founding Director of the MGH-HMS Center for Nervous System Repair (2002–2011). He also co-directed the Parkinson's Disease and Related Disorders Program at BWH.

In 2004, Macklis founded the Neuroscience / Nervous System Diseases Program at the Harvard Stem Cell Institute at Harvard University, which he directed until 2013. In 2007, Macklis was appointed the Max and Anne Wien Professor of Life Sciences. His lab moved physically to Cambridge, MA in 2011. He is a faculty member of the Harvard graduate programs in Neuroscience; Biological and Biomedical Sciences; Developmental and Regenerative Biology; and Molecules, Cells, and Organisms; as well as the Harvard-MIT HST program.

Macklis became a Distinguished Investigator of the Paul G. Allen Frontiers Group in 2015. He became a Simons Foundation Autism Research Initiative (SFARI) investigator in 2017.

The Macklis lab studies neural development in the cerebral cortex, with focuses on axon guidance and growth cone biology as well as molecular mechanisms of adult neurogenesis. Macklis's lab has found that the axonal growth cone is semi-autonomous and makes growth decisions locally without constant input from the nucleus in the soma.

In addition to their work on axon growth, the Macklis lab studies neuronal sub-type specification, and how neuronal sub-types may be selectively affected by different neurodegenerative diseases and neurodevelopmental disorders. Specific cell types of interest include the following:

• Corticospinal motor neurons (CSMN), which are lost in spinal cord injury and motor neuron diseases (e.g. amyotrophic lateral sclerosis, hereditary spastic paraplegias, primary lateral sclerosis)
• Corticostriatal projection neurons (CStrPN), which are lost in Huntington's disease and corticobasal degeneration

The Macklis lab studies mechanisms of endogenous regeneration in the central nervous system which can be applied toward regeneration of the brain and spinal cord. The lab performs in vitro culture of embryonic stem cells and induced pluripotent stem cells for the validation of molecular mechanisms of directed neuronal sub-type differentiation, as well as for therapeutic screening of pathways involved in different neurological diseases. Macklis's lab was first to show that callosal projection neurons (CPNs) develop abnormally in Rett syndrome. In 2016, his lab identified the role of aberrant NF-κB pathway activation within CPNs which leads to under-developed dendrites. The Macklis lab is also interested in identifying similar sub-type-specific targets in autism.