Welcome to the Louvi Lab

Our research is generally concerned with the study of molecular mechanisms governing the development of the vertebrate brain. We are particularly interested in addressing how the perturbation of basic biological mechanisms leads to clinically significant brain pathologies. Working closely with other research groups in the Yale Program on Neurogenetics, we study the molecular and cellular mechanisms underlying neurodevelopmental disorders associated with specific genetic lesions. Insight into these questions will shed light on fundamental neurodevelopmental processes and provide information relevant for the design of therapeutic approaches.

Cerebral Cavernous Malformations (CCM)

We are investigating the biology of Ccm3, one of three genes implicated in the pathogenesis of CCM, a monogenic cerebrovascular disorder. We have generated a mouse model that develops vascular lesions highly similar to human cavernomas; its study has led to the identification of cell autonomous as well as cell non-autonomous functions of CCM3 in vascular and neural development, and has unraveled an important role of this protein in the neurovascular unit.

  • Tanriover et al. (2008). PDCD10, the gene mutated in Cerebral Cavernous Malformation 3 (CCM3) is expressed in the neurovascular unit. Neurosurgery 62, 930-938.
  • Chen et al. (2009). Apoptotic functions of PDCD10, the gene mutated in cerebral cavernous malformation 3. Stroke 40, 1474-1481.
  • Louvi et al. (2011). Loss of cerebral cavernous malformation 3 (Ccm3) in neuroglia leads to CCM and vascular pathology. Proc. Natl. Acad. Sci. USA. 108, 3737-3742.
  • Oztürk, Louvi, and Günel (2011). Genetics of Cerebral Cavernous Malformations. In Youmans Neurological Surgery, 6th edition, ed. H. R. Winn, Elsevier.
  • Louvi et al. (2013). Ccm3/Pdcd10, a gene associated with cerebral cavernous malformations, is required for neuronal migration (under review)

Disorders of Cortical Development

Several novel genes implicated in human cortical development have been identified in the Günel lab using genetic analyses and next generation sequencing. We are using in vitro and in vivo approaches to examine the biology of these genes and are characterizing relevant animal models.

  • Bilguvar, Oztürk, et al. (2010). Whole-exome sequencing identifies recessive WDR62 mutations in severe brain malformations. Nature 467, 207-210.
  • Barak, Kwan, et al. (2011). Recessive LAMC3 mutations cause malformations of occipital cortical development. Nat. Genet. 43, 590-594.

To see more about the Gunel Lab click here.


Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy, the most common monogenic form of ischemic cerebral small-vessel disease, is associated with highly stereotypical mutations in the extracellular domain of the Notch 3 receptor. Our recent work has demonstrated that two phenotypically distinct mutations define different hypomorphic activity states of the receptor. Transgenic mice expressing the mutant receptors in vascular smooth muscle cells develop a spectrum of phenotypes that parallel remarkably the human condition. We are currently investigating the molecular and cellular biology of Notch signaling in vascular smooth muscle cells.

To see more about the Artavanis-Tsakonas Lab click here.

Tourette syndrome

Using genetic evidence obtained in the State lab as a starting point, our collaborative work aims at elucidating the biology of SLITRK1 (SLIT and Trk-like family 1), a gene involved in rare cases of Tourette syndrome, a developmental neuropsychiatric disorder. We are using molecular and cell biological approaches as well as animal models to characterize the functions of Slitrk1 in brain development and explore the impact of disease-linked variants on brain morphogenesis and maturation.

  • Abelson, Kwan, O'Roak, et al. (2005). Sequence variants in SLITRK1 are associated with Tourette's syndrome. Science 310, 317-320.
  • Stillman, Krsnik, et al. (2009). Developmentally regulated and evolutionarily conserved expression of SLITRK1 in brain circuits implicated in Tourette syndrome. J. Comp. Neurol. 513, 21-37.