Louis J. Ptácek, MD
	Genetic diseases of muscle, heart and brain and hereditary variation of human sleep behavior
	Email: ljp@ucsf.edu Website: Ptacek Lab
Selected Publications | Complete Publications

Louis J. Ptácek, MD focuses his laboratory on genetic diseases of muscle, heart and brain and hereditary variation of human sleep behavior. His group has cloned genes causing many disease and behavioral phenotypes in humans. In addition, he and his collaborators probe the biology underlying normal function of the encoded proteins in the nervous system and pathophysiology of the mutant proteins in human neurological diseases. Study of these single gene disorders is offering clues to susceptibility genes that may contribute to 'risk' of more common and genetically complex phenotypes like epilepsy, migraine, and normal sleep variation.

Dr. Ptacek pioneered the field of ‘Channelopathies’ that began with the mapping and cloning of a number of genes causing periodic paralysis and non-dystrophic myotonias, symptoms that he proposed as a models for other electrical disorders. More recent work has identified genes causing cardiac arrhythmias, epilepsy, and migraine headache.

He and Dr. Christopher Jones identified and characterized the first human families with a Mendelian circadian rhythm variant. These individuals have an extreme "morning lark" phenotype and they called this variant familial advanced sleep phase syndrome (FASPS). His group, in collaboration with Ying-Hui Fu’s lab, has gone from the clinical and physiologic characterization of this phenotype to the mapping and cloning of the causative genes, biochemical study of the encoded proteins, and generation of animal models. In addition, they have collected a large group of families with FASPS and other circadian sleep disorders, and these are being studied to identify additional genes important for human circadian regulation. This work represents a move from purely ‘disease genetics’ to the genetics of human behavior and will ultimately lead to new insights into the normal function of the human nervous system and mechanisms of disease. Ultimately, such insights will lead to new therapies for treating patients.

In all these cases, there is variation in the expressivity of mutations, even within the same family. While some of this is certainly environmental and epigenetic, it is also likely that the genetic background of each gene carrier is also important. Thus work relelvant to the IRM that is anticipated as techniques are developed will be to inject nuclei from patient cell lines into enucleated ES cells (Somatic cell nuclear transfer). Such cells can then be differentiated into relevant cell types to enable genetic, proteomic, and cell biological studies of relevant cells on the specific patient’s genetic background.

Selected Publications

Plaster NM, Tawil R, Tristani-Firouzi M, Canun S, Bendahhou S, Tsunoda A, Donaldson MR, Iannaccone ST, Brunt E, Barohn R, Clark J, Deymeer F, George AL, Fish FA, Hahn A, Nitu A, Ozdemir C, Serdaroglu P, Subramony SH, Wolfe G, Fu YH, Ptácek LJ. Mutations in Kir2.1 cause the developmental and episodic electrical phenotypes of Andersen's syndrome. Cell. 2001, 105:511-9.

Xu Y, Padiath QS, Shapiro RE, Jones CR, Wu SC, Saigoh N, Saigoh K, Ptácek LJ, Fu YH. Functional consequences of a CKI? mutation causing familial advanced sleep phase syndrome. Nature. 2005;434:640-4.

Padiath QS, Saigoh K, Schiffmann R, Asahara H, Koeppen A, Hogan K, Ptácek LJ, Fu YH. Lamin B1 duplications cause autosomal dominant leukodystrophy. Nat Genet. 2006 Oct; 38(10):1114-23. Epub 2006 Sep 3.

Xu Y, Toh KL, Jones CR, Shin JY, Fu YH, Ptácek LJ. Modeling of a human circadian mutation yields insights into clock regulation by PER2. Cell. 2007 Jan 12;128(1):59-70.

Information last updated April 2007