June 2022: Richard Vallee Lab


What is the main focus of your lab?

Our lab is interested in a variety of biological processes involving microtubules and their associated proteins.  Our initial findings regarded the microtubule associated protein MAP2 as a dendritic marker, which we further identified as the first AKAP (A Kinase Associated Protein) responsible for recruitment of PKA to the dendritic compartment.  We went on to identify cytoplasmic dynein, initially as another brain MAP. It  was the first and is still the predominant  minus end-directed microtubule motor protein known.  It is responsible for retrograde axonal transport, and has important roles in in mitosis, cell migration, growth cone motility, virus transport, and other aspects of neuronal and nonneuronal cell behavior, many of which have been studied in in our lab.

A newer focus of our work involves an additional fundamental role we discovered for cytoplasmic dynein in brain development.  This work began with efforts to understand molecular and cellular basis for the brain developmental disease lissencephaly (smooth brain), which is caused by decreased expression of the cytoplasmic dynein regulatory factor, LIS1.  To test the role of LIS1and dynein  in brain development   we used in utero electroporation  to introduce shRNAs and mutant cDNAs  into live embryonic rat brain, work initially performed by a Ph. D. student in my lab -  Jin-Wu Tsai - , in collaboration with Arnold Kriegstein, then at Columbia.  We co-expressed fluorescent fusion protein markers to monitor changes to cellular and subcellular behavior to understand the specific roles of these factors in the mechanisms of neuronal migration, morphogenesis, and neurogenesis. This work has led to a model for how LIS1 mutations cause lissencephaly (Tsai et al., 2005; 2007, and 2010). The work has also led to models for how the forces generated by cytoplasmic dynein at the nuclear envelope of neuronal progenitors contribute to their migration and division.

A recent focus of the lab has regarded earliest stages of neurogenesis in the CNS, including the unusual and long-mysterious behavior of the radial glial progenitor (RGP) cells, known as INM (interkinetic nuclear migration). The processes of the RGP cells span the entire thickness of the developing cortex from the ventricles to the pial surface of the brain, and serve as guides for migrating neurons.

Equally important, the RGP cells are also highly proliferative and multiply to give rise to most of the neurons and glial cells in the developing brain.  The RGPs exhibit a remarkable form of cell cycle-dependent nuclear oscillation y behavior: the nuclei divide at the surface of the ventricle, ascend "basally" during G1, undergo S-phase, and then return  during G2 to the ventricle to divide again. The physiological purpose and underlying mechanisms for this highly conserved behavior have remained largely unexplored until recently. Our lab found that, whereas  cytoplasmic dynein controls apical INM in the RGP cells, a  specific form of kinesin, known as KIF1A, i s responsible for G1-dependent  basal nuclear migration (Tsai et al., 2010).  KIF1A is also the same gene under investigation at Columbia and elsewhere in conjunction with KIF1A.ORG for understanding and potentially controlling the clinical consequences of Kif1a mutations in children.) 

Other questions of current interest in our lab involve the cytoplasmic dynein accessory factors BicD2 (Bicaudal D2) and RILP the (the Rab-Interacting Lysosomal Protein).  BicD2 is an orthologue of the Drosophila  gene Bicaudal-D, and both the Drosophila and vertebrate gene products act as important cytoplasmic dynein regulatory factors.  We have found that human BICD2 mutations also cause severe brain developmental defects which can be understood in terms of the principles of neurogenesis and migration worked out in our other studies (see above). 

We have also found the long-known protein RILP (Rab7-associated lysosomal protein) to be involved in a novel cellular mechanism to protect against adenovirus infection.  We have since found that RILP plays novel roles in linking cytoplasmic dynein to autophagosomes via direct interactions with LC3 and Atg5.  We found that RILP controls AP transport, and that, RILP expression is regulated by mTOR inhibition and to controls AP transport, but autophagic turnover as well.  Studies are under way in the lab  to understand the full range of roles for RILP roles in autophagy, and more of its physiological and pathophysiological importance.

How long have you had your lab? When did you join Columbia University?

Since 2022

How big is your lab currently?

6 members

Where is your lab located?

VP&S 15-410

Lab management:

How do members of your lab celebrate accomplishments?


Does your lab have any fun traditions?

Dinners at ASCB meetings

What was the most exciting part about starting your new lab?

Many bright students and postdocs


What was the main reason of you joining CSCI? What are the beneficial aspects of CSCI membership for your lab?

Through our work on lissencephaly, microcephaly,  and other brain developmental diseases,  we found the cell biology of neural progenitors to be very exciting, with important implications for resolving multiple basic and classic questions in brain development.

What do you plan to bring to the CSCI community?

We have expanded methods of live in situ imaging of neural  progenitor cell migration, which might begin to answer many other developmental questions.