Dr. Cleveland's laboratory has focused in two major directions. Molecular genetics and cell biology of mammalian chromosome movement and spindle assembly during mitosis: Our interests are in deciphering the mitotic checkpoint, major mechanism in mammals that insures delivery of every chromosome to each daughter cell during mitosis. We use in vitro extracts that can reproduce the cell cycle in vitro as well as gene targeted mice to identify the principles of chromosome segregation. A key aspect of this is defining "what is a centromere". We are using assembly of purified components and molecular genetics in cells and mice to define the nature of this mark. Molecular genetics of axonal growth and motor neuron disease: Using transgenic and gene targeted mice, the principles that support axonal growth are being identified as are ways in which errors in the scaffolding structure within axons lead to disease. Similar approaches are being used to determine mechanisms underlying the inherited forms of the most prominent adult motor neuron disease, amyotrophic lateral sclerosis, or ALS, the hallmark of which is the selective death of motor neurons.
Da Cruz S, Cleveland DW. Understanding the role of TDP-43 and FUS/TLS in ALS and beyond. Curr Opin Neurobiol. 2011 Aug 1.
Vande Velde C, McDonald KK, Boukhedimi Y, McAlonis-Downes M, Lobsiger CS, Bel Hadj S, Zandona A, Julien JP, Shah SB, Cleveland DW. Misfolded SOD1 Associated with Motor Neuron Mitochondria Alters Mitochondrial Shape and Distribution Prior to Clinical Onset. PLoS One. 2011;6(7):e22031.
Polymenidou M, Lagier-Tourenne C, Hutt KR, Huelga SC, Moran J, Liang TY, Ling SC, Sun E, Wancewicz E, Mazur C, Kordasiewicz H, Sedaghat Y, Donohue JP, Shiue L, Bennett CF, Yeo GW, Cleveland DW. Long pre-mRNA depletion and RNA missplicing contribute to neuronal vulnerability from loss of TDP-43. Nat Neurosci. 2011 Apr;14(4):459-68.
Israelson A, Arbel N, Da Cruz S, Ilieva H, Yamanaka K, Shoshan-Barmatz V, Cleveland DW. Misfolded mutant SOD1 directly inhibits VDAC1 conductance in a mouse model of inherited ALS. Neuron. 2010 Aug 26;67(4):575-87.
Ling SC, Albuquerque CP, Han JS, Lagier-Tourenne C, Tokunaga S, Zhou H,Cleveland DW. ALS-associated mutations in TDP-43 increase its stability and promote TDP-43 complexes with FUS/TLS. Proc Natl Acad Sci U S A. 2010 Jul 27;107(30):13318-23.
Lagier-Tourenne C, Polymenidou M, Cleveland DW. TDP-43 and FUS/TLS: emerging roles in RNA processing and neurodegeneration. Hum Mol Genet. 2010 Apr 15;19(R1):R46-64. [REVIEW]